Tailor-Made Self-Assemblies from Functionalized Amphiphiles

Subscriber access provided by University of Florida | Smathers Libraries

Tailor-Made Self-Assemblies from Functionalized Amphiphiles: Diversity and Applications Saheli Sarkar, Pritam Choudhury, Soumik Dinda, and Prasanta Kumar Das Langmuir, Just Accepted Manuscript • DOI: 10.1021/acs.langmuir.8b00259 • Publication Date (Web): 26 Mar 2018 Downloaded from http://pubs.acs.org on March 26, 2018

Just Accepted “Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted online prior to technical editing, formatting for publication and author proofing. The American Chemical Society provides “Just Accepted” as a service to the research community to expedite the dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully peer reviewed, but should not be considered the official version of record. They are citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or consequences arising from the use of information contained in these “Just Accepted” manuscripts.

is published by the American Chemical Society. 1155 Sixteenth Street N.W., Washington, DC 20036 Published by American Chemical Society. Copyright © American Chemical Society. However, no copyright claim is made to original U.S. Government works, or works produced by employees of any Commonwealth realm Crown government in the course of their duties.

Page 1 of 63 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

Tailor-Made Self-Assemblies from Functionalized Amphiphiles: Diversity and Applications Saheli Sarkar, Pritam Choudhury, Soumik Dinda, and Prasanta Kumar Das* Department of Biological Chemistry, Indian Association for the Cultivation of Science Jadavpur, Kolkata – 700 032, India

*Corresponding author: E-mail: [email protected]

1

ACS Paragon Plus Environment

Langmuir 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ABSTRACT The objective of this present feature article is to coalesce our recent advancement on different expressions of tailor-made supramolecular self-assemblies and to explore them as a function of molecular architecture. In last one decade, we have developed a library of elegant and simple functional amphiphilic small molecules, which have very interesting abilities to form diverse manifestations of supramolecular self-assemblies like micelles, reverse micelles, vesicles, fibres, supramolecular gels and so on. Each of the expressions of the self-aggregated structures has their individual prominences and finds important applications in the fields of chemistry, physics, biology and others. In this article, the major emphasis is mostly on how to attain the precise control over the development of various well defined supramolecular selfassemblies through judicious designing of low-molecular-weight amphiphiles. By tuning, only the functional moieties of the amphiphilic structure, diverse supramolecular architectures can be accomplished with task specific applications. We expect that this article will provide a general and conceptual demonstration of various approaches to develop different functional supramolecular systems and their prospective applications in numerous domains.

2


Page 2 of 63

Page 3 of 63 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

INTRODUCTION Supramolecular self-assembly: a spontaneous self-association of small molecular components through intermolecular non-covalent interactions like hydrogen-bonding, hydrophobic interactions, π-π stacking, van der Waals forces, metal-ligand complexation, electrostatic interaction and so on.1-3 The advent of supramolecular chemistry was initiated with the preliminary realization of an enzyme-substrate interaction on the canvas of host-guest system. Development of different manifestations of higher order molecular self-assemblies from simple amphiphilic molecule was one of the on course evolution of supramolecular chemistry.4 The blessing of supramolecular self-assemblies are ranging from the formation of plasma membrane to generation of the genetic information carrier (DNA) where the involved driving forces are primarily non-covalent interactions. Design and development of functionalized amphiphiles with tunable features might play a fundamental role in programming the spontaneous organization of the building blocks under suitable thermodynamic conditions. Structural diversity of the amphiphilic molecules and modes of interactions among themselves in varying medium result in the formation of self-assembled structures like micelles, reverse micelles, microemulsions, liquid crystals, vesicles, fibres, gels and many others.5,6 Each self-assembly has its distinct characteristics and finds potential applications on its own as well as through the formation of a range of soft materials. With the aim to develop well-defined supramolecular self-assemblies, rational designing of lowmolecular-weight amphiphiles has become one of the major thrust of our research activities. The present feature article provides a roadmap towards the advancement in different expressions of self-assemblies through fine tuning of the basic building block. It will emphasize on the recent progress on their synthesis, modifications of structural units by introducing multimodal functionality, facile organization to self-assembly and the structureproperty correlation towards task specific applications. 3


Langmuir 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

SUPRAMOLECULAR

SELF-ASSEMBLIES:

Page 4 of 63

INSIGHT

AND

DESIGNING

PRINCIPLES The term 'supramolecule' was introduced by Karl Lothar Wolf and his co-workers in 1937 to describe hydrogen-bonded dimeric structure of carboxylic acid.7 The key influence of noncovalent interactions in self-assembly started to receive due importance after the double helical structure of DNA that formed due to hydrogen-bonding interaction was established. Consequently, scientists tried to explain different naturally occurring as well as synthetic systems on the basis of this supramolecular concept. Among many fascinating phenomena of supramolecular chemistry, development and understanding of the self-assembled structures formed by amphiphilic molecules (either natural or synthesized) have received noteworthy emphasis and is still continuing. Amphiphiles with a polar head group and non-polar tail are the basic building blocks of supramolecular self-assemblies. Small molecules with balanced functional moieties (hydrophilic and hydrophobic) have the propensity to interact with each other by the combinations of several non-covalent weak forces like hydrogen-bonding, hydrophobic interaction, van der Waals forces and others.1,2,8 Manipulation in the functional moiety of the amphiphiles holds the key to constitution of diverse supramolecular selfassemblies like micelles, reverse micelles, vesicles, fibres, supramolecular gels and so on (Scheme 1). In this feature article, we report designing of amphiphilic molecules with varying hydrophobic moieties linked with different hydrophilic functional motif through linkers like amide, esters, oxyethylene units, and others. Consequently, these large variety of amphiphilic molecules formed different self-aggregated structures depending on the bulk domain. Development of self-assembled soft materials owing to the supramolecular organization of simple amphiphilic molecules has immense potential to be utilized across the scientific domain.9-14

4


Page 5 of 63 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

SUPRAMOLECULAR SELF-ASSEMBLES AND THEIR APPLICATIONS. Micelles. Water has its distinct influence in the formation of self-assemblies in nature while we look for structural motifs to make amphiphiles which will provide a wide range of self-assemblies in different media. Diverse self-assembled structures are known to evolve upon interaction of water with other molecules by the involvement of different intermolecular non-covalent forces. Micelles are the simplest form of self-assembled structures. Micelles or oil-in-water microemulsions formed by dissolution of amphiphiles/surfactants with hydrophilic ‘head’ and hydrophobic ‘tail’ in such a way that the polar heads get solubilized in bulk water and the hydrophobic tails are directed away from water thus forming an oil/water interface with high curvature.15 The formation of micelles is observed above a certain concentration of the surfactant, called critical micellar concentration (CMC). This micro-heterogeneous micellar media has the ability to solubilize water-insoluble organic substrates in its hydrophobic core and amphiphilic molecules at the micellar interface by exposing their polar part to bulk water.16 The anisotropic domain of micelles allows the solubilization of substrates with varying polarity within micelles and thereby increases the possibility of interactions between substrates/reactants at the micro-heterogeneous interface. Consequently, the interfacial concentrations of substrates

becomes higher than the bulk concentration.17 Also, the

activation energy might get decreased because of enhanced collision between reactants at the micellar interface within the range of few angstroms. Moreover, this self-assembled structure offers unique and potential alternative to conventional methods of carrying out organic transformations. To this end, an easy procedure was developed for the reduction of esters utilizing only sodium borohydride in aqueous self-aggregates of cationic surfactants, which is otherwise not possible under ambient condition without the help of other supporting agents or excess of 5


Langmuir 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

reducing agents (Figure 1a).18 Aqueous cationic micelle was used for the reduction of esters with varying hydrophilic-lipophilic balance (HLB) by NaBH4 owing to the proximity of reactants at the micellar interface (1a-f, 2, Chart 1). HLB plays a key role in determining the solubilization site of a substrate within the micellar aggregates. In case of hydrophobic substrates like n-hexylbenzoate (1a), solubilization might have taken place within the deep inside of hydrocarbon-like core of micelles. Consequently, only 27% of reaction yield was noted due to the limited access of ester group to the reductant BH4- ions. To investigate the influence of HLB on the localization of substrate and thereby on the efficiency of reduction, polar substitutions were introduced in the aromatic moieties. As to our expectation, a marked (47-84%) enhancement in yield was noted for -OH- and -NO2-substituted esters (1b,c) along with esters comprise of extended aromatic ring like naphthalene (1f, 80%) and anthracene (2, 80%).On the contrary, a noteworthy decrease in reaction yield was found in case of NHCOCH3- and -Cl-substituted esters (1d, e), where hydrophobicity plays the dominant role. Moreover, the efficiency of the ester reduction was significantly improved in the aqueous cationic micelles of surfactants containing bulky head groups. The second-order rate constants get enhanced with augmentation in the dimension of hydrophilic head (Ltryptophan moiety) most probably because of the better electrostatic interaction between the head groups and substrates. With the motivation of executing enantioselective reaction, micelles could be exploited through the use of appropriate chiral surfactants. Dasgupta et al. provided an idea about utilizing the aqueous micellar aggregates of dipeptide based cationic surfactants having chiral counterion for asymmetric resolution in ester reduction (Figure 1b).19 Different amphiphiles comprise of L-amino acid (L-alanine, L-phenylalanine, L-tryptophan), peptides and gemini surfactants having chiral counterion (L-lactate, L-tartrate, L-quinate) were synthesized (3a-c, 4a-b, 5a-c, Chart 1). The difference in the amphiphile's structure due to 6


Page 6 of 63

Page 7 of 63 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

the variation in head group has its influence on the microstructural parameters of selfassemblies. The supramolecular self-assemblies of these surfactants was exploited towards chiral resolution in reduction of esters by NaBH4. In the micellar solution of N,Nʹdihexadecyl-N,N,N,Nʹ-tetramethyl-N,Nʹ-ethanediyl diammonium diquinate (5c), formation of (R)-2-phenylpropan-1-ol was noted with enantiomeric excess of 53% upon reduction of nhexylester of 2-phenylpropionic acid by NaBH4. Furthermore we showed the modulation in the induced supramolecular chirality owing to the self-assembly where the molecular chirality of basic building block has been tuned by changing the head-group geometry of the amino acid (L-alanine, L-phenylalanine, L-tryptophan) based C16 long chain containing chiral cationic surfactants (3a-c).20 The changes in the aggregate morphology with the structural modification of chiral surfactants get expressed in the respective circular dichroism spectra due to the variation in supramolecular chirality. The molecular origin of supramolecular chirality at the micellar interface has been substantiated both by theoretical and experimental approaches.2,19,20 This supramolecular chirality was exploited toward stereoselective reduction of pro-chiral ketones. To the best of our knowledge, the observed enantiomeric excess (41%) in aqueous micelle of (S)-proline containing surfactant (3d, Chart 1) was found to be the highest for ketone reduction within micelles (Figure 1c). Reverse Micelles. Both Micelles and reverse micelles are well known examples of geometrically bounded supramolecular structures. Reverse (or inverted) micellar aggregate or water-in-oil (w/o) microemulsion can be described by a water droplet that is bounded by surfactants whose hydrophobic tails are protruded toward bulk apolar solvent and hydrophilic heads toward the aqueous core, known as water-pool.21 These macroscopically homogeneous nanometer scale colloidal systems comprise of an anisotropic interface that separates the polar aqueous part 7


Langmuir 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

from the continuous organic phase.22 Potential applications of these w/o microemulsions are widespread due to the augmented area at the interface and capability to solubilize substrates of varying polarities. The water pools have been extensively utilized in diverse applications such as nanoparticle synthesis, enhancing the rates of chemical reaction, confinement of biological water due to its compartmentalization ability.23-25 Biomolecules like proteins, enzymes and nucleic acids are reported to be encapsulated within the water-pool of reverse micelles without affecting their activities.26 Formation of reverse micelle is mainly regulated by the amphiphile's structure and presence of co-surfactant (if required). W0 ([water]/[surfactant]) is the most important micro-structural parameter of w/o microemulsion. Another parameter, z (z = [cosurfactant]/[surfactant]), also has significant importance to the stability of reverse micelles.22Consequently, w/o microemulsions of different sizes were prepared by tuning these micro-structural parameters .27 Additionally, different structural components of surfactants have been altered along with the inclusion of nanomaterials of comparable dimension within reverse micelles to modulate the catalytic efficiency of different enzymes. Catalytic activity of lipase on ester hydrolysis is significantly higher in a bis-(2ethylhexyl)sulfosuccinate sodium salt (AOT) based w/o microemulsions compared to that in cetyltrimethylammonium bromide (CTAB) based reverse micelles.28 Enzyme activity obviously depends on the factors like local molar concentration of water and other ions present in vicinity of the biocatalyst. Moreover, the second-order rate constant (k2) for the Chromobacterium viscosum (CV) lipase-catalyzed hydrolysis of

8


Page 8 of 63

Page 9 of 63 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

O O

OH

CnH2n+1 Lipase

CnH2n+1COOH

H 2O NO2 n = 5 or 7

(1)

NO2

p-nitrophenylcaproate/p-nitrophenyl-n-octanoate (equation 1) was found to be essentially similar across the wide range of W0 in CTAB w/o microemulsions (k2 = 324 ± 13 cm3g-1s-1, at the lowest n-hexanol content, z = 4.8). Concurrently, the water concentration at the interface of CTAB/isooctane/n-hexanol/water w/o microemulsion was reported to be almost unchanged (28.1-31.8 M) across the wide range of W0 (12-44).29 The unaltered interfacial water content may be considered as the reason for the unchanged activity of lipase. Also the meagre water content (almost half of the bulk water concentration) is possibly responsible for the plummeted lipase activity in CTAB reverse micelle.30 Polarity, Size and Flexibility of Head Group: Effect on Lipase Activity within Reverse Micelle. We were able to significantly improve the CV-lipase activity in cationic w/o microemulsions of newly developed surfactants by substituting the methyl groups of CTAB with varying number of hydroxyethyl groups at the polar head (Figure 2a).30 These hydroxyethyl groups, comprise of H-bond donor-acceptor atoms at the head group of cationic surfactants, probably increased the local water concentration at the interface of reverse micelles (6-8). Consequently, hydrolytic activity of lipase steadily improved with enhancement in the number of hydroxyethyl groups in the polar head of surfactant. The activity of lipase in cationic reverse micelle of tris(hydroxyethyl) containing surfactant (8) attained a level (k2 = 582 ± 9 cm3g-1s-1), which is analogous to the result obtained from AOT-based systems (k2 = 654 ± 8 cm3g-1s-1).28 9


Langmuir 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

At this point, the issue intrigued us that along with the possible enhancement in water content, the interfacial area of reverse micelles also simultaneously increased by the inclusion of hydroxyethyl group instead of methyl group at the polar head. Hence, we became curious to know whether the head-group size of surfactants or the water concentration at the interface played the key role in boosting the catalytic efficiency of lipase.31 The lipase activity was measured in the reverse micelles of cationic surfactants with varying head-group size and hydrophilicity (Figure 2b). A number of surfactants were synthesized by successive substitution of three methyl groups of CTAB with hydroxyethyl (6-8), n-propyl (9-11) and methoxyethyl (12-14) groups, respectively. Hydrophilicity at the polar head gets reduced from hydroxyethyl to n-propyl substitution, while the head-group area per surfactant (Amin) remains more or less same for comparable head-group substitution for both series of surfactants (Table 1). Interestingly, the lipase activity was almost comparable in the reverse micelles of complementary analogues of both hydroxyethyl to n-propyl substituted surfactants in spite of their notable difference in the hydrophilicity. Amin is distinctly higher in case of methoxyethyl substituted surfactants (Amin = 2.90 ± 0.05 nm2 for trismethoxyethylated surfactant) in comparison to respective hydroxyethyl and n-propyl substituted head group (Table 1). The lipase activity was also markedly higher in w/o microemulsions of methoxyethyl substituted surfactants (k2 = 1290 ± 12 cm3g-1s-1 for trismethoxyethylated surfactant at W0 = 32-44, z = 2.9) compared to hydroxyethyl and n-propyl substituted surfactants. The catalytic efficiency of lipase noticeably increased with the size of head-group size despite its hydrophilic nature due to the augmentation of “space” in vicinity of enzyme. Head-group size/area of surfactant is playing the dominant role over its hydrophilicity. Enhanced local concentration of enzyme and substrate along with the possible flexibility in enzyme conformation in the increased space at reverse micellar interface might have led to the higher efficiency of lipase (Figure 2b). To the same end, Mitra et al. showed 10


Page 10 of 63

Page 11 of 63 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

that enhancement in the interfacial area not only depends on the large polar head of surfactant but also on the flexibility of the head-group substitution.32 Lipase activity was measured in the reverse micelles of a series of C16 long chain based cationic surfactants with varying head-group with respect to its flexibility/rigidity, size/area, and hydrophilicity (6-11, 15-18, Chart 1). Initially, lipase activity increased with the increment in Amin due to the substitution of bulky tert-butyl moiety (15) at the hydrophilic head-group (Table 1). However, when the CH3 moiety of tert-butyl group successively substituted with -CH2OH (16-18), the enzyme activity was found to be almost similar in spite of enhancement in hydrophilicity at interface. Concurrently, the Amin for tert-butyl as well as its analogous three -CH2OH substituted surfactants was found to be comparable which is possibly originated from the rigidity of surfactant’s head-group (Table 1).The lipase activity notably enhanced for surfactants with the hydroxyethyl substituted polar head (6-8) with concurrent increase in the number of hydroxyl group and Amin due to the flexibility of the head group. Hence, despite having similar hydrophilicity, the geometric constraints at the surfactant’s head group have a major influence in improving the activity of lipase through variation in interfacial area. Inclusion of different nanomaterials: Effect on Lipase Activity within Reverse Micelle. Augmentation of space in vicinity of enzyme by tuning other parameters like hydrophobic tail length, nature of counterion, inclusion of non-ionic surfactants also facilitated in improving the lipase activity (2-3 fold compared to that observed in CTAB reverse micelle) in cationic reverse micelles. Designing and synthesizing amphiphiles with varying structures is obviously not a trivial task. Consequently, we had to opt an alternative method to tune the microscopic domain of w/o microemulsion prepared from easily available surfactant like CTAB instead of amphiphiles that were synthesized through tedious methods. Herein, we intended to include exogenous agents having comparable dimension that of water11


Langmuir 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

pool/interface, which can increase size/area in vicinity of enzyme localization site. We have chosen the most ever used nanomaterial, gold nanoparticles (GNPs) for doping within CTAB/water/isooctane/n-hexanol reverse micelles without disturbing the stability of reverse micelle.33 Maiti et al. from our group showed the specific role of size and concentration of GNPs on the lipase activity encapsulated within w/o microemulsion.33 In general, improvement in lipase activity was noted in for GNP-doped CTAB w/o microemulsions with increasing concentration (0-52 µM) and size (3-30 nm) of GNPs. The observed catalytic efficacy of lipase in GNP-included CTAB w/o microemulsions ([GNP]: 52 µM, 20 nm) is 2.5-fold higher compared to that in native CTAB reverse micelle. Although, lipase gets structurally deformed as well as deactivated upon interacting with GNPs in aqueous media but it showed improvement in its activity within GNP-doped reverse micelles. Inclusion of GNP within the water pool of CTAB reverse micelle (5.2±0.5 nm at z = 11.2) and the aggregation of surfactants and water around GNP ('GNP pool') instead of only water led to the formation of large (58±6 nm at z = 11.2) reverse micelles (Scheme 2). Depending on the size of nanoparticles, number of GNP will be localized within water pool of a reverse micelle. Smaller sized GNP will not cause any change in the overall size of reverse micelles and hence will not affect the interfacial area and thereby the lipase activity. Larger sized GNP localizes itself at the water pool of reverse micelle resulting in increase of water pool size and the interfacial area. Consequently, lipase located at the enlarged interface of the GNPincluded w/o microemulsions exhibited improvement in its activity due to the flexibility in enzyme conformation as well as enhancement in enzyme and substrate concentrations. Larger is the size of GNP, greater is the enzyme activation.

12


Page 12 of 63

Page 13 of 63 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

Furthermore, we planned to include gold nanorod (GNR) within reverse micelles as the surface area of GNR would be higher than that of spherical GNPs having same volume.34 We synthesized GNR of different aspect ratio (2.5 ± 0.3, 3.0 ± 0.2, 3.5 ± 0.2, respectively, having a width of 10 ± 1 nm) using HAuCl4, ascorbic acid, CTAB, NaBH4. These GNRs doped CTAB w/o microemulsion had large interfacial area and ability to solubilize more amount of water (Scheme 2). So, lipase encapsulated within this GNR doped CTAB reverse micelles (W0 = 52-56, z = 4.0) showed striking enhancement in its activity (k2 = 1488 ± 11 cm3g-1s-1 at 52 µM of Au), which was ~3.5 and 2.5-fold higher compared to the lipase activity in CTAB and AOT based reverse micelles, respectively. Beside GNPs, we also made use of single walled carbon nanotube (SWNT), whose diameter (1-5 nm) is comparable to the interfacial thickness of reverse micelles. Ghosh et al. reported the covalent functionalization of

SWNT

to introduce varying

extent of

hydrophilicity to its surface.35 These functionalized SWNTs (f-SWNTs) with varying degrees of hydrophilicity by means of quaternized ethylene diamine, 6-amino caproate, quaternized (ethylenedioxy)bis (ethylamine) and PEG unit were incorporated within CTAB reverse micelles without affecting the stability of nanohybrids. f-SWNT using 6-amino caproate was found to be appropriately located at the interface of reverse micelles (Scheme 2) possibly because of its optimum hydrophilicity. CV-lipase, entrapped at this augmented interface of fSWNT-containing CTAB w/o microemulsions showed significant improvement in its activity (2.5-fold) from 433 ± 7 (in absence of nano-constructs) to 1074 ± 10 cm3g-1s-1 at 1.0 µg mL-1 of nano-construct. Concurrently, the enhancement in the flexibility of lipase conformation within f-SWNT integrated reverse micelle was substantiated by circular dichroism and FTIR spectroscopy.

13


Langmuir 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 14 of 63

To maximize the influence of 'space' on lipase activity, Mandal et al. reported the development of w/o microemulsion doped with nanocomposite comprise of GNP-decorated SWNT

(Scheme

2).36

Non-covalently

dispersed

SWNT

cetylalaninetrimethylammonium chloride (CATAC)) was mixed with

(using

CTAB,

trisodiumcitrate

capped GNP to develop SWNT-GNP composite through counterion exchange. This SWNT– GNP nanocomposite incorporated reverse micelle was used to boost the lipase activity. Catalytic efficiency of CV-lipase encapsulated within this self-assembled nanocomposite enhanced up to 3.9-times (k2 = 1694 ± 16 cm3g-1s-1) compared to standard CTAB reverse micelle. Furthermore, we investigated the alteration in the structure of w/o microemulsion using surface functionalized carbon dots (CDs) instead of GNPs.37 Citric acid was utilized as precursor of the carbon core while sodium-salt of glycine (NaG), glycine (G), sodium-salt of 11-aminoundecanoic acid (Na-Aud), 11-aminoundecanoic acid (Aud), and n-hexadecylamine (Hda) were utilized to functionalize the surface of CDs having average size of 5-7 nm. The hydrodynamic diameter of CTAB w/o microemulsion (CTAB/isooctane/n-hexanol/water, z = 6.4 and W0 = 44) was found to be 15-20 nm. Inclusion of hydrophobic CD-Aud and CD-Hda increased the dimension of w/o microemulsions to 120-200 nm. Micellar exchange dynamics and rearrangement of the self-aggregates possibly enhanced the size of reverse micelles through hydrophobic interaction between CTAB and surface functionalizing agent of CDs (Scheme 2). The activity of CV lipase entrapped within CD-Aud and CD-Hda included reverse micelles exhibited 3.7-fold and 3.4-fold improvement in its activity. Regulation of Activity of enzymes other than Lipase within Reverse Micelle. In addition to CV-lipase, we have also made attempt to modulate the activity of other surfaceactive enzymes like horseradish peroxidase (HRP) and soybean peroxidase (SBP). We 14


Page 15 of 63 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

reported the striking activity of hydrophobically adsorbed peroxidase onto SWNTs in the cationic reverse micelles by measuring the initial velocity (V) of pyrogallol to purpurogallin oxidation by enzymes.38 Adsorption of HRP and SBP onto SWNTs resulted in the loss of its secondary structure and catalytic activity in water. Interestingly, the structurally and functionally deformed enzyme-SWNT exhibited ∼7-9- fold enhancement in activity (V = 131 ± 2 µM/min) in CTAB reverse micelles with varying W0 and z compared to that was in water (Figure 2c). The observed activity was ∼1500-3500-foldhigher compared to the observed activity in aqueous-organic biphasic mixtures. Peroxidase-SWNT located possibly at the micellar interface might have facilitated the transport of substrates across the interfacial domain that led to the remarkable improvement in the peroxidase activity (Figure 2c). An overall enhancement in the peroxidase activity was noted within the w/o microemulsions amphiphiles having larger head-group size. Hence, positioning of peroxidase-SWNT at the augmented interface of w/o microemulsion is the prime cause for its superior activity. Vesicle. Liposomes or vesicles, another fascinating class of supramolecular self-assemblies, are the poly-molecular association of amphiphilic molecules aided by simple non-covalent forces. The lipid vesicle was first reported by British haematologist A. D. Bangham who named it as spherulites.39 Besides phospholipids, small amphiphilic molecules with a polar head group and twin chains hydrocarbon are suitable for formation of bilayered vesicle having an aqueous compartment inside and bulk aqueous domain outside with a hydrophobic layer in between them.40 Formation of vesicle by different amphiphilic molecules (single/twin chained, polymeric, phospholipids) as well as its mechanism of formation have been welldocumented.39-42 The distinct structure of vesicle with hydrophobic bilayer and an inside water pool is suitable for solubilizing both hydrophobic as well as hydrophilic cargos. This 15


Langmuir 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

membrane mimetic system has huge prospects as cellular transporters in gene therapy, drug delivery.42 Herein, we will present formation of vesicular self-assemblies in our laboratory by simple functional amphiphilic molecules and their prospective applications. In this regard, Shome et al. reported the formation of bilayered vesicles by mixing of amino acid functionalized cationic surfactants (3a-c) with anionic surfactants such as sodium dodecylbenzene sulfonate (SDBS) and sodium dodecyl sulfate (SDS)).43 Vesicular selfassociation was mainly guided by the HLB of both cationic and anionic surfactants. Considering the cargo carrying ability of the vesicles, we tested its cytocompatibility, one of the prerequisites of delivery vehicle. According to MTT assay, these catanionic bilayered vesicles were found to be enough biocompatible towards NIH3T3 cells indicating their prospect in cellular transportation. In another work, Dinda et al. from our group reported the development of vesicular self-assembly (Figure 3a) by C3 symmetric trimesic acid (TMA) based amino acid functionalized triple tailed amphiphiles (19a-b, Chart 2).44 One of the triskelion amphiphiles with a neutral side chain (triethyleneglycol monomethyl ether, 19a) self-aggregated into vesicle in DMSO-water (2:1 v/v) having average diameter of 250-300 nm (Figure 3b,d), while the ammonium side chain (2,2’-(ethylenedioxy)bis(ethylamine) unit with free –NH3+ at the terminal) decorated another amphiphiles (19b) formed vesicles in pure water (average diameter size = 100-150 nm, Figure 3c,e). The unique structural skeleton of these amphiphilic molecules having an aromatic centre and hydrophilic side chains (three) might have facilitated an interlamellar arrangement of their aromatic domain, while hydrophilic terminals (three) were oriented toward the aqueous domain. The H-type aggregation (face-toface stacking, Figure 3a) of these amphiphilic molecules led to the formation of monolayered vesicles, by which is different from traditional twin-chain phospholipids based bilayer 16


Page 16 of 63

Page 17 of 63 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

vesicles. The self-aggregation phenomena that led to the formation of monolayered vesicles have been validated by UV-vis, fluorescence anisotropy, time resolved study and XRD spectroscopy. Hydrophobicity within the microenvironment of monolayered vesicles is less compared to that in bilayer phosphocholine vesicles. The detail self-assembling mechanism of triskelion amphiphiles revealed that hydrophobic interaction as well as π-π stacking plays the crucial role during the formation of these monolayered vesicles. Fluorescent dye calcein was encapsulated within these vesicles with loading efficiency of ~65-85%. The synthesized vesicle in water was successfully utilized to deliver the loaded anticancer drug, doxorubicin inside the mammalian cells. After the successful construction of vesicular self-assemblies by triskelion amphiphiles, we made attempt to explore it as an efficient cellular transporter. Vesicles/liposomes are designated as most suitable drug-delivery vehicle with considerable cargo loading ability, excellent cytocompatibility, and biodegradability.45 Nevertheless, their fast elimination from blood circulation through reticuloendothelial system as well as lower efficiency to enter into the targeted cells are the major drawbacks.46 On the other hand, SWNT, the pseudo one-dimensional allotrope of carbon, has also emerged as a smart cellular transporter due to its superior ability to translocate through the plasma membrane.47 However, the major hurdles of using SWNTs as a delivery vehicle are poor cargo loading ability and inherent cytotoxicity.48 Amalgamation of these two delivery vehicles would be beneficial to develop a better delivery tool by avoiding their individual limitations. Herein, Dinda et al. developed a vesicle-SWNT conjugate by simple boronic acid-diol covalent linkage between a self-assembled monolayered vesicle and aqueous dispersion of SWNT (Figure 3f).49 Trimesic acid based phenylboronic acid appended triple tailed amphiphiles (19c,d, Chart 2) was used for the formation of monolayered vesicles and aqueous dispersion of SWNT was prepared with cholesterol-based glucose-functionalized amphiphile. These two 17


Langmuir 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

different supramolecular self-assemblies were combined through covalent linkage by using a boronic acid-diol interaction between a phenylboronic acid based monolayered vesicle and 1,2-diol moieties of glucose tethered dispersing agent. Lewis acid-base chemistry was exploited to construct this boronate-diol adduct which can simultaneously hold both vesicle and SWNT leading to the formation of vesicle-SWNT conjugate (Figure 3f-h). Anticancer drug doxorubicin was loaded on this conjugate with a higher capacity (67%) compared to the individual cargo carrier (vesicle or CNT). This cytocompatible soft-nanocomposite exhibited efficient cellular transportation ability of the loaded doxorubicin. Consequently, this was reflected in a better killing efficacy (71%) of the cancer cells by this vesicle-SWNT conjugate compared to the drug-loaded vesicle or CNT (Figure 3i). A simple synthetic procedure and facile combination of supramolecular self-assemblies led to the successful development of vesicle-CNT conjugate The improved proficiency in cellular transportation of this softnanocomposite with a regulated dose of loaded drug paved the innovative pathway for developing smart delivery vehicle. Along with the formation of vesicular self-assemblies, we also made attempt to develop stimuli responsive supramolecular self-assemblies by low-molecular-weight amphiphiles with precise control over hierarchical self-aggregated structures. Importantly, formation of diverse self-aggregated architectures from same scaffold would be beneficial for task specific applications. Mandal et al. reported the solvent triggered morphological transformation of cholesterol based glucose appended amphiphiles (20,21, Chart 2) and also enroute its structural modification for the formation of higher order aggregates.50 These stimuli responsive amphiphiles get associated to form bilayer vesicles in aqueous medium and transform to supramolecular gels in various mixed and organic solvents. In DMSO-water solvent system, the gradual changes in the morphology of self-assemblies varied from vesicle-to-fibre due to steady change in solvent polarity (Figure 4a-d). Mechanistic 18


Page 18 of 63

Page 19 of 63 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

investigation revealed that morphological transition took place via fusion, elongation and twisting of the self-assemblies owing to the change in orientation of amphiphiles from H-type to J-type arrangement primarily based on the polarity of the solvent systems (Figure 4e). Along this, hydrogen-bonding and solvophobic interaction were also involved in the nanoribbon formation that led to the development of fibrillar network (Figure 4d). This work showed a novel approach to develop solvent-induced vesicle-to-fibre transformation from same molecular backbone, a facile pathway of forming hierarchical self-assembly. Supramolecular Gel. The exploration of supramolecular self-assembly through “bottom-up” approach has offered researchers an elegant strategy for developing a range of materials for diverse applications including drug delivery, sensors, template materials, and so forth.12,51-53 One of such beautiful manifestation of self-assemblies is supramolecular gel. A gelator has the ability to restrict the mobility of a free flowing solvent due to the formation of a semisolid phase by the addition of minute amounts of it. Gels are categorized on the basis of bonding/forces within the entangled network, either being covalent (polymeric gels) or non-covalent (molecular gels).54,55 The supramolecular gels made of low-molecular-weight gelators (LMWG) are finding notable importance because of its quick response to external stimuli, thermoreversibility, and probable biodegradability.55 The non-covalent interactions (e.g., electrostatic, π-π stacking, dipole-dipole, and hydrogen-bonding) hold the LMWG molecules together which provide many benefits over polymer gels.9 An optimal balance of hydrophilicity and hydrophobicity plays the key role in gelation, which could be easily tuned by a small alteration in the amphiphile's structure.9 Supramolecular gels are mainly classified into two major classes: organogel (immobilization of organic solvents) and hydrogel (immobilization of aqueous medium).9,56 We introduced peptide based specially amino acid 19


Langmuir 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

tethered low-molecular-weight amphiphilic gelators, that can be synthesized with ease on large scale. In particular, we showed structure-property correlation of these tailor-made functionalized gelators and summarize their applications. Dipeptide Based Low-Molecular-Weight Organogelators: Phase-selective Gelation. Phase selective gelation by addition of low-molecular-weight organogelators is an efficient tool to wipe out huge amount toxic materials such as dye, petroleum oil from water. Bhattacharya and co-workers first showed selective gelation of oil from oil/water mixture by using a free carboxylic end tethered L-alanine based gelator.57 It seemed that the presence of L-alanine alone is good enough for attaining the suitable HLB for the amphiphile to be a gelator. However, development of multimodal functionalized gelator molecules with versatile gelation ability may be explored in diverse applications. In this context, Kar et al. have developed amphiphilic dipeptides based organo/hydrogelators having free carboxylic end at the C-terminus and long alkyl chain linked at the N-terminus (22a-f, Chart 2).58 Influence of amino acid moiety in gelation was investigated by using varying combinations of aliphatic/aromatic residue substituted amino acids within the structure of amphiphilic gelators. Amphiphiles comprised of tryptophan (22a/b) and phenylalanine (22c/d) exhibited superior gelation

having minimum gelation concentration (MGC) ∼0.45-0.7% (w/v) in

different organic solvents. These dipeptide based amphiphilic gelators selectively immobilize organic solvents from their mixtures in water and the respective xerogels purified wastewater by time-dependent adsorption of organic dyes like crystal violet. Interestingly, the efficient pH-sensitivity of these gelators was

exploited for phase selective gelation of either of the

solvents in a biphasic oil/water mixture. The dissimilarity in the pH-responsive gelation of the acid and its salt was further utilized for treating wastewater by the instant removal of dyes. Development of dipeptide based small amphiphiles devoid of free carboxylic group at 20


Page 20 of 63

Page 21 of 63 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

the C-terminus is also a tricky task. Debnath et al. designed dipeptide based (e.g., Lphenylalanaline/alanine) organogelators (23a-c, Chart 2) by the alteration of alkyl chain length from C-12 to C-16 having MGC of 6-0.15% (w/v) in aromatic solvents.59 Interestingly, these amino acid tethered organogelators are also capable of gelating aromatic solvents selectively from their mixtures with water (Figure 5a). Respective xerogels are also equally efficient in adsorbing dyes (crystal violet, rhodamine 6G) from water (Figure 5b,c), which is useful for treating wastewater. Hence, by regulating the structures of amphiphiles or by changing the pH of the medium, the gelators would find importance in treating oil spills as well as wastewater for green environment. Low-Molecular-Weight Hydrogelators: Potential Applications. Hydrogel has the ability to immobilize huge amount of water within its network and in recent years it is finding noteworthy importance as soft materials owing to its potential applications across the scientific domain.51 In general, hydrogels are composed of natural polymers (e.g., collagens, polysaccharides) and also prepared from hydrophilic synthetic polymers [e.g., poly(acrylic acid) derivatives and polypeptides].60,61 Among many small molecular gelators, peptide based low-molecular-weight hydrogelators (LMWHs) are finding notable importance due to their prospective biomedicinal applications including drug delivery, tissue engineering, cell culture, and potential biocompatibility.51 Nevertheless, non-covalent intermolecular associations within the three-dimensional (3D) network of LMWHs made them more preferable over the polymeric gels particularly in biomedicine due to their thermoreversibility and quick response to external stimuli.61,62 Initially, we wanted to realize the role of polar head groups in controlling the gelation ability of amphiphilic hydrogelators. L-tryptophan containing surfactant molecules (24a-b, Chart 2) having quaternary ammonium group as polar end were designed which are able to form hydrogel in plain water at very low MGCs.63 21


Langmuir 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 22 of 63

Optimal HLB helped the amphiphiles to arrange them in such a fashion that a favourable hydrophobic interaction as well as intermolecular H-bonding get facilitated during the process of self-aggregation. Besides the influence of the head group in the process of gelation, the hydrophobic end also could be an integral part to regulate the self-aggregation. According to the previous reports, hydrophobic interaction along with H-bonding play the key role in hydrogelation.9,63 To understand the influence of alkyl chain of amphiphile in hydrogelation, Roy et al., tuned the hydrophobic end by changing the chain length from C-10 to C-18 of L-tryptophan based amphiphiles (25a-e, 26, Chart 2) keeping the polar end fixed. A minimum C-12 chain length (25b) is essential for imbibing of water and with further increase in the chain length stable gel formation takes place with lower MGCs.64 The amide bond, which is prone to be hydrolysed by base or enzyme,

enhances the potential

applications of this self-aggregated soft materials in biomaterials and biomedicine. The best ever catalyst available in the nature is enzyme. It has the intriguing ability to accelerate number of reactions mostly in aqueous domain with a very high proficiency and selectivity. However, activity of enzymes gets reduced in organic solvents due to their structural deformation and insolubility. To overcome this hurdle, immobilization of enzyme had been attempted in a matrix where it could retain its structural integrity and mass transfer (substrate and product) can easily take place across aqueous/organic interface.18 Supramolecular self-assemblies possess such requisite conditions where optimal combination of hydrophobicity /hydrophilicity offers an enzyme friendly environment as observed in reverse micelles.29 In case of self-assemblies like hydrogel, improvement in enzyme activity was considered to be due to the cooperative effect of the gel network of amphiphilic nanofibers that facilitates mass transfer across the interface. Das et al. from our group reported the immobilization of heme proteins and enzyme within hydrogels of amino acid/peptide based amphiphilic gelators (25d, 27, Chart 2) having long chain and quaternary 22


Page 23 of 63 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

ammonium as hydrophobic and hydrophilic end, respectively.65 Proteins/enzyme entrapped within hydrogel exhibited distinct enhancement in its activity upon dispersion in organic medium. The activation effect (ratio of the activity of the hydrogel-entrapped enzyme in organic solvent to the activity of the native enzyme in water) of cytochrome c enhanced up to 350-fold with variation in the concentrations of protein and gelator. Moreover, hemoglobin and horseradish peroxidase (HRP) entrapped within hydrogel exhibited marked improvement in its activity. Modification in the supramolecular network owing to the alteration in the gelator's structure led to the formation of larger interstitial space which resulted in a higher activation of protein immobilized within networks of amphiphilic molecules. The possible reasons for this striking activation of hydrogel-entrapped proteins are seemed to be followings: i) access of water-soluble substrates to the enzyme is facilitated by the hydrophilic domain of the networks of amphiphilic molecules; ii) the networks of amphiphilic molecules facilitate the formation of an interface between hydrophilic and hydrophobic

domains through which reactants and products are easily transferred; iii) surfactant gelators stabilize the gel matrix into small particles in organic solvent resulting in enhancement of overall surface area that facilitated the mass transfer. Importantly, in the presence of nongelating anionic surfactants, the protein/enzyme activation was dramatically improved up to 675-2000 fold due to disintegration of the gel into further smaller-sized particles. Along with the formation of various kind of self-assembled structures and its immobilization ability, we also made attempt to develop innovative way to dissipate such self-aggregates so that it can be exploited in different applications ranging from biocatalysis to biomedicine. Keeping this issue in our mind, two complementary hydrogels were developed using cholesterol based phenylboronic acid and glucose tailored amphiphiles (21, 28, Chart 2). These two gels having complementary functional moieties (boronate and diol) degrade upon mixing because of the formation of a boronate-diol adduct.66 Transformation 23


Langmuir 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

from a self-aggregated structure to a non-self-assembled one took place through the formation of the boronate-diol adduct, which lacks any self-assembling property (Figure 6ag). The mutual self-destruction of these complimentary gels upon mixing (Figure 6a-f) was utilized in programmed chemical/biochemical reactions. Separately immobilized reactants (substrate/lipase) in different gels come in the immediate proximity to each other owing to the disruption of self-assembled gel upon mixing and consequently facilitated the enzymatic reaction in a regulated manner. This dissolution of complementary gels was also employed in pro-drug activation (conversion of chloramphenicol from chloramphenicol succinate in presence of CV lipase) through programmed enzymatic reaction (Figure 6h). With the advancement of structural modification to develop LMWHs for multifarious applications, design of stimuli-responsive amphiphiles is also of high demand. Hydrogelators are finding notable importance as drug/protein delivery vehicle owing to its ability to release entrapped cargo in response to stimuli like pH, temperature, enzymes, oxidizing or reducing agents.10,62,67 For instance, the drug delivery sites are reported to be acidic in inflammatory tissues, phagolysosomes of antigen presenting cells and cancer cells. In such occasions, it will be beneficial to develop a hydrogel that disintegrates at acidic pH for selective delivery of the drugs.68 Shome et al. rationally designed L-tyrosine and L-phenylalanine based cationic amphiphilic hydrogelators (29a-d, Chart 2) with tuned head groups to develop pH-responsive hydrogels.69 The gelator having tyrosinate as head group (29d) exhibited better sensitivity toward external pH. At physiological pH (pH = 7.4), the release of encapsulated biomolecules (like vitamin B12 and cytochrome c) from the hydrogels was caused by diffusion. Interestingly, ~95% release (9-10 times in comparison to that observed at physiological pH) of entrapped vitamin B12 was noted by disrupting the gel structure of the amphiphile containing tyrosinate head group (29d) upon lowering the pH from 7.4 to 5.5/2.0. Also the

24


Page 24 of 63

Page 25 of 63 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

retained structural integrity as well as the activity of released biomolecule ascertained the potential of this pH-sensitive hydrogel as drug delivery vehicle. In recent years, diabetes mellitus is one of the most common chronic metabolic disorder in which the person suffers from high blood sugar level due to inadequate production of insulin.70 Consequently, external insulin is needed to maintain a proper glucose level in human blood stream. Hence, glucose-sensitive materials are finding enormous prominence in the advancement of the insulin regulatory systems for hyperglycemic treatments.70 With this motivation, Mandal et al. developed a pyrene based phenylboronic acid (PBA) appended amphiphilic hydrogelator (30a,b, Chart 2) for glucose-responsive insulin release.71 The gelator can immobilize aqueous buffer solutions of different pH(pH = 8-12) while the corresponding sodium salt of the gelator (boronic acid) was found to form hydrogel at pH = 7.4 having MGC of 5 mg/mL. During the designing of the gelator molecule, the diolresponsive PBA and the pyrene moiety were judiciously included in the amphiphile's structure for fluorimetric sensing of trace amount of glucose (0.1 mM) at physiological pH. This gel also has the characteristic feature to swell in presence of glucose owing to the formation of boronate-diol adduct that lacks self-assembling ability (Figure 7). This glucoseinduced swelling of hydrogel was utilized towards the controlled release of insulin entrapped within the gel matrix. Moreover, the thixotropic self-recovery property of insulin-loaded hydrogel enhanced its utility as injectable soft materials. Thus, the development of stimulisensitive low-molecular-weight hydrogel is establishing their future use in biomedicinal applications. In addition to the potential applications of self-aggregated structures in above mentioned area, diversified supramolecular 3D network of gels have emerged as templates for developing different nanostructures. In the recent past, the nanomaterials have received 25


Langmuir 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

much interest because of their distinct features and prospective applications ranging from nanotechnology to nano-biotechnology.72 Synthesis and stabilization of nanomaterials within hydrogel matrix is also a challenging task in particular shape regulated formation of nanoparticles. So, it is essential to tune the template in such a way that itself can also provide active sites for in situ development of nanoparticles. However, most of these methods require external reducing agents. In literature, amino acids such as tryptophan, tyrosine, and arginine are known to be used for the synthesis of gold nanoparticles (GNPs) by reduction of chloroaurate solution and also stabilize the GNPs.73 In this context, Mitra et al. have reported tryptophan-based cationic hydrogelators (31,32, Chart 3) with insertion of an additional amino acid residue (L-proline/L-phenylalanine) having varying 3D-fibrillar network, such as fibers, thin sheets, helical, lamellar, etc.74 These hydrogels of different 3D network are elegant host for in-situ shape-controlled (sheet/wire/octahedral/decahedral) synthesis of GNPs without the requirement of any external reducing/capping agent (Figure 8a-l). The nanohybrids of hydrogels and metal nanoparticles (MNPs) have imminent prospects towards the development of biomaterials, labelling agent, sensors and many others. Simultaneously, nanohybrids of organogel and MNPs have huge applications in supramolecular optoelectronic devices, and associated areas. However, synthesis of GNP and its stabilization in organogel is not an easy task mainly because of the unavailability of suitable gold ion precursor, which is soluble in organic medium. . Das and co-workers reported a pH-responsive transition of soft nanocomposite from in situ GNP-hydrogel to GNP-organogel.75 We synthesized redox active amino acid (L-tryptophan or methyl substituted L-tryptophan residue) based gelator molecules (22a,b, Chart 2) where the hydrophobic part was hooked up with long alkyl chain with the presence of free carboxylic acid residue at the polar end. At higher pH, salt of the amphiphiles are susceptible to form hydrogel and able to synthesize GNPs devoid of any reducing/capping agents (Figure 8m). Upon shifting the pH of the hydrogel to acidic, 26


Page 26 of 63

Page 27 of 63 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

carobxylates of amphiphiles get converted to the carboxylic acids, which formed gel in the organic medium with concurrent entrapment of the GNPs leading to the formation of GNPsorganogel nanohybrid without any alteration of size and shape of the nanoparticles (Figure 8n,o). These amphiphilic gelators efficiently transfer the metallic nanoparticles across the aqueous/organic domain simply by changing the pH of the medium. There is an increasing prevalence of biomedicinal prospect of soft-materials and one of the major arena is the treatment of microbial infections, especially those associated with wound healing and biomedical implants.51 Different strategies to develop materials having antimicrobial activity to prevent infections is on high demand. Langer and co-workers had reported the development of antifungal gel where amphotericin B was doped within dextranbased hydrogel (amphogel) that kills fungi within 2 h of contact against Candida albicans.76 Intrinsic bactericidal property would be more beneficial for wider applications of soft hydrogels. LMWGs having intrinsic anti-microbial activity would be highly advantageous to the increasing resistance of microbes against traditional drugs. To this end Debnath et al. have enlightened genesis of short peptide (e.g., L-isoleucine/phenylalanine) tethered cationic amphiphiles (33a-d, Chart 3) by tuning the hydrophobic unit like N-fluorenyl-9methoxycarbonyl (Fmoc) or long alkyl chain with the inclusion of a pyridinium group at the C-terminal.77 The structural modulation of amphiphiles facilitates to obtain different pattern of fibrillar network in the gel state owing to the change in the HLB. Importantly, these amphiphiles are very much efficient to show antibacterial/microbial activity (minimum inhibitory concentration (MIC) of 10 µg/mL) towards different microbes like Gram positive/negative bacteria and fungus. In another work, Mitra et al. reported the inherent growth-inhibiting

activity

of

dipeptide

(L-proline/phenylalanine/tryptophan)

based

quaternized cationic amphiphilic hydrogelators (31a,b) on several Gram-positive (MIC = 0.110 µg/mL) and Gram-negative bacteria (MIC = 5-150 µg/mL), as well as on fungus (MIC = 27


Langmuir 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

1-50 µg/mL).78 The bactericidal effect was influenced by the head-group structure particularly in case of Gram-negative bacteria and fungus. In order to broaden the spectrum of antibacterial properties, silver nanoparticle (AgNP) was synthesized in situ within the hydrogels as AgNP possesses prominent antimicrobial efficiency against both Gram-positive and Gram-negative bacteria.79 In situ synthesis of AgNP in the gel matrix is an elegant strategy as the soft-nanocomposites are prepared without the assistance of any exogenous materials like reducing/capping agents.80 In this regard, Dutta et al. developed L-tryptophan containing hydrogelating amphiphiles (25g) having different counterions varying from chloride to benzoate and acetate.81 These gel matrix are highly proficient for in situ synthesis of AgNPs under mild condition (Figure 9a,b). These nanocomposites exhibited excellent antibacterial activity against Gram-positive (MIC = 2-5 µg/mL) and Gram-negative (MIC = 20-100 µg/mL) bacteria (Figure 9c-f). Furthermore, Das and co-workers also designed cholesterol-based hydrogelators (34a-c, Chart 3) comprising amino acids hooked by an oxy-ethylene linker with different hydrophilic terminals.82 Hydrogelators with free NH2 group at the terminal were utilized for in situ synthesis of AgNPs that showed excellent bacteria killing ability. Importantly all these softnanocomposites exhibited substantial cytocompatibility (>80%) against mammalian cells. Inclusion of Carbon Nanomaterials within Gels: Tuning Viscoelastic Property. In spite of having versatile physicochemical properties and diverse applications across the scientific domain, major limitations of supramolecular gels are poor mechanical stiffness, instability and ready degradation under stress.83 Thus, besides the structural modification in the amphiphilic gelators, researchers are also putting effort to improve the mechanical stiffness of physical gels by the development of soft-nanocomposites with the inclusion of exogenous materials that will have fitting integration within the interstitial space of gel 28


Page 28 of 63

Page 29 of 63 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

network.84 Alongside metallic nanoparticles, carbonaceous nanomaterials like carbon nanotube (CNT), graphene oxide (GO) and/or reduced graphene oxide (RGO) are finding prominent importance owing to their nanoscale dimension and intrinsic mechanical strength. Integration of this nanomaterials within the intertwined fibrillar network of supramolecular gels is an intriguing way to prepare gel-nanocomposites where both components complement their properties.84 In the process of self-assembled gelation, the mobility of solvents get arrested due to the capillary forces of self-assembled fibrillar network (SAFIN). CNTs having dimension akin to the SAFIN can be used to reinforce the existing supramolecular network. At the same time, it would be more interesting if CNTs could participate in the formation of SAFIN. The feasibility of CNTs to assist in gelation is quite sensible if it can be dispersed in the immobilizing domain through debundling. Mandal et al. from our group reported the outstanding improvement of gelation efficiency (MGC 1.75 (% w/v) to 0.15 (% w/v)) of dipeptide (e.g., L-tryptophan/phenylalanine) based amphiphiles (22e) with C-16 alkyl residue at N-terminus and free carboxylic acid moiety at C-terminus after the addition of small amount (0.1 (% w/v)) of acid functionalized single walled CNTs (f-SWNTs or SWNTCOOH) and pristine SWNT.85 Addition of SWNTs to a free flowing solution of amino acid based weak gelator in organic or aqueous medium improved the gelation efficiency by many fold resulting in the formation of a super-efficient self-supporting gel. Surprisingly, minimum amount of SWNT facilitated the generation of SAFIN in the gelator solution whereas individually there were very few discrete fibers without any network (much lower than the MGC). The influence of molecular designing on the gelation efficiency in presence of SWNTs was further investigated by varying the amino acid residues in the dipeptide amphiphiles. Storage modulus (G') and loss modulus (G") are the two important parameters related to viscoelastic property of gels. G' defines to the ability of a deformed materials to restore its native form while G" delineates the flow behaviour of the material under stress. 29


Langmuir 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

For viscoelastic materials like gels G'> G" (G' and G" ~ ω0; ω =angular frequency) and in the sol state G" > G' (G'~ ω2 and G" ~ω). Incorporation of nanomaterials into the interstitial space within gel network is expected to improve mechanical rigidity with modified gelation ability. Mechanical rigidity (G') of the soft nanocomposite remarkably enhanced up to 25000 Pa (~6 fold higher than that of native gel) upon integration of CNTs within the hydrogel matrix. This became possible because of the complementary interactions between CNTs and the SAFIN of the hydrogel through the hydrophilic group and the long hydrocarbon chain hooked up with amino acid residues having extended aromatic rings in the gelating amphiphiles. In another instances, Mandal et al., has also developed a series of amino acid/dipeptide based amphiphilic hydrogelators (35a,b, Chart 3) comprise of a quaternary ammonium/imidazolium group as hydrophilic head and a C16 alkyl chain as the hydrophobic segment.86 These novel hydrogel matrix are very much efficient to integrate pristine-SWNT in their intertwined fibrillar network resulting in 85 fold increment in the mechanical stiffness (Figure 10a). Designing of both organogelator and hydrogelator from a common structural scaffold is a challenging task. Kar et al. used a simple protection-deprotection chemistry to achieve the conversion between organogel and hydrogel by synthesizing amino acid/peptide (Lalanine/phenylalanine/tryptophan) based amphiphilic precursors (36a-f, Chart 3). These compounds have a naphthyl group at the hydrophobic end and a primary amine-containing hydrophilic ethyleneoxy residue as polar unit.87 Protection at the primary amine of the amphiphiles by tert-butyloxycarbonyl (Boc) group yielded efficient organogelators (36a,c,e) while elimination of Boc group resulted in the amphiphiles, which are capable of immobilizing water (36b,d,f). So far we have discussed on the formation tailor-made selfassemblies leading the development of supramolecular hydrogels and organogels. There is another category of gelators, which simultaneously act as both LMHGs and LMOGs, are 30


Page 30 of 63

Page 31 of 63 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

referred as ambidextrous gelators (AGs). Although huge number of LMHGs and LMOGs have been discussed over the last decades, reports on AGs are very few. We have developed pyrene based amino acid tethered ambidextrous gelators with varying functionality from tertiary amine to imidazolium unit (37a-c, 38, Chart 3).88,89 Besides CNTs, another kind of CNMs might get included into the gel matrix like GO and/or rGO. Honeycomb like planar structure of these 2D-allotropes of carbon is the key factor for its inclusion within the π-π stacking of gel network.84 Amphiphiles (37a-c) having tertiary amine functionality, are efficient to integrate the CNT in the gel matrix with the enhancement of mechanical stiffness up to ~14000 Pa (CNT-organogel composite) and ~3900 Pa (CNT-hydrogel composite).88 In other instances, 2D GO/rGO incorporated hydrogel (38) having imidazolium unit showed significant improvement in G' (GO-hydrogel and rGO-hydrogel composites showed a G' value of approximately 26600 Pa and 22600 Pa, respectively) which was almost 7.5-fold and 6.5 fold higher than that of the G' of native hydrogel at MGC, respectively.89 Analogous trends in mechanical stiffness were observed for GO/rGO organogel composites. Complementary interaction between the π-electronic surface of 2D graphene sheet and the pyrene moieties of gelator is crucial for the incorporation of nanomaterials within the gel fibres (Figure 10b,c). These ambidextrous gels also exhibited intrinsic fluorescence property that could find immense importance in the area like organic light-emitting diodes, photovoltaic cells and sensors. Structure Specific CNM Inclusion into Gel Matrix. Inclusion of exogenous nanomaterials like CNTs, GO, metallic nanoparticles within the interstitial spaces of SAFINs aided beneficial changes in their properties. Nevertheless, incorporation of carbon nanomaterials (CNMs) in the fibrillar network is expected to depend on the dimensions of the CNMs and also on the structure of gelating amphiphile. To this end, 31


Langmuir 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Choudhury et al. reported the rational design of neutral hydrogelator (39a-c) without any charge (triethyleneglycol monomethyl ether residue), at the polar part which can efficiently immobilize plain water.90 The hydrophobic end was judicially modulated from C-16 long chain to the extended conjugated pyrenyl moiety to investigate the specific integration of CNM within the gels. Aggregation pattern of amphiphiles at the self-assembled state is mainly categorized by two types: H-aggregation (parallel face-to-face stacking to develop a sandwich-type array) and J-aggregation (head-to-tail arrangement to form stair-like array). C16 alkyl chain-based gelator (39a) disperses and includes 1D allotropes of carbon, SWNT within gel matrix (Figure 10d). Interestingly, the pyrene-containing gelator can incorporate both 1D and 2D allotropes of carbon (i.e., SWNTs and GO) within intertwined fibrillar network (Figure 10d). It may be inferred that long alkyl chain containing amphiphile possesses J-aggregation that facilitated the integration only 1D allotrope of carbon, while extended π-conjugated pyrene bearing neutral gelator having H-aggregation pattern suited well for inclusion of both 1D (SWNT) and 2D (GO) allotropes of carbon (Figure 10d). These soft nanohybrids could be employed in material science to biomedicine by selective inclusion of the CNMs of varying size and shape. Organic Nanoparticles. One of the recently emerged supramolecular manifestations of self-assemblies is organic nanoparticles, which is generally defined as solid particles made of organic compounds (mostly lipids or polymers) having diameter in the range of 10 nm to 1 µm. Investigations are on the rise for designing of fluorescent organic nanoparticles (FONPs) due to their high potential in wide range of applications from electronic to photonic, medicine to biotechnology, and so forth.91 Tuning the structural moiety of small molecules plays a vital role in the process of self-aggregation of π-conjugated oligomers towards the development of 32


Page 32 of 63

Page 33 of 63 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

spherical aggregates. Generally, most of the organic fluorophores have strong fluorescence in dilute solutions, but they exhibit poor emission upon aggregation and in the solid states due to aggregation-caused quenching (ACQ). Encouragingly, few organic nanoparticles derived from rotor like molecules such as tetraphenylethene, siloles, cyano-substituted diarylethene and distyrylanthracene derivatives were found to show aggregation induced emission (AIE) due to restricted intramolecular rotation (RIR) or planarization of the π-conjugated backbone.91 Hence, these smart self-assembled materials are very much useful in biosensing, bioimaging, drug delivery and other biomedicinal tasks.91 In this context, 1,4,5,8-naphthalenediimides (NDIs) have gained notable attention. Extensive efforts have been made to enhance the emission and modulate the self-aggregation pattern of the NDI derivatives through core substitution using amino groups or N-substitution with H-bonding groups or by tuning the linker moiety between the NDI core and the terminal motif.3,92 Recently, Choudhury et al. reported highly water dispersible green fluorescent organic nanoparticles of 30-90 nm derived from carboxybenzyl protected L-phenylalanine tethered NDI bola-amphiphile (40).93 This amphiphile showed weak blue fluorescence in molecularly dissolved DMSO solution. With the gradual increase in water content, the amphiphiles get self-assembled through H-aggregation to form spherical particles resulting strong green emission upon UV-light irradiation (Figure 11). This strong green emission of the bola-amphiphile in the presence of high water content (99% water in DMSO) is the result of AIE via excimer formation. The aromatic moieties and chiral bias in the molecular architecture facilitates the supramolecular organization through non-covalent interactions. These green FONPs, having good water dispersibility and cell viability, were efficiently exploited in cell imaging and drug delivery (Figure 11). Hence, NDI derivative-based FONPs could be set as a pillar in the biomedicinal arena along with other scientific disciplines.

33


Langmuir 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

CONCLUSIONS AND OUTLOOK In summary, this brief survey on different expressions of tailor-made self-assemblies by simple amphiphilic molecules along with their prospective diverse applications, make it very promising towards the development of functional soft-materials. The examples given in this feature article are important to provide an overview on synthesis of low-molecular-weight amphiphiles, variation of their structural moieties as well as their facile association to selfassembly. Moreover, this describes the structure-property relationships of self-assembled materials for diverse task specific applications. In spite of doing lot of research on self-assemblies, there are still many challenges hitherto for functional soft-materials to be employed for practical applications. Further development of new strategies involving the sequential and hierarchical self-organization of low-molecular-weight amphiphiles on a large scale is also needed. Hence, understanding the non-covalent interaction in the self-assemblies of small molecules will be very important. Progress in this regard may improve the outlook of the molecular self-organization and find the direction towards their novel applications in diversified fields of chemistry, physics, biology, materials science, nano-science and others. ACKNOWLEDGMENTS P.K.D. is thankful to Science and Engineering Research Board (SERB), Department of Science and Technology (DST), India for financial assistance (EMR/2017/000656). S. S. acknowledges DST, India and P.C & S. D. acknowledge Council Scientific and Industrial Research (CSIR), India for their research fellowship. REFERENCES 1. Lehn, J. "Supramolecular chemistry". Science 1993, 260, 1762-1763.

34


Page 34 of 63

Page 35 of 63 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

2. Lehn, J. M. Supramolecular Chemistry: Concepts and Perspectives. Wiley-VCH. 1995, ISBN 978-3-527-29311-7. 3. Zhang, X.; Chen, Z.; Würthner, F. Morphology control of fluorescent nanoaggregates by co-self-assembly of wedge- and dumbbell-shaped amphiphilic perylene bisimides J. Am. Chem. Soc. 2007, 129, 4886-4887 4. Israelachvili, J. N.; Thermodynamic and geometric aspects of amphiphile aggregation into micelles, vesicles and bilayers, and the interactions between them. Physics of Amphiphiles: Micelles, Vesicles and Microemulsions, 1985, 24-58. 5. Kunitake, T.; Okahata, Y.; Shimomura, M.; Yasunami, S.; Takarabe K.; Formation of stable bilayer assemblies in water from single-chain amphiphiles. Relationship between the amphiphile structure and the aggregate morphology. J. Am. Chem. Soc. 1981, 103, 73677368. 6. Fleming, S.; Ulijn, R.V. Design of nanostructures based on aromatic peptide amphiphiles, Chem. Soc. Rev. 2014, 43, 8150-8177. 7. Wolf, K. L.; Frahm, H.; Harms, H. The state of arrangement of molecules in liquids. Z Phys. Chem. Abt. B, 1937, 36, 237-287. 8. Menger, F. M. Remembrances of self-assemblies past. Langmuir 2011, 27, 5176-5183. 9. Estroff, L. A.; Hamilton, A. D.; Water gelation by small organic molecules. Chem. Rev., 2004, 104, 1201-1218. 10. Debnath, S.; Roy, S.; Ulijn, R.V. Peptide Nanofibers with Dynamic Instability through Non-Equilibrium Biocatalytic Assembly, J. Am. Chem. Soc. 2013, 135, 16789-16792. 11. Walde, P. Buidling artificial cells and protocell models: experiments approaches with lipid vesicles. BioEssays 2010, 32, 296-303. 12. Weiss, R. G., Terech, P. Molecular gels, materials with self-assembled fibrillar networks, Springer, New York, 2006. 35


Langmuir 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

13. Mao, Q.; Walde, P. Substrate effects on the enzymatic activity of α-chymotrypsin in reverse micelles. Biochem. Biophys. Res. Commun. 1991, 178, 1105-1112. 14. Melo, E. P.; Taipa, M. A.; Castellar, M. R.; Costa, S. M. B.; Cabral, J. M. S. Spectroscopic analysis of thermal stability of the Chromobacterium viscosum lipase. Biophys. Chem. 2000, 87, 111-120. 15. Langevin, D. Micelles and microemulsions. Annu. Rev. Phys. Chem. 1992, 43, 341-369. 16. Duynstee, E. F. J.; Grunwald, E. Organic reactions occurring in or on micelles. II. Kinetic and thermodynamic analysis of the alkaline fading of triphenylmethane dyes in the presence of detergent salts. J. Am. Chem. Soc. 1959, 81, 4542–4548. 17. Tascioglu, S. Micellar solutions as reaction media. Tetrahedron 1996, 52, 11113-11152. 18. Das, D.; Roy, S.; Das, P. K. Efficient and simple NaBH4 reduction of esters at cationic micellar surface. Org. Lett. 2004, 6, 4133-4136. 19. Dasgupta, A.; Mitra, R. N.; Roy, S.; Das, P. K. Asymmetric resolution in ester reduction by NaBH4 at the interface of aqueous aggregates of amino acid, peptide, and chiralcounterion-based cationic surfactants. Chem. Asian J. 2006, 1, 780-788. 20. Roy, S.; Das, D.; Dasgupta, A.; Mitra, R. N.; Das, P. K. Amino acid based cationic surfactants in aqueous solution: physicochemical study and application of supramolecular chirality in ketone reduction. Langmuir 2005, 21, 10398-10404. 21. Martinek, K.; Levashov, A. V.; Khmelnitsky, Y. L.; Klyachko, N. L.; Berezin, I. V. Colloidal solution of water in organic solvents: a microheterogeneous medium for enzymatic reactions. Science 1982, 218, 889-891. 22. Faeder, J.; Ladanyi, B. M. Molecular dynamics simulations of the interior of aqueous reverse micelle. J. Phys. Chem. B 2000, 104, 1033-1046. 23. Pileni, M. P. Nanosized particles made in colloidal assemblies. Langmuir 1997, 13, 32663276. 36


Page 36 of 63

Page 37 of 63 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

24. Carvalho, C. M. L.; Cabral, J. M. S. Reverse micelles as reaction media for lipases. Biochimie 2000, 82, 1063-1085. 25. Kawamoto, S.; Takasu, M.; Miyakawa, T.; Morikawa, R.; Oda, T.; Futaki, S.; Nagao, H. Inverted micelle formation of cell-penetrating peptide studied by coarse-grained simulation: importance of attractive force between cell-penetrating peptides and lipid head group. J. Chem. Phys. 2011, 134, 095103-095108. 26. Luisi, P. L.; Magid, L. J.; Fendler, J. H. Solubilization of enzymes and nucleic acids in hydrocarbon micellar solution. Crit. Rev. Biochem. Mol. Biol. 1986, 20, 409-474. 27. Creagh, A. L.; Prausnitz, J. M.; Blanch, H. W. Structural and catalytic properties of enzymes in reverse micelles. Enzyme Microb. Technol. 1993, 15, 383−392. 28. Fletcher, P. D. I.; Robinson, B. H.; Freedman, R. B.; Oldfield, C. Activity of Lipase in Water-in-oil Microemulsions. J. Chem. Soc. Faraday Trans. 1 1985, 81, 2667-2679 29. Das, P. K.; Chaudhuri, A. On the origin of unchanged lipase activity profile in cationic reverse micelles. Langmuir 2000, 16, 76-80. 30. Das, D.; Das, P. K. Improving the lipase activity profile in cationic water-in-oil microemulsions of hydroxylated surfactants. Langmuir 2003, 19, 9114-9119. 31. Das, D.; Roy, S.; Mitra, R. N.; Dasgupta, A.; Das, P. K. Head group size or hydrophilicity of surfactant: the major regulator of lipase activity in cationic w/o microemulsions. Chem. Eur. J. 2005, 11, 4881-4889. 32. Mitra, R. N.; Dasgupta, A.; Das, D.; Roy, S.; Debnath, S.; Das, P. K. Geometric constraints at the surfactant headgroup: effect on lipase activity in cationic reverse micelles. Langmuir 2005, 21, 12115-12123. 33. Maiti, S.; Das, D.; Shome, A.; Das, P. K. Influence of varying sized gold nanoparticles in improving the lipase activity within cationic reverse micelles. Chem. Eur. J. 2010, 16, 19411950. 37


Langmuir 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

34. Maiti, S.; Ghosh, M.; Das, P. K. Gold nanorod in reverse micelles: a fitting fusion to catapult lipase activity. Chem. Commun. 2011, 47, 9864-9866. 35. Ghosh, M.; Maiti, S.; Dutta, S.; Das, D.; Das, P. K. Covalently functionalized SWNT at reverse micellar interface: a strategy to improve lipase activity. Langmuir 2012, 28, 17151724. 36. Mandal, D.; Ghosh, M.; Maiti, S.; Das, K.; Das, P. K. Water-in-oil microemulsion doped with gold nanoparticle decoratedsingle walled carbon nanotube: scaffold for enhancing lipase activity. Colloids Surf. B 2014, 113, 442-449. 37. Sarkar, S. Das, K.; Das, P. K. Hydrophobically tailored carbon dots toward modulating microstructure of reverse micelle and amplification of lipase catalytic response. Langmuir 2016, 32, 3890-3900. 38. Das, D. Das, P. K. Superior activity of structurally deprived enzyme-carbon nanotube hybrids in cationic reverse micelles. Langmuir 2009, 25, 4421–4428. 39. Bangham, A. D.; Horne, R. W. Negative staining of phospholipids and their structural modification by surface-active agents as observed in the electron microscope. J. Mol. Biol. 1964, 8, 660-668. 40. Savsunenko, O.; Matondo, H.; Messant, S. F.; Perez, E.; Popov, A. F.; Rico-Lattes, I.; Lattes, A.; Karpichev, Y. Functionalized vesicles based on amphiphilic boronic acids: a system for recognizing biologically important polyols. Langmuir 2013, 29, 3207-3213. 41. Ghosh, R.; Dey, J. Vesicle formation by L‑cysteine-derived unconventional single-tailed amphiphiles in water: a fluorescence, microscopy, and calorimetric investigation. Langmuir 2014, 30, 13516-13524. 42. Palivan, C. G.; Goers, R.; Najer, A.; Zhang, X.; Cara, A.; Meier, W. Bioinspired polymer vesicles and membranes for biological and medical applications. Chem. Soc. Rev. 2016, 45, 377-411. 38


Page 38 of 63

Page 39 of 63 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

43. Shome, A.; Kar, T.; Das, P. K. Spontaneous formation of biocompatible vesicles in aqueous mixtures of amino acid-based cationic surfactants and SDS/SDBS. ChemPhysChem 2011, 12, 369-378. 44. Dinda, S.; Ghosh M.; Das, P. K. Spontaneous formation of a vesicular assembly by a trimesic acid based triple tailed amphiphile. Langmuir 2016, 32, 6701-6712. 45. Gabizon, A. A.; Liposome circulation time and tumor targeting: implications for cancer chemotherapy. Adv. Drug Deliv. Rev. 1995, 16, 285-294. 46. Gabizon, A.; Shmeeda, H.; Barenholz, Y. Pharmacokinetics of pegylated liposomal doxorubicin: review of animal and human studies. Clin. Pharmacokinet. 2003, 42, 419-436. 47. Tasis, D.; Tagmatarchis, N.; Bianco, A.; Prato, M. Chemistry of carbon nanotubes. Chem. Rev. 2006, 106, 1105-1136. 48. Casey A., Herzog, E.; Lyng, F. M.; Byrne, H. J.; Chambers, G.; Davoren, M. Single walled carbon nanotubes induce indirect cytotoxicity by medium depletion in A549 lung cells. Toxicol. Lett. 2008, 179, 78-84. 49. Dinda, S.; Mandal, D.; Sarkar S.; Das, P. K. Self-Assembled vesicle-carbon nanotube conjugate formation through a boronate-diol Covalent Linkage. Chem. Eur. J. 2017, 23, 15194-15202. 50. Mandal, D.; Dinda, S.; Choudhury, P.; Das, P. K. Solvent induced morphological evolution of cholesterol based glucose tailored amphiphiles: transformation from vesicles to nanoribbons. Langmuir, 2016, 32, 9780-9789 51. Zhang, Y.; Kuang, Yi; Gao, Y.; Xu, B. Versatile small-molecule motifs for self- ssembly in water and the formation of biofunctional supramolecular hydrogels. Langmuir 2011, 27, 529-537.

39


Langmuir 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

52. Ikeda, M.; Fukuda, K.; Tanida, T.; Yoshiia, T.; Hamachi, I. A supramolecular hydrogel containing boronic acid-appended receptor for fluorocolorimetric sensing of polyols with a paper platform. Chem. Commun. 2012, 48, 2716-2718. 53. Hirst, A. R.; Escuder, B.; Miravet, J. F.; Smith, D. K. High-tech applications of selfassembling supramolecular nanostructured gel-phase materials: from regenerative medicine to electronic devices. Angew. Chem. Int. Ed. 2008, 47, 8002-8018. 54. Steed, J. W. Supramolecular gel chemistry: developments over the last decade. Chem. Commun. 2011, 47, 1379-1383. 55. Hoeben, F. J. M.; Jonkheijm, P.; Meijer, E. W. Schenning, A. P. H. J. About supramolecular assemblies of π-conjugated systems. Chem. Rev. 2005, 105, 1491-1546. 56. Abdllah, D. J.; Weiss, R. G. Organogels and low molecular mass organic gelators. Adv. Mater. 2000, 12, 1237-1247. 57. Bhattacharya, S.; Ghosh, Y. K. First report of phase selective gelation of oil from oil/water mixtures. Possible implications toward containing oil spills. Chem. Commun. 2001, 185-186. 58. Kar, T.; Debnath, S.; Das, D.; Shome, A.; Das, P. K. Organogelation and hydrogelation of low-molecular-weight amphiphilic dipeptides: pH responsiveness in phase-selective gelation and dye removal. Langmuir 2009, 25, 8639-8648. 59. Debnath, S.; Shome, A.; Dutta, S.; Das, P. K. Dipeptide-based low-molecular-weight efficient organogelators and their application in water purification. Chem. Eur. J. 2008, 14, 6870-6881. 60. Suh, J. K. F.; Matthew, H. W. T. Application of chitosan-based polysaccharide biomaterials in cartilage tissue engineering: a review. Biomaterials 2000, 21, 2589-2598. 61. Lowik, D. W. P. M.; Leunissen, E. H. P.; van den Heuvel, M.; Hansen, M. B.; van Hest, J. C. M. Stimulus responsive peptide based materials. Chem. Soc. Rev. 2010, 39, 3394-3412. 40


Page 40 of 63

Page 41 of 63 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

62. van Bommel, K. J. C.; van der Pol, C.; Muizebelt, I.; Friggeri, A.; Heeres, A.; Meetsma, A.; Feringa, B. L.; van Esch, J. Responsive cyclohexane-based low-molecular-weight hydrogelators with modular architecture. Angew. Chem. Int. Ed. 2004, 43, 1663-1667. 63. Das, D.; Dasgupta, A.; Roy, S.; Mitra, R. N.; Debnath, S.; Das, P. K. Water gelation of an amino acid-based amphiphiles. Chem. Eur. J. 2006, 12, 5068-5074. 64. Roy, S.; Dasgupta, A.; Das, P. K. Alkyl chain length dependent hydrogelation of ltryptophan-based amphiphiles. Langmuir 2007, 23, 11769-11776. 65. Das, D.; Roy, S.; Debnath, S.; Das, P. K. Surfactant-stabilized small hydrogel particles in oil: hosts for remarkable activation of enzymes in organic solvents. Chem. Eur. J. 2010, 16, 4911-4922. 66. Mandal, D.; Choudhury, P.; Sarkar, D.; Das, P. K. Dissipation of self-assemblies by fusion of complementary gels: an elegant strategy for programmed enzymatic reactions. Chem. Commun. 2017, 53, 7844-7847. 67. Eelkema, R.; van Esch, J. H. Catalytic control over the formation of supramolecular materials. Org. Biomol. Chem. 2014, 12, 6292-6296. 68. Trevani, S.; Andonegui, G.; Giordano, M.; Lopez, D.; Gamberale, R.; Minucci, F.; Geffner, J. R. Extracellular acidification induces human neutrophil activation. J. Immunol. 1999, 162, 4849-4857. 69. Shome, A.; Debnath, S.; Das, P. K. Head group modulated pH responsive hydrogel of amino acid based amphiphiles: entrapment and release of Cytochrome c and Vitamin B12. Langmuir 2008, 24, 4280-4288. 70. Zaykov, A. N.; Mayer, J. P.; DiMarchi, R. D. Pursuit of a perfect insulin. Nat. Rev. Drug Discov. 2016, 15, 425-439.

41


Langmuir 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

71. Mandal, D.; Mandal, S. K.; Ghosh, M; Das, P. K. Phenylboronic acid appended pyrene based low molecular weight injectable hydrogel: glucose stimulated insulin release. Chem. Eur. J. 2015, 21, 12042-12052. 72. Daniel, M. C.; Astruc, D. Gold nanoparticles: assembly, supramolecular chemistry, quantum size related properties, and applications toward biology, catalysis, and nanotechnology. Chem. Rev. 2004, 104, 293-346. 73. Shao, Y.; Jin, Y.; Dong, S. Synthesis of gold nanoplates by aspartate reduction of gold chloride. Chem. Commun. 2004, 1104-1105. 74. Mitra, R. N.; Das, P. K. In situ preparation of gold nanoparticles of varying shape in molecular hydrogel of peptide amphiphiles. J. Phys. Chem. C 2008, 112, 8159-8166. 75. Kar, T.; Dutta, S.; Das, P. K. pH triggered conversion of soft nanocomposites: in situ synthesized AuNP hydrogel to AuNP organogel. Soft Matter 2010, 6, 4777-4787. 76. Zumbuhel, A. L.; Kuhn, F, D.; Astashkina, A.; Long, L.; Yeo, Y.; Iaconis, T.; Ghannoum, M.; Fink, G. R.; Langer, R.; Kohane, D. S. Antifungal hydrogels. Proc. Natl. Acad. Sci. U. S. A. 2007, 104, 12994-12998. 77. Debnath, S.; Shome, A.; Das, D.; Das, P. K. Hydrogelation through self-assembly of fmoc-peptide functionalized cationic amphiphiles: potent antibacterial agent. J. Phys. Chem. B 2010, 114, 4407-415. 78. Mitra, R. N.; Shome, A.; Paul, P.; Das, P. K. Antimicrobial activity, biocompatibility and hydrogelation ability of dipeptide-based amphiphiles. Org. Biomol. Chem. 2009, 7, 94-102. 79. Gurunathan, S.; Han, J. W.; Kwon, D. N.; Kim, J. H. Enhanced antibacterial and antibiofilm activities of silver nanoparticles against gram-negative and gram-positive bacteria. Nanoscale Res. Lett. 2014, 9, 373-389. 80. Tehfe, M. A.; Jamois, R.; Cousin, P.; Elkoun, S.; Robert, M. In situ synthesis and characterization of silver/polymer nanocomposites by thermal cationic polymerization 42


Page 42 of 63

Page 43 of 63 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

processes at room temperature: initiating systems based on organosilanes and starch nanocrystals. Langmuir 2015, 31, 4305-4313. 81. Dutta, S.; Shome, A.; Kar, T.; Das, P. K. Counterion-induced modulation in the antimicrobial activity and biocompatibility of amphiphilic hydrogelators: influence of in-situsynthesized Agnanoparticle on the bactericidal property. Langmuir 2011, 27, 5000-5008. 82. Dutta, S.; Kar, T.; Mandal, D.; Das, P. K. Structure and properties of cholesterol-based hydrogelators with varying hydrophilic terminals: biocompatibility and development of antibacterial soft nanocomposites. Langmuir 2013, 29, 316-327. 83. Raeburn, J.; Cardoso, A. Z.; Adams, D. J. The importance of the self-assembly process to control mechanical properties of low molecular weight hydrogels. Chem. Soc. Rev. 2013, 42, 5143-5156. 84. Bhattacharya, S.; Samanta, S. K. Soft-nanocomposites of nanoparticles and nanocarbons with supramolecular and polymer gels and their applications. Chem. Rev. 2016, 116, 1196712028. 85. Mandal, S. K.; Kar, T.; Das, D.; Das, P. K. The striking influence of SWNT–COOH on self assembled gelation. Chem. Commun. 2012, 48, 1814-1816. 86. Mandal, S. K.; Kar, T.; Das, P. K. Pristine carbon-nanotube-included supramolecular hydrogels with tunable viscoelastic properties. Chem. Eur. J. 2013, 19, 12486-12496. 87. Kar, T.; Mandal, S. K.; Das, P. K. Organogel–hydrogel transformation by simple removal or inclusion of N-Boc-protection. Chem. Eur. J. 2011, 17, 14952-14961. 88. Mandal, D.; Kar, T.; Das, P. K. Pyrene-based fluorescent ambidextrous gelators: scaffolds for mechanically robust SWNT-gel nanocomposites. Chem. Eur. J. 2014, 20, 1349-1358. 89. Mandal, S. K.; Mandal, D.; Das, P. K. Synthesis of a low-molecular-weight fluorescent ambidextrous gelator: development of graphene- and graphene-oxide-included gel nanocomposites. ChemPlusChem 2016, 81, 213-221. 43


Langmuir 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

90. Choudhury, P.; Mandal, D.; Brahmachari, S.; Das, P. K. Hydrophobic end-modulated amino-acid-based neutral hydrogelators: structure-specific inclusion of carbon nanomaterials. Chem. Eur. J. 2016, 22, 5160-5172. 91. Hong, Y.; Lama, J. W. Y.; Tang, B. Z. Aggregation-induced emission: phenomenon, mechanism and applications. Chem. Commun. 2009, 4332-4353. 92. Kobaisi, M. A.; Bhosale, S. V.; Latham, K.; Raynor, A. M.; Bhosale S. V. Functional naphthalene diimides: synthesis, properties, and applications. Chem. Rev. 2016, 116, 1168511796. 93. Choudhury, P.; Das, K.; Das, P. K. L‑Phenylalanine-tethered, naphthalene diimidebased, aggregation-induced, green-emitting organic nanoparticles. Langmuir 2017, 33, 45004510.

44


Page 44 of 63

Page 45 of 63 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

Table 1. Surface area per molecule (Amin) of aqueous micelles of amphiphile 6-18. (Reproduced with permission from Ref. [31]. Copyright [2005] [John Wiley and Sons], Reproduced from [Langmuir 2005, 21, 12115-12123]. Copyright [2005] American Chemical Society) Amphiphile

Amin (nm2)

Amphiphile

Amin (nm2)

6

1.18 ± 0.02

13

2.53 ± 0.03

7

1.42 ± 0.02

14

2.90 ± 0.05

8

2.30 ± 0.03

15

1.22 ± 0.01

9

1.23 ± 0.01

16

1.28 ± 0.02

10

1.40 ± 0.02

17

1.32 ± 0.01

11

2.20 ± 0.04

18

1.36 ± 0.03

12

2.12 ± 0.04

45


Langmuir 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Chart 1. Chemical structures of amphiphiles (1-18) used in micellar enzymology.

46


Page 46 of 63

Page 47 of 63 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

Chart 2. Chemical structures of amphiphiles (19-30) used in the formation of vesicle and supramolecular gel.

47


Langmuir 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Chart 3. Chemical structures of amphiphiles (31-40) used for the development of supramolecular gel and organic particles.

48


Page 48 of 63

Page 49 of 63 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

Scheme 1. Pictorial representation of different expression of supramolecular self-assemblies (micelle, reverse micelle, vesicle and gel fibres) originating from tailor-made amphiphiles.

49


Langmuir 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Scheme 2. Pictorial representation of different nano-materials (GNR, GNP, SWNT, SWNTGNP conjugate and CD) doped reverse micelle.

50


Page 50 of 63

Page 51 of 63 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

Figure 1. a) Reduction of esters with NaBH4 at aqueous cationic micellar surface, (Reproduced from [Org. Lett. 2004, 6, 4133-4136]. Copyright [2004] American Chemical Society) b) and c) Asymmetric reduction of pro-chiral ketones at aqueous cationic micellar surface of chiral surfactants, (Reproduced with permission from Ref. [19]. Copyright [2006] [John Wiley and Sons] and reproduced from [Langmuir 2005, 21, 10398-10404]. Copyright [2005] American Chemical Society, respectively).

51


Langmuir 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Figure 2. a) Lipase activity in cationic reverse micelles of hydroxylated surfactant. b) Effect of surfactant head-group size at the interface of reverse micelle in regulating lipase activity, (Reproduced with permission from Ref. [31]. Copyright [2005] [John Wiley and Sons]) c) Superior activity of hydrophobically adsorbed enzymes onto SWNTs upon incorporation in the reverse micelles of cationic surfactants. (Reproduced from [Langmuir 2009, 25, 44214428]. Copyright [2009] American Chemical Society).

52


Page 52 of 63

Page 53 of 63 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

Figure 3. a) Formation of monolayered vesicular self-assembly through H-aggregation from triple tailed amphiphile. Negatively stained TEM images of b) 19a, c) 19b and FESEM images of d) 19a, e) 19b, (Reproduced from [Langmuir 2016, 32, 6701-6712]. Copyright [2016] American Chemical Society) f) Formation of supramolecular vesicle-CNT conjugate through boronate-diol covalent linkage. g,h) Negatively stained TEM images of vesicle-CNT conjugate. i) percentage killing of B16F10 cells incubated with doxorubicin-loaded vesicle, CNT and vesicle-CNT conjugate for 12 h with varying doxorubicin concentration. Percent errors are within ± 5% in triplicate experiments, (Reproduced with permission from Ref. [49]. Copyright [2017] [John Wiley and Sons]).

53


Langmuir 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Figure 4. HRTEM images of (a) vesicle-21 in water (inset magnified image of bilayered vesicle) and self-assemblies of 21 in DMSO-water mixture (v/v = b) 1:4, c) 1:1, d) 4:1). e) Vesicle-to-Nanoribbon transformation from bilayered H-aggregated molecular packing to Jaggregated sheet like molecular arrangement, (Reproduced from [Langmuir, 2016, 32, 97809789]. Copyright [2016] American Chemical Society).

54


Page 54 of 63

Page 55 of 63 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

Figure 5. a) Photograph of phase selective gelation of 23c in toluene-water biphasic mixture. b) UV/Vis spectrum of aqueous solution of dye (crystal violet) indicating the time-dependent adsorption of the dye from water by xerogel of 23c. c) Photograph of crystal violet adsorption from water by xerogel of 23c, (Reproduced with permission from Ref. [59]. Copyright [2008] [John Wiley and Sons]).

55


Langmuir 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Figure 6. FESEM images of fibrillar network of a) gel-28, b) gel-21. c-f) FESEM images of time dependent destruction of fibrillar network the fused gels after 1h, 3h, 5h and 6h of incubation, respectively. g) Formation of boronate-diol adduct upon mixing of complementary gelator (28+21). h) Lipase-catalyzed hydrolysis of a pro-drug chloramphenicol succinate sodium salt to form an activated drug chloramphenicol entrapped within hydrogel of 28 and 21, respectively, (Reproduced with permission from Ref. [66]. Copyright [2017] [Royal Society of Chemistry]).

56


Page 56 of 63

Page 57 of 63 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

Figure 7. a) Glucose-responsive swelling behaviour of pyrene containing hydrogel (30b) assisted in vitro controlled release of entrapped insulin from the hydrogel matrix. FESEM images of compound 30b in the presence of different glucose concentration: b) 0, c) 6, d) 12, and e) 18 mM. f) Plot of the average gel fiber diameters at different glucose concentrations. g) Plot of the % degree of swelling with time at different glucose concentrations, (Reproduced with permission from Ref. [71]. Copyright [2015] [John Wiley and Sons]).

57


Langmuir 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Figure 8. a-l) TEM images of in situ synthesized gold nanoparticles (GNP) of varying shape in molecular hydrogel matrix derived from dipeptide based cationic amphiphiles (prolinetryptophan, tryptophan-proline, phenylalanine-tryptophan, tryptophan-phenylalanine, respectively), (Reproduced from [J. Phys. Chem. C 2008, 112, 8159-8166]. Copyright [2008] American Chemical Society) m) picture of in situ synthesized AuNP-hydrogel (22 analogues) composite n) pH responsive transfer of GNP from hydrogel to toluene layer and o) formation of AuNP-organogel nanocomposite after phase transfer. (Reproduced with permission from Ref. [75], Copyright [2010] [Royal Society of Chemistry]).

58


Page 58 of 63

Page 59 of 63 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

Figure 9. TEM images of a) AgNPs (negatively stained with uranyl acetate) synthesized using peptide based cationic amphiphile (25) having acetate as counter anion and b) nanocomposites prepared after centrifugation followed by lyophilization. FESEM images of E. coli (c) control and d) treated with 150 µg/mL AgNP-hydrogel (25 having acetate anion) and K. aerogenes (e) control and f) treated with 50 µg/mL AgNP- hydrogel (25 having acetate anion), (Reproduced from [Langmuir 2011, 27, 5000-5008]. Copyright [2011] American Chemical Society).

59


Langmuir 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Figure 10. TEM images of composite a) SWNT (0.1% w/v)-35b (0.7% w/v) (white arrows indicate the presence of gel fibers and the black arrows show the SWNT), (Reproduced with permission from Ref. [86]. Copyright [2013] [John Wiley and Sons]) b) dried hydrogel composite of 38 (0.5% w/v)-GO(0.1% w/v) and c) dried hydrogel composite of 38 (0.5% w/v)-rGO (0.1% w/v), (Reproduced with permission from Ref. [89]. Copyright [2016] [John Wiley and Sons]) d) Selective inclusion of SWNT and GO in neutral hydrogel-39a and 39c, respectively, (Reproduced with permission from Ref. [90]. Copyright [2016] [John Wiley and Sons]).

60


Page 60 of 63

Page 61 of 63 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

Figure 11. Formation of self-assembly induced green fluorescent organic nanoparticles of 40 in DMSO-water binary solvent mixture through H-type aggregation and bioimaging of the organic nanoparticles within B16F10 cells, (Reproduced from [Langmuir 2017, 33, 45004510]. Copyright [2017] American Chemical Society).

61


Langmuir 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

For Table of Content use only

Tailor-Made Self-Assemblies from Functionalized Amphiphiles: Diversity and Applications Saheli Sarkar, Soumik Dinda, Pritam Choudhury, and Prasanta Kumar Das* Department of Biological Chemistry, Indian Association for the Cultivation of Science Jadavpur, Kolkata – 700 032, India

62


Page 62 of 63

Page 63 of 63 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

AUTHORS INFORMATION Prasanta K Das received BSc (1992) and MSc (1994) in Chemistry from Jadavpur University, Kolkata. He completed PhD from CSIRIndian Institute of Chemical Technology, Hyderabad in 1999. After postdoctoral work at Massachusetts Institute of Technology, USA, he joined Department of Biological Chemistry, Indian Association for the Cultivation of Science, Kolkata in 2002. Presently he is a Senior Professor in the same department. His primary research domain is the design and development of novel supramolecular self-assemblies for exploiting them in diversified range from biocatalysis to biomedicine. He is a fellow of the Indian Academy of Sciences.

Saheli Sarkar earned her BSc (2011) and MSc (2013) in Chemistry from Jadavpur University, Kolkata, India. Subsequently, she joined the laboratory of Professor Prasanta Kumar Das at Indian Association for the Cultivation of Science, Kolkata to carry out her doctoral research. Her research work focuses on the development of carbon nanomaterial based soft nanocomposite for bioimaging and cellular transportation.

Pritam Choudhury received his BSc (2012) and MSc (2014) in Chemistry from Jadavpur University, Kolkata, India. Subsequently, he joined the laboratory of Professor Prasanta Kumar Das at Indian Association for the Cultivation of Science, Kolkata to pursuit his doctoral research. Currently he is working in the area of design and synthesis of self-assembled soft nanocomposites for antimicrobial & biochemical applications.

Soumik Dinda completed his BSc (2012) and MSc (2014) in Chemistry at the University of Calcutta, Kolkata and IIT Kharagpur, India, respectively. In the same year, he joined Indian Association for the Cultivation of Science, Kolkata to pursue his PhD work under the supervision of Professor Prasanta Kumar Das. Currently he is working in the area of synthesis and development of membrane mimetic supramolecular self-assemblies for biomedicinal applications.

63


Tailor-Made Self-Assemblies from Functionalized Amphiphiles

Recommend Documents