Determining Chiral Configuration of Diamines via Contact Angle

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Determining Chiral Configuration of Diamines via Contact Angle Measurements on Enantioselective Alanine-Appended Benzene-Tricarboxamide Gelators Sung Ho Jung, Ka Young Kim, Ahreum Ahn, Myong Yong Choi, Justyn Jaworski, and Jong Hwa Jung ACS Appl. Mater. Interfaces, Just Accepted Manuscript • DOI: 10.1021/acsami.6b02611 • Publication Date (Web): 17 May 2016 Downloaded from http://pubs.acs.org on May 24, 2016

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ACS Applied Materials & Interfaces

Determining Chiral Configuration of Diamines via Contact Angle Measurements on Enantioselective Alanine-Appended Benzene-Tricarboxamide Gelators Sung Ho Jung,† Ka Young Kim,† Ahreum Ahn,† Myong Yong Choi,*,† Justyn Jaworski,*,‡ and Jong Hwa Jung*,† †

Department of Chemistry, Gyeongsang National University, Jinju, 52828, Republic of Korea

‡

Chemical Engineering, Institute of Nano Science and Technology, Hanyang University, 222 Wangsimni-ro, Seoul 133-791, Republic of Korea * E-mail: [email protected]

KEYWORDS: Chiral Configuration, Enantiomer, Electrospun Film, Contact Angle, Enantioselectivity ABSTRACT: Spectroscopic techniques exist that may discern between enantiomers and assess chiral purity. A nonspectroscopic approach that may be directly observed could provide numerous benefits. Using chiral alanine-appended benzene-tricarboxamide gelators, we reveal a methanol gel system that is capable of providing visual discrimination between enantiomers of various diamines. Specifically, gelation is induced by supramolecular nanofiber assembly resulting from interaction between a chiral gelator and a diamine of opposing chirality (i.e., a heterochiral system). Upon further implementing the chiral gelator in electrospun fibers as solid state films, we revealed enantioselective surface wetting properties that allowed for determining chirality through contact angle measurements. While these two approaches of observable gelation and surface wetting offer non-spectroscopic approaches, we also find that the supramolecular nanofiber assembly was able to enhance the induced circular dichroism signal resulting from addition of chiral diamines allowing precise quantification of their enantiomeric purity.

■ INTRODUCTION Individual enantiomers of many common synthetic drugs can have drastically different pharmacological properties. For example, propranolol has been noted for treatment of heart disease or conversely as a contraceptive depending on its 1 chirality. Asymmetric synthesis, particularly for the case of pharmaceuticals, requires distinguishing of chiral molecules 2 and careful monitoring of enantiopurity. Because the growth in combinatorial asymmetric synthesis demands a high throughput means for detecting enantiomers, research in sensing molecular chirality continues to show exciting developments despite its inception many decades ago. More recent emphasis has turned to developing simple, rapid, and inexpensive stereoselective assays, as traditional approaches have been considered time consuming and require spectro3-5 scopic equipment. Nonetheless, significant work in recent years has also focused on advancing host systems for assessing chirality with greater enantiomeric discrimination, 6-13 14-21 22and hence reliability, via CD, NMR, and fluorescence 25 based techniques. To eliminate the need for spectroscopic equipment, several strategies have been implemented to allow direct visual detection of chirality of certain compounds of interest. For example, enantioselective collapse of supramolecular gels has

demonstrated controllable gel breakdown due to the pres26 ence of binap enantiomers and more broadly chiral amino 27 alcohols. Organic thin film transistors containing the appropriate polymeric components as the host receptor have also demonstrated chiral discrimination for specific com28 pounds. Recent reports have also provided a unique demonstration of using transient contact angle measurement for discerning chirality of liquid aliphatic diols placed on a 29-30 chiral polymer surface. In their demonstration, surface reorganization of the polymer, having chiral side chains, could create different wetting characteristics depending on the enantiomer within the liquid droplet. In the following work, we have provided a versatile system for chirality sensing by direct visual detection of gelation or contact angle and can also be used in conjunction with existing CD techniques (Figure 1). Specifically, we show for the first time the use of a supramolecular solid-state system able to discriminate enantiomeric amines through heterochiral or homochiral interface interactions. Our approach makes use of the formation of responsive methanol gels where the source of enantioselectivity is attributed to the preference of heterochiral interactions (i.e., opposite chirality of the gelator relative to diamine) resulting in gel formation rather than homochiral interactions (i.e., same chirality of the gelator

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Figure 1. Schematic representation showing the discrimination of enantiomeric amines by using the supramolecular solid-state system. and diamine). This effect, when implemented as a solid-state electrospun film, supports the chiral discrimination of diamines resulting in distinct contact angles depending on the configuration of the enantiomer. Direct visual detection of chirality is also achievable by observing any sol-gel transi31 tion (i.e., gelation) of the host and diamine guest mixture. Using the gelator host as the chiral auxiliary for fiber formation, the heterochiral discrimination of diamines can result in supramolecular assemblies to provide a strong ICD signal. By exhibiting a linear response curve to the percent enantiomeric excess of chiral mixtures of guest diamines, we reveal here that this enantioselective gelation technique is effective in assessing the chiral purity of diamines.

■ RESULTS AND DISCUSSION

Figure 2. Chemical structures of gelators 1D and 1L, the chiral diamines (2R, 2S, 3R, and 3S), the diamine (2RS), and the chiral monoamines (4R and 4S).

Individual enantiomers of many common synthetic drugs can have drastically different pharmacological properties. Initially, the formation of disc-shaped gelators was carried out by coupling L or D form alanine with benzene tricarbonyl chloride precursors as described in Scheme S1 in order to yield gelators 1D and 1L (Figure 2). While benzene tricarboxamide derivatives have been used previously for the supramolecular self-assembly of hydrogels,32 upon first examination of our gelator 1D, possessing D-form alanine moieties, and gelator 1L, having Lform alanine, we found these components to be incapable

of hydrogel formation. However, by mixing 1D or 1L with chiral diamines 2R or 2S in the appropriate solvent and subsequently heating the solution, we found that certain conditions allowed the formation of a thermoreversibleorganogels after several minutes of cooling and in some case the formation of a solid crystal (Figure S1 and Table S1). For instance, when gelator 1D (2.0 mM) was dissolved in methanol and mixed with 2S (0.5~3.0 equiv.), the heated solution was found to form a gel within several minutes of cooling if greater than 1 equiv. of 2S was used (Figure S2A). In contrast, 1D (2.0 mM) when dissolved in methanol and added to a solution of 2R (0.5~3.0 equiv.) did not result in gelation but rather precipitation (Figure S2B). This ability of 2S rather than 2R to initiate gelation of 1D was confirmed across various concentrations of gelator 1D (0.1-1 wt%) in methanol (Figure S3). Interestingly, the gelation occurred for only heterochiral mixed systems (i.e., 1D+2S or 1L+2R) while precipitation occurred in homochiral mixed systems (i.e., 1D+2R or 1L+2S). The D-form stereoisomer of alanine is the same right-handed configuration as the R-form chiral amines of 2R, such that D-form alanine selectively discriminates the R-form amines by homochiral recognition. In contrast, gelator 1D can effectively form a gel in methanol with 2S by favourable heterochiral interactions attributed to distinct intermolecular hydrogen-bonding interactions between 1D and 2S. Interestingly, no gelation occurred when 1D or 1L were added to a racemic mixture containing 0.75 equiv. of 2R and 0.75 equiv. of 2S (Figure S4) suggesting that 1 equiv. of diamine of opposite chirality relative to the gelator is necessary for gel stabilization. The compound (1R,2S)-1,2-diphenylethane-1,2-diamine, referred to as 2RS, (Figure S5A), which provides amines with both chiral configurations within a single molecule, did not cause gelation when added at 1.5 equiv. to the 1D or 1L. Furthermore, we also observed the gel formation of 1D and 1L upon addition of cyclohexane diamines such as 3R and 3S (Figure S6); however, methanol gels could not form for 1D or 1L in the presence of monoamines, such as 4R and 4S (Figure S7). This suggests that two amines may be needed to act as a bridge between neighboring gelators through electrostaic interactions.


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ACS Applied Materials & Interfaces find that 1D or 1L when mixed with the (2RS)-type did not exhibit any ICD peaks at 282 nm (Figure S5B), which indicates that any intermolecular interactions between 1D or 1L and 2RS were not sufficient to stabilize assembly for gel formation (Figure S5A). Furthermore, no linear dichroism (LD) spectrum of methanol gel 1D+2S was observed. The morphology of this organized structure found within the methanol gel can be seen in Figure 4A for gelator 1D and Figure S11A for gelator 1L. From the scanning electron microscopy (SEM) images of 1D+2S and 1L+2R, one can see the assembled nanofibers that had formed in the heterochiral systems which bundled into a network like structure to provide the stable gel. Here, the twisted nanofiber structures appear with a diameter in the range of 40-50 nm and several micrometers in length. In contrast, the precipitates formed from homochiral systems (1L+2S and 1D+2R) showed cubic structures with edge lengths on the order of 1-2 μm.

Figure 3. (A) CD spectra of methanol gels 1D and 1L (2.0 mM) with chiral diamines (2S and 2R, 1.5 equiv.). (B) UV-Vis spectra of methanol (a) gel and (b) sol.

In order to complement this visual assessment of heterochiral directed formation of methanol gels, we also measured the circular dichroism (CD) and absorption spectra of 1D and 1L mixed with various concentrations of chiral amines (2R and 2S) (Figures 3 and S8). The CD spectra of methanol gels prepared from 1D (2.0 mM) and 2S (1.5 equiv.) revealed a positive signal peak at 282 nm whereas the CD spectra of methanol gels prepared from 1L (2.0 mM) and 2R (1.5 equiv.) exhibited a strong negative signal centered at 282 nm (Figure 3A). The absorption band of the methanol gel appeared at around 270 nm (Figure 3B) in the region of the n-π* transition by electrostatic interaction between the gelator and the corresponding diamine of opposite chirality giving rise to induced circular dichroism (ICD). Self-assembly of gel fibers was thereby facilitated through electrostatic interactions between the gelator and the diamine as well as through aromatic stacking among adjacent gelators. In contrast, the CD spectra from 2.0 mM of gelators 1D or 1L prepared with only 0.5 equiv. of the diamine 2S or 2R, respectively was insufficient for gelation revealing no ICD but rather only the CD signals from the individual gelators and diamines (Figures S9 and S10A). Hence, the ICD could only be observed for heterochiral interactions (i.e., the opposing chirality of the gelator relative to the diamine) when 1 equiv. or greater of chiral diamine for the mixtures 1D+2S or 1L+2R. The CD spectra of 1D with mixtures of 2S exhibited ICD signals at 282 nm where it showed a direct correlation in signal strength with respect to the % enantiomeric excess (%ee) of 2S. Moreover, the signal intensity could be enhanced quantitatively by further addition of the diamine (Figure S10B) to initiate assembly through ππ stacking stabilized by electrostatic interactions. We also

Figure 4. SEM images of (A) methanol gels 1D with 2S and (B) precipitate 1D with 2R in methanol.

To identify how the distinct morphologies observed for the hetero- and homochiral systems could arise from stabilization of different gelator complex conformations with the corresponding diamines, we used several spectroscopic techniques. In the specific case of gelator 1D mixed with 2S, evidence of salt bridging was confirmed in the methanol gel by Fourier transform infrared (FT-IR) spectroscopy (Figure S12). The carboxylic acid of 1D without 2S appeared at 1736 cm-1; however, after addition of 2S, the twisted nanofiber formed and showed a decrease in this band. In addition, an asymmetric carboxylate stretching band33 was observed at 1545 cm-1 for the nanofiber gel prepared with 2S, suggestive of interaction between the carboxylate and/or amide groups of gelator 1D and the amine of 2S. We also observed the powder-XRD patterns of both the methanol gel formed in the heterochiral system 1L+2R as well as for the precipitate resulting from mixing the homochiral system of 1L+2S (Figure S13). For the homochiral system, the Bragg reflection pattern exhibited a broad peak centered at a 2θ value of 19.77 which could indicate a distance of 4.5 Å between the aromatic groups of 1L. In addition, the precipitate showed a peak centered at 2θ=6.94 for a lateral spacing of 1.27 nm which by comparison increased to 1.71 nm (2θ=5.17) in the methanol gel for the side-to-side gelator spacing which may be attributed to lateral positioning of the interacting 2R components between neighboring gelators.



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In order to consider this in relation to a possible structure model, the B3LYP/6-31+G(d) optimized molecular geometries of the monomer 1L were used as the building block for the dimer in complex with the chiral diamines (2R and 2S). The 1L dimer was found to be stabilized by N-H∙∙∙O=C hydrogen bonds (1.61 Å) which link the monomers to secure the dimer and lead to the formation of a strong stacking structure. In addition to the N-H∙∙∙O=C hydrogen bonds, a slightly dislocated aromatic π∙∙∙π stacking (4.31 Å) and weak C-H∙∙∙O=C interactions (1.97 Å) exhibited a key role in assembling a two-dimensional hydrogen bonded network for the dimer structure. In addition to steric effect of the carbonyl group in the monomer, it is also anticipated that the weak (aromatic) C55-H83 ∙∙∙O64=C62 interaction (2.27 Å) in the monomer units may collectively stabilize the aromatic rings in a face to face manner with each other, resulting in an orientation of slightly dislocated central aromatic rings in the assembling process.

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intermolecular proton transfers between the carboxyl and amine groups of 1L+2S (O13=C11-O14∙∙∙H129-N71 and O43=C41-O44∙∙∙H125-N69), while only one occurred for 1L+2R (O13=C11-O14∙∙∙H128-N111) (Figure S14). Additional calculations of 1L with the other chiral diamines, 3R and 3S, demonstrated a similar result as 2R and 2S showing one intermolecular proton transfer between the carboxyl and amine groups for 1L+3S (O13=C11-O14∙∙∙H121-N109), but none for 1L+3R (see Figure S15). The detailed values for the bond lengths, bond angles, and relative energies between 1L+2R and 1L+2S as well as 1L+3R and 1L+3S are provided in Table S2 and Table S3, respectively. As listed in Table S2, 1L+2S is more stable than 1L+2R, by 10.09 kcal/mol, which is in excellent agreement with the experimental observations. These findings support that a precipitate obtained from a mixture of 1L and 2S was more stable than that of the gel obtained by mixing 1L and 2R. From the predicted geometries, the distance between aromatic π∙∙∙π stacking become smaller for 1L+2R (4.27 Å) as compared to the 1L dimer alone (4.31 Å) for the dimer. Spectroscopic analysis of the methanol gels was conducted to improve our understanding of the induced circular dichroism signal observed for gelators exposed to diamines having opposing chirality (i.e., heterochiral relative to the gelator). The CD spectra of gelator 1D in methanol was examined with 1.5 equiv. (Figure S16) and 3 equiv. (Figure S17) of various ratios of mixed diamine 2R+2S or 3R+3S (Figure S18). The CD spectra of 1D with mixtures of 2R and 2S exhibited ICD signals at 282 nm where it showed a direct correlation in signal strength with respect to the % enantiomeric excess (%ee) of 2S. Similarly, the %ee of 3S could be assessed. The onset of gel formation for 1D occurred near 1 equiv. of 2S or 3S with increasingly stable gels formed at higher proportions of enantiomeric excess for the S-configured diamines. Therefore, we could see that the ICD signal enhancement followed the gelation ability in the mixed systems.

Figure 5. DFT calculated structures showing optimized complexes of 1L+2S and 1L+2R.

In looking at a dimer of 1L in complex with a single diamine, either 1L+2R or 1L+2S, the fully optimized structures of the complexes with 2R or 2S were obtained from one of the three possible binding sites with the 1L dimer (Figure 5). The six carboxylic acid groups present on the 1L dimer are seen to interact with both amines present on a single diamine of 2R suggesting a possible 2:3 complex of 1L+2R. In detail, the chiral diamines, 2R and 2S, were stabilized by hydrogen bonding between N-H or C-N groups of diamines and the C=O or O-H groups from each monomer unit in the ligand dimer, i.e., NH124∙∙∙O50=C (1.81 Å) and N-H129∙∙∙O14=C (1.68 Å) for 1L+2S; N-H127∙∙∙O70=C (1.80 Å) and C-N109∙∙∙H124-O (1.53 Å) for 1L+2R (Figure S14). Furthermore, the weak interactions between the C-H aromatic group of diamines and the C=O group of the dimer also stabilize the complexation of 1L+2R and 1L+2S. However, a more favourable hydrogen bonding geometry was calculated for 1L+2S than 1L+2R, as 1L and the chiral diamines produced two

In further exploring the application of this system for enantioselective discrimination of chiral diamines, we produced solid-state films of the nanofibers by electrospinning 1D or 1L (1.0 wt%) with poly(methyl methacrylate) (PMMA) (10.0 wt%) dissolved in DMSO solution. The films appeared as a fiber structure with a length of over several microns and a diameter on the order of 200 nm (Figure S19). As shown in Figure 6, to investigate if the films possessed any enantioselective surface wetting properties, contact angle measurements were performed using solutions of 2S, 2R, 3S, and 3R as test liquids. We find there is a transient decrease in each of the contact angles of 2S, 2R, 3S, and 3R droplets on the 1D:PMMA fibers. The contact angle values for the heterochiral 2S or 3S droplets on the films were 96o and 126o after 10 minutes, respectively, but interestingly their contact angles did not change as significantly over time as compared to the homochiral 2R or 3R droplets. The stability of larger contact angles in the heterochiral system are expected to arise from weak electrostatic interaction between 1D and the


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2S or 3S diamine components. In the case of the exponentially decreasing contact angles observed for the homochiral system of 1D with 2R or 3R, (eventually reaching values of 17o and 48o, respectively after 10 min), the smaller contact angle values may be attributed to stronger interactions between the amine groups of 2R or 3R and the carboxylate group of 1D at the homochiral fiber-liquid interface. It is important to note that similar chiral discrimination by contact angle observation was demonstrated for electrospun films prepared from 1L:PMMA (Figure S20). In the case of 1L:PMMA films, droplets of 2R or 3R showed large stable contact angles (heterochiral system) as compared to exponentially decaying small contact angles for droplets of 2S or 3S (homochiral system). Furthermore, we observed the contact angles of various concentrations of 2S and 2R on the electrospun films prepared from 1L:PMMA or 1D:PMMA. As shown in Figure S21, contact angles between 23o to 28o were observed for droplets of 2R placed on electrospun film prepared from 1D:PMMA. In contrast, the 2S droplets on the 1D:PMMA film exhibited large contact angles between 82o to 103o. Analogously, 1L:PMMA electrospun films revealed large contact angles for droplets of various concentrations of 2R (between 71o to 95o as seen in Figure S22) whereas droplets of various concentration of 2S each produced contact angles between 13 o to 31 o on the 1L:PMMA film.

1L:PMMA films to serve as a non-spectroscopic means of detecting chirality by providing opposing surface wetting properties to liquids of chiral diamines (i.e., heterochiral interfaces will provide larger, more stable contact angles). As far as one can tell from the literature, our results demonstrate a unique example of a supramolecular solidstate system capable of chiral amine discrimination through heterochiral or homochiral interface interactions. Extensive works on supramolecular assemblies arising from heterochiral or homochiral systems has shown other interesting properties including solvent-dependent selfdiscrimination34 and the ability to control the length of homochiral supramolecular fiber assemblies by addition of heterochiral capping components.35 Other systems have shown homochiral aggregation into nanofibers and disordered heterochiral precipitation yielding completely different morphologies.36 Heterochiral interactions between enantiomers in such cases have even shown to inhibit gelation,37 which is in contrast to our system. This is often seen to be the case even in helical polymeric systems;38,39 however, other rare examples of heterochiral mixtures resulting in gelation, such as the work described here, or also mesophase stabilization have been reported.40-42

■ CONCLUSION

Figure 6. A) Photograph showing the 2S, 3S, 2R, and 3R droplets on the 1D:PMMA electrospun films after 10 minutes. B) Time dependence of the contact angles of 2S, 3S, 2R, and 3R droplets on the 1D:PMMA film surface.

From control experiments using electrospun nanofibers without 1L or 1D, the contact angles for 2S and 3S after 10 minutes were 148o and 150o, respectively (Figure S23), thereby indicating the enantioselective role of the gelators in discriminating the enantiomer configuration of amines. From these results, we find the 1D:PMMA or

In conclusion, we have demonstrated a supramolecular gelator system capable of discerning the chirality of amines by virtue of its assembly into twisted nanofibers in the presence of a proper amine having opposing chirality. This assembled gel structure yielded an induced circular dichroism signal with a linear increase in CD intensity with increasing concentration of diamine which was used to quantify the chirality and enantiomeric purity of various diamine samples. As diamines are often utilized as building blocks of asymmetric synthesis,43 it is important to have a versatile means of detecting their chirality. In addition to proving that the gelator could be used to resolve chiral information by CD, we also found our system to be versatile enough for use by non-spectroscopic techniques. The enantioselectivity could be visually detected by observable gelation due to heterochiral interaction. In addition, electrospinning of the gelators into a solid-state fiber film allowed enantioselective discrimination of diamine liquids by contact angle measurements. The source of chiral discrimination was found to arise from distinct intermolecular interactions at the heterochiral interface (i.e., the solid gelator fiber film and liquid amine having opposing chirality) as compared to homochiral interfaces resulting in different surface wetting properties. We expect the versatility of our gelator-based chiral detection scheme may be valuable for discriminating amines as demonstrate here but perhaps also for future development and screening of other solid-state fiber films with alternative specificities.



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■ MATERIALS AND METHOD 1

13

Characterization. H and C nuclear magnetic resonance (NMR) spectroscopy were performed with a Bruker DRX 300 and 500 apparatus. A Shimadzu FT-IR 8400S instrument was used to obtain the infrared (IR) spectra using KBr pellets, across a range of 400 – 4000 cm-1. The mass spectra were measured on a JEOL JMS-700. Microscopy Studies. Scanning electron microscopy (SEM) images were obtained using a field emission scanning electron microscope (FE-SEM), Philips XL30 S FEG with an emission current of 10 μA and acceleration voltage of 5 to 15 kV. Circular Dichroism Studies. The circular dichroism (CD) spectra were determined using a Jasco J-815 CD spectrophotometer with a quartz cell (0.1 mm path length) across the range of 230 nm to 500 nm. The scans were taken at a sampling interval of 1.0 nm and response time of 1s with a rate of 50 nm/min. The scans were obtained at room temperature for the samples in methanol and water. We also obtained the CD spectra of 1D and 1L (2.0 mM) in the presence of amines (2R, 2S, 3R, and 3S, 0.5-3.0 equiv.). Preparation of Electrospun Films. Homogeneous solutions were employed for electrospinning and were prepared by dissolving PMMA (Mw: 350,000 g mol-1) with gelators (1D or 1L) in DMF for 24 hours under stirring conditions at room temperature using a 1.0 wt% concentration of gelators (1D or 1L) and 10.0 wt% of PMMA with respect to the gelators. Next, the homogeneous gelator and PMMA solution was loaded into a 10 mL plastic syringe housed with a metal needle (size 23 GA). The syringe was fixed horizontally within a syringe pump (KDS 200, KD Scientific, USA), and after the electrode of a high voltage power supply (Nano NC, Korea) was connected to the metal needle tip, the working distance between the needle tip and the ground electrode was set to 15 cm. The solution flow rate was then set to 20 μL/min and at the same time the electrospinning voltage was set to 17 kV. In these experiments, the temperature and relative humidity were maintained at 25 °C and 50 %, respectively. Contact Angle Measurements. The contact angles were measured using a contact angle goniometer (SmartDrop_Lab HS, FEMTOFAB Co., Ltd., Korea). A droplet of the amines (2R, 2S, 3R, and 3S) in water (1.0 mM) having volumes of 10.0 μL, were put onto a film prepared from electrospun 1D or 1L. The contact angle was determined on the basis of a contour curve-fitting method using the software (FEMTOFAB Co., Ltd., Korea) supplied by the vendor. In these experiments, the reversibility of the contact angles was examined by repeating the contact angle measurements for the same film. Preparation of Methanol Gels. A solution of 100 μL of amine (2R, 2S, 3R, and 3S, 0.5-3.0 equiv.) in methanol was added into a vial containing 500 μL of a solution of 1D or 1L [0.1 wt % in methanol]. Each mixture was heated to 40–

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50 °C and bath sonicated for three minutes in order to obtain a homogenous solution. This homogeneous solution was then allowed to cool gradually to ambient temperature to give the methanol gel. Computational Studies. Quantum chemical calculations based on density functional theory (DFT) were performed using the Gaussian 09 program.44 The full geometric optimization of 1L, a dimer of 1L, and its complexes with the chiral diamines were calculated by employing Becke’s three-parameter hybrid functions with the nonlocal correlation of Lee-Yang-Parr (B3LYP) method in the absence of symmetry constraints. The 6-31+G(d,p) basis set was used to predict the molecular structures and relative energies with zero-point energy corrections. Frequency calculations were also used to check the structures at the local energy minimum, wherein no imaginary frequencies were obtained to give a true minimum on the potential energy surface. The optimized geometries are listed in Table S2 and Table S3 wherein the structures were obtained using the Gaussview program. Synthesis Details of Compounds 1D and 1L. Trimesoyltri (D-alanine) (1D) and trimesoyltri(L-alanine) (1L) were prepared according to a literature procedure.45 A water solution (30 mL) of D-alanine or L-alanine (5.400 g, 0.02 mol) and NaOH (2.400 g, 0.06 mol) was also prepared. The freshly prepared 1,3,5-benzenetricarbonyl trichloride and alanine solution were alternatively added slowly in small portions into a round-bottomed flask in an ice-bath, together with the addition of a 4 mol L-1 NaOH solution to adjust the pH value to 8.0–9.0. This procedure was finished in an hour. The resulting solution was stirred for another 3 h then acidified by the addition of a concentrated HCl solution to adjust the pH value at 1–2. Further cooling of the resulting mixture in an icebath for several minutes gave a white precipitate, which was separated by filtration and washed by cold water. The crude product was recrystallized from hot water solution, giving a pure product in a yield of 80% after filtration and dryness. m.p.: 216–218 °C; 1H-NMR (300MHz, D2O) 8.13 (s, 3H, Ar–H), 4.45 (q, 3H, J = 7.2 Hz, –CH(CH3)COO), 1.39 (d, 9H, J = 7.2 Hz, –CH3); 13C NMR (125 MHz, D2O) 176.4, 167.9, 133.8, 129.4, 49.4, 15.9. IR (KBr, cm-1): 3366, 3220, 3015, 1727, 1623, 1589, 1535, 1460, 1335, 1309, 1212, 1169, 1118, 912, 807; ESI-MS: m/z 422.00 [M+]; Calculated for C18H21N3O9 [M+] 423.1278, Found 423.1254. ■ ASSOCIATED CONTENT Spectroscopic analysis is contained in Supporting Information. The Supporting Information is available free of charge on the ACS Publications website at http://pubs.acs.org.

■ AUTHOR INFORMATION Corresponding Author * E-mail: [email protected]


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ACS Applied Materials & Interfaces 12

Notes

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The authors declare no competing financial interest.

■ ACKNOWLEDGMENT This work was supported by the NRF (2015R1A2A2A05001400 and 2012R1A4A1027750) from the Ministry of Education, Science and Technology, Korea. In addition, this work was partially supported by a grant from the Next-Generation BioGreen 21 Program (SSAC, grant#: PJ011177022015), Rural development Administration, Korea. The main calculations carried out by the Supercomputing Center/Korea Institute of Science and Technology Information with supercomputing resources including technical support: (KSC-2015-C1-022)

■ ABBREVIATIONS

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14 15

16

PMMA; poly(methyl methacrylate)

■ REFERENCES 1

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Table of Contents


Determining Chiral Configuration of Diamines via Contact Angle

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