Subscriber access provided by UNIV OF LOUISIANA
Applications of Polymer, Composite, and Coating Materials
Fluorescent Probes for Sugar Detection Danielle Bruen, Colm Delaney, Dermot Diamond, and Larisa Florea ACS Appl. Mater. Interfaces, Just Accepted Manuscript • DOI: 10.1021/acsami.8b13365 • Publication Date (Web): 10 Oct 2018 Downloaded from http://pubs.acs.org on October 13, 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 36 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
ACS Applied Materials & Interfaces
Fluorescent Probes for Sugar Detection Danielle Bruen, Colm Delaney* , Dermot Diamond and Larisa Florea †
‡
Insight Centre for Data Analytics, National Centre for Sensor Research, School of Chemical Sciences, Dublin City University, Dublin 9, Ireland
†
Current address: School of Chemistry, University College Dublin, Science Centre - South
Belfield Dublin 4, Ireland ‡
Current address: AMBER and School of Chemistry, Trinity College Dublin, College Green,
Dublin 2, Ireland E-mail:
[email protected] Keywords: Boronic Acid, Fluorescence, Hydrogels, Glucose, Indirect Sensing, Pyranine
Abstract Herein a new class of polymerisable, boronic acid monomers are presented, which are used to generate soft hydrogels capable of accurate determination of saccharide concentration. Through exploitation of the interaction of these cationic boronic acid with an anionic fluorophore, 8hydroxypyrene-1,3,6-trisulfonic acid trisodium salt (pyranine), a two-component sugar-sensing system was realised. In the presence of such cationic BAs (o-BA, m-BA and p-BA), the fluorescence of pyranine becomes quenched, due to the formation of a non-fluorescent boronic acid-fluorophore complex. Upon addition of saccharides, formation of a cyclic boronate ester
ACS Paragon Plus Environment
1
ACS Applied Materials & Interfaces 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 2 of 36
results in dissociation of the non-fluorescent complex and recovery of the pyranine fluorescence. The response of this system was examined in solution with common monosaccharides, such as glucose, fructose and galactose. Subsequent polymerisation of the boronic acid monomers yielded cross-linked hydrogels, which showed similar reversible recovery of fluorescence in the presence of glucose.
Introduction Boronic acids (BAs) have been investigated for many potential applications, such as purification of glycoproteins by affinity chromatography, protecting groups in carbohydrate chemistry and as 1
2
coupling reagents in the formation of new C-C bonds. This versatility originates from their trigonal 3
planar geometry and vacant orthogonal p-orbital, which consequently renders them Lewis acidic.
3
This Lewis acidity also enables BA groups to form strong and reversible interactions with saccharides, anions, neurotransmitters such as dopamine and a-amino acids. Arylboronic acids 4
5
3
typically have a pK around 8, which can be reduced by 2-3 units when bound to saccharides, due a
6
to the electron-withdrawing capability of the sugar molecule. As a result, BAs are suitable for 7
saccharide sensing within the pH range of physiological fluids. Synthesis of BA-substituted 8
fluorophores for the detection of glucose has significant clinical potential, in particular for the detection, diagnosis and monitoring of diseases, such as diabetes.
9-15
To date, most BA-based fluorescent sensors have focused on exploiting well-characterised quenching mechanisms associated with discrete molecules. Appropriate covalent attachment of a BA moiety to a fluorophore exhibiting internal charge transfer (ICT) or photoinduced electron transfer (PET) can produce systems which exhibit restored fluorescence upon saccharide binding. For the past ten years, this approach has been championed by groups such as James et al.
10,13,17-19
and
ACS Paragon Plus Environment
2
Page 3 of 36 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
ACS Applied Materials & Interfaces
Badugu, et al. In solution, demonstration of this effect is relatively straightforward, but upon 4,16
transitioning to a polymeric matrix, maintaining the response can be significantly challenging.
20
In an indirect fluorescent sensing system, as pioneered by Singaram and co-workers,
21-28
the
fluorophore is typically negatively charged and the BA group appended to a separate cationic molecule. These molecules interact electrostatically to form a non-fluorescent ground-state 23
Upon saccharide binding, a conformational change around boron is induced and the
complex.
24,25
anionic boronate form is generated, resulting in dissociation in the ground-state complex and restoration of fluorescence. By employing a two-component system, the sensing approach can be 25
simplified through the design of small cationic BA derivatives. The resulting fluorescence response therefore relies on both the ability of the BA molecule to interact with the fluorophore and the subsequent binding of saccharides, to sufficiently disrupt this fluorescence quenching mechanism. Singaram et al. have demonstrated that for BA-substituted bipyridinium and 25
phenanthrolinium viologens, the substitution of the phenylboronic acid has a significant bearing on both fluorescence quenching and recovery. In particular, the ability of the cationic nitrogen to interact with the boron centre, can have a profound effect on the fluorescent response. When a N 25
+
B interaction is permitted, dissociation of the ground-state complex is believed to occur more -
effectively.
25
Using the same family of viologens, other groups have expanded on this work by variation of the fluorophore. Feng et al.
29,30
demonstrated two-component sensing systems in solution by
interchanging the fluorophore with a substituted naphthalene dye or a fluorescent BINOLcontaining polymer. Both approaches were most sensitive to glucose at lower concentrations (
