Sugar Sensing Using Boronic Acid Modified Poly(amidoamine) Dendrimers. Xiaoli Liang

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1 Sugar Sensing Using Boronic Acid Modified Poly(amidoamine) Dendrimers Xiaoli Liang

2 Waste water in sweetener industry lactose glucose sucrose fructose maltose

3 Synthetic Sensors for carbohydrates Synthetic Sensors sensor Cannot overcome the high solvation enthalpies of sugars Limited selectivity Poor solubility in water Ramon, M.; Rolland, F.; Sheen, J. Arabidopsis Book 2008, 6, e0117. Wu, X.; Li, Z.; Chen, X. X.; Fossey, J. S.; James, T. D.; Jiang, Y. B. Chem. Soc. Rev. 2013, 42 (20),

4 Boronic acid diol interaction Acidic Basic Wu, X.; Li, Z.; Chen, X. X.; Fossey, J. S.; James, T. D.; Jiang, Y. B. Chem. Soc. Rev. 2013, 42 (20),

5 Indicator Displacement Assay (IDA) Alizarin Red S (ARS) A = C B MeOH Springsteen, G.; Wang, B. Tetrahedron 2002, 58,

6 Generating a sugar recognition system D fructose D ribose D glucose D galactose Sugar A Sugar B Fingerprint of Sugar A Array with receptors and dyes Fingerprint of Sugar B

7 PAMAM dendrimer Poly(amidoamine) (PAMAM) dendrimers as supramolecular hosts: 1. Commercially available 3. Ability to control end-group functionality 2. Large globular structure 4. High loading capacity G 1 G 0 core Gen. M w Diam. -NH 2 G3 6.9 kda 36 Å 32 G kda 45 Å 64 G kda 54 Å 128 G kda 67 Å 256

8 Boronic acid modified PAMAM In aqueous solution n PAMAM PAMAM + 2n dye D glucose [PAMAM ba dye] [PAMAM ba sugar]

9 Synthesis of the receptors G3 PAMAM 4 Åmolecular sieve MeOH, reflux, 3 d G3 PAMAM 32 NH 2 on the surface NaBH 4, MeOH, 24 h Yield PAMAM m ba = 68.3% Yield PAMAM o ba = 30.2% G3 PAMAM

10 Common Dyes with Diol Functional Group 4 Methylesculetin (ML) Alizarin Red S (ARS) Alizarin Complexone (AC) Pyrogallol Red (PGR) Pyrocatechol Violet (PV)

11 Alizarin Red S (ARS) + PAMAM-ba PAMAM ( ARS ) PAMAM Intensity PAMAM m ba Intensity PAMAM o ba [PAMAM-m-ba] ( M) (μm) [PAMAM-o-ba] ( M) (μm)

12 4-Methylesculetin (ML) + PAMAM-ba PAMAM ( ML ) PAMAM I/I PAMAM m ba [PAMAM-m-ba] ( M) (μm) Anisotropy I/I PAMAM o ba (μm) [PAMAM-o-ba] ( M) Anisotropy

13 Sugar binding at neutral ph PAMAM m ba G3 PAMAM Anisotropy conc. of fructose (mm) G3 PAMAM ML ML ph = 7.4 HEPES buffer; [ML] = M; [receptor] = M; λ ex = 362 nm; λ em = 450 nm.

14 Binding at ph 7.4 and 10.0 Anisotropy ph 7.4 ph 10.0 Anisotropy conc. of fructose (mm) conc. of fructose (mm) [ML] = M; [mba] = M; λ ex = 362 nm; λ em = 450 nm.

15 Displacement at ph 10.0 Anisotropy fructose Anisotropy ribose conc. of fructose (mm) conc. of ribose (mm) Anisotropy glucose Anisotropy galactose conc. of glucose (mm) conc. of galactose (mm)

16 Comparison of sugar binding [mba ML] [mba ARS] glucose fructose ribose galactose I/I I/I conc. of sugars (mm) conc. of sugars (mm)

17 Fingerprinting setup [sugar] = 2.00 mm [ARS] = 51.4 μm [ML] = 10.3 μm [mba] = 433 μm [oba] = 264 μm Sugars + [mba ARS] ph 7.4/10.0 Sugars + [mba ML] ph 7.4/10.0 Sugars + [oba ARS] ph 7.4/10.0 Sugars + [oba ML] ph 7.4 absorbance 9x spectral features collected: fluorescence intensity fluorescence anisotropy 334 nm 380/450 nm 380/450 nm 362 nm 516/580 nm 380 nm 384 nm 510 nm 700 nm plates/ ultravision plates 384 well and 96 well/

18 Linear Discriminant Analysis (LDA) 9factors: absorbance 510 nm 334 nm 362 nm 384 nm 700 nm 380 nm fluorescence intensity fluorescence anisotropy 380/450 nm 380/450 nm 516/580 nm % of total variance 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% ignored factors Original dataset: each data point is associated with 9 measured values 9 dimensional space Data reduction: How many of the new axes can I ignore while still capturing most of the original information?

19 Separation of four monosaccharides Reduce the 9 dimensional data to 2 dimensional data while remain 97.9% of data information D ribose % of total variance 90% 80% 70% 60% 50% 40% Factor % Factor 2 (19.3%) D galactose D glucose D fructose 30% 20% 10% Factor % 0% factors Factor 1 (78.6%) X. Liang, M. Bonizzoni. J. Mater. Chem. B, 2016, 4,

20 OH Separation of four disaccharides D sucrose D lactose D trehalose D sucrose D lactose HO HO HO CH 2 OH O O HOH 2 C O OH D trehalose OH OH HOH 2 C HO HO O CH 2 OH O O HO D maltose OH OH D maltose [sugar] = 30.0 mm; [ARS] = 514 μm; [ML] = 103 μm; [mba] = 434 μm; [oba] = 264 μm.

21 Conclusions A water soluble sugar recognition system was successfully generated. Both monosaccharide and disaccharide can be differentiated by the system. Future Work Sense other materials with diol groups (artificial sweeteners and polyphenols). Resolve mixtures.

22 Contact information Acknowledgements Dr. Ashley M. Jolly Dr. Alie M. Mallet Yifei Xu Dr. Marco Bonizzoni Nicholas J. White Michael H. Ihde Madyson Brown Graduate Council Fellowship Addison Iszler Cara Pridmore