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Reports: ND751048-ND7: Hydrogels Based on Dynamic Covalently Linking and Crosslinking

Bing Gong, PhD, State University of New York at Buffalo

This grant supports the construction of linear polymers and polymeric networks for forming polymeric hydrogels by crosslinking hydrophobic and hydrophilic polymer chains using non-covalent and reversible covalent bonds. The association units are based on sequence-specific molecular duplexes that are equipped with both multiple hydrogen-bonding and disulfide bond-forming ability [1]. These duplexes, derived from H-bonded duplexes we developed [2-4], are capable of mediating highly specific association and covalent crosslinking in both nonpolar and polar (including aqueous) media [5, 6]. Our objectives are (1) modifying commercially available, biocompatible polymer chains such as poly(lactic acids) (PLA) and poly(ethylene glycol)(PEG) chains with our duplex-forming units, (2) forming libraries of amphiphilic dynamic covalent diblock, triblock and multi-block copolymers with various, readily adjustable PLA/PEG ratios mediated by the introduced duplex units, and (3) correlating the effect of PLA/PEG (thus the hydrophobic/hydrophilic) ratios on gelating ability of the resultant amphiphilic block copolymers.

In the second year, we have elucidated the conditions for coupling PLA and PEG chains of various lengths. PLA and PEG chains with molecular weights ranging from 1,000 to 5,000 end-modified with our duplex-forming units are successfully and efficiently coupled, leading to the formation of diblock and triblock copolymers. The resultant block  copolymers have been characterized with techniques including 1H NMR and GPC, results from which have demonstrated the expected high efficiency of our method. Figure 1a show the GPC traces of PEG5000-PLA5000, one of the diblock copolymers prepared.

Figure 1. (a) GPC traces of PEG5000-PLA5000 (red, retention time = 5.23 min), PEG5000 (blue, retention time = 5.57 min), and PLA5000 (black, retention time = 5.76 min) eluted with THF (1 mL/min) at 35 oC. (b) TEM image of PEG5000-PLA5000 micelles.

The obtained diblock copolymers were examined for their micellation in aqueous media. Dynamic light scattering (DLS) showed that the micelles all have unimodal size distribution, with average diameters ranging from 34 nm to over 100 nm. Transmission electron microscopy (TEM) demonstrated that the micelles are all spherical (Figure 1b). The polymeric micelles were stable for weeks in water. Upon adding a free thiol (DTT), the polymeric micelles disintegrate quickly due to the cleavage of disulfide linkages that connect that PEG and PLA blocks.

We have also started to ligate PEG and PLA chains into linear amphiphilic multiblock copolymers containing different ratios of the hydrophilic and hydrophobic blocks. The gelating ability of these multiblock copolymers are being assessed, with highly encouraging initial results. In the presence of branched crosslinkers, we have attempted the construction of crosslinked networks of hydrophilic polymer chains. Polymeric networks with different crosslinking densities have been prepared, based on which chemically crosslinked hydrogels with significantly enhanced mechanical stability are expected to be generated.

1. Gong, B. Molecular Duplexes with Encoded Sequences and Stabilities. Acc. Chem. Res. 2012, 45, 2077-2087.

2.     Gong, B.; Yan, Y.; Zeng, H.; Skrzypczak-Jankunn, E.; Kim, Y. W.; Zhu, J.; Ickes, H. A New Approach for the Design of Supramolecular Recognition Units: Hydrogen-Bonded Molecular Duplexes. J. Am. Chem. Soc. 1999, 121, 5607-5608.

3. Zeng, H.; Miller, R.; Flowers, R. A.; Gong, B. A Highly Stable, Six-Hydrogen Bonded Molecular Duplex. J. Am. Chem. Soc. 2000, 122, 2635-2644.

4. Zeng, H.; Ickes, H.; Flowers, II, R. A.; Gong, B. Sequence-Specificity of Hydrogen-Bonded Molecular Duplexes. J. Org. Chem. 2001, 66, 3574-3583.

5. Li, M. F.; Yamato, K.; Ferguson, J. S.; Gong, B. Sequence-Specific Intermolecular Association: Integrating Non-Covalent and Covalent Interactions. J. Am. Chem. Soc. 2006, 128, 16528-16529.

6.  Li, M. F.; Yamato, K.; Ferguson, J. S.; Singarapu, K. K.; Szyperski, T.; Gong, B. Sequence-Specific, Dynamic Covalent Crosslinking in Aqueous  Media. J. Am. Chem. Soc. 2008, 130, 491-500.