Antimicrobial Activity with Enhanced Mechanical Properties in Phenylalanine-Based Chiral Coassembled Hydrogels: The Influence of Pyridine Hydrazide Derivatives

Abstract

Hydrazide derivatives are known to display a wide range of biological properties including antimicrobial activities, hence making them desirable candidates for soft biomaterials. Herein, we report chiral supramolecular coassembled hydrogels obtained from two phenylalanine gelators (L/DPF and B2L/D) and two dicarbohydrazide molecules (pyridine-2,6-dicarbohydrazide (PDH) and (2,2′-bipyridine)-5,5′-dicarbohydrazide (BDH)) that exhibited enhanced mechanical properties, chirality modulation, and antimicrobial activity. Four lines of coassembled hydrogels were obtained (i.e., L/DPF–PDH, L/DPF–BDH, B2L/D–PDH, and B2L/D–BDH) through hydrogen bonding and π–π stacking with some level of an interpenetrating network, as revealed by the structural characterization analysis. Mechanical properties were significantly improved, especially in the case of hybrid gels involving BDH, with improved average elastic modulus (G′) values of 3430 and 3167 Pa for DPF–BDH and B2D–BDH (1:3, molar concentration) over 140 and 1680 Pa for DPF and B2D gelators, respectively. This was attributed to the improved π–π stacking and interpenetrating network due to the bipyridine group and its ease to form fibrous precipitates in the process of heating and cooling to room temperature. PDH, on the other hand, was able to modulate chirality in the L/DPF gelator due to its more planar and less bulky nature and showed antimicrobial activity against Pseudomonas aeruginosa (Gram-negative). Interestingly, when PDH was coassembled with the B2L/D gelator, the hybrid gels exhibited antimicrobial activity against Staphylococcus aureus (Gram-positive) and P. aeruginosa (Gram-negative) by virtue of a synergistic effect of the gelator and the azomethine group of PHD. Hence, by moving from bipyridine (BDH) to pyridine (PDH) as a core structure in the hydrazide molecules, the resulting hybrid hydrogels exhibited desirable properties of antimicrobial activity and improved mechanical attributes.

Facile construction of a family of supramolecular gels with good levofloxacin hydrochloride loading capacity

“…This trait was endowed by the intrinsic dynamic reversible supramolecular interactions of gelators. 43,44 The G3 gel exhibited a higher mechanical strength in PEG400 than in PEG200 under the same concentration (Fig. 5D), which may have been caused by the hydrogen bonding of gelator molecules and PEG200 molecules being stronger than that of the gelator molecules and PEG400 molecules.…”

“…FT-IR spectroscopy was used to investigate the non-covalent bond interactions of gelators in the gelation process. 43,48 In the spectrum of the gelator 2f, the peaks at 3297.7 and 3433.8 cm À1 belong to the symmetrical and asymmetrical stretching vibrations of the N-H bond in the amino group, respectively (Fig. 3A).…”

“…Hydrazide and phenylalanine moieties may also confer the gels with potential antimicrobial activity. 33,43 With shear thinning and destruction-recovery properties, these levooxacin hydrochloride-loaded gels have huge potential application value as antimicrobial gels.…”

“…42 Feng et al developed phenylalanine-based chiral co-assembled hydrogels with enhanced mechanical properties and antimicrobial activity, which were prepared using a phenylalanine derivative and a dihydrazide compound. 43 To the best of our knowledge, simultaneously taking advantage of phenylalanine and hydrazide groups to construct LMWGs for antimicrobial therapy has not been reported.…”

Construction of Polymeric Micelles for Improving Cancer Chemotherapy by Promoting the Production of Intracellular Reactive Oxygen Species and Self‐Accelerating Drug Release

“…[11] Wang et.al based on CA constructed an acidsensitive polyprodrug with cascade of ROS generation for combinational photodynamic therapy. [12] Zhang et.al. developed a nanoflowers by yolk-shell structured nanoparticles, CA, and hyaluronic acid, which could depleting GSH, inducing generation of ROS and shown combined antitumor effect of oxidative stress and photothermal.…”