Inorganic Materials & Catalysis (IMC) Division, CSIR-Central Salt & Marine Chemicals Research Institute, Gijubhai Badheka Marg, Bhavnagar-364002, Gujarat, India.
Academy of Scientific and Innovative Research (AcSIR), AcSIR Headquarters, CSIR-HRDC Campus, Ghaziabad-201002, UP, India.
J Mater Chem B. 2024 Sep 11;12(35):8767-8777. doi: 10.1039/d4tb01355g.
Membrane-targeting compounds are of immense interest to counter complicated multi-drug resistant infections. However, the broad-spectrum effect of such compounds is often unmet due to the surges of antibiotic resistance among majority of Gram-negative bacteria compared to Gram-positive species. Though amphiphiles, synthetic mimics of antimicrobial peptides , have been extensively explored for their potential to perturb bacterial membranes, small molecule-based supramolecular hydrogels have remained unexplored. The design of supramolecular hydrogels can be tuned on-demand, catering to desired applications, including facile bacterial membrane perturbation. Considering the strong biocidal properties of Ag-based systems and the bacterial membrane-targeting potential of appended primary amine groups, we designed self-assembled multicomponent supramolecular Ag(I)-hydrogels with urea and DATr (3,5-diamino-1,2,4-triazole) as ligands, which are predisposed for hydrogen bonding and interacting with negatively charged bacterial membranes at physiological pH. The synthesized supramolecular Ag(I)-hydrogels exhibited almost similar antibacterial activity against both Gram-negative (; ) and Gram-positive (; ) bacteria, with minimal inhibitory concentration (MIC) of ∼60 μg mL. Ag(I)-hydrogels facilitated the disruption of the negatively charged bacterial membrane due to electrostatic interaction and complementary hydrogen bonding facilitated by DATr and urea. Sustained intracellular ROS generation in the presence of Ag(I)-hydrogel further expedited cell lysis. We envisage that the multicomponent supramolecular Ag(I)-hydrogels studied herein can be employed in designing effective antibacterial coatings on a range of medical devices, including surgical instruments. Moreover, the present form of the hydrogels has the potential to improve the antibacterial functionality of conventional antimicrobials, thus revitalizing the effective targeting of hard-to-treat multi-drug-resistant (MDR) bacterial infections in a clinical set up.
靶向膜的化合物对于对抗复杂的多药耐药感染非常重要。然而，由于与革兰氏阳性菌相比，大多数革兰氏阴性菌的抗生素耐药性不断增加，因此这些化合物的广谱效果往往无法实现。尽管两亲性物质（抗菌肽的合成模拟物）已被广泛探索用于其破坏细菌膜的潜力，但基于小分子的超分子水凝胶仍未得到探索。超分子水凝胶的设计可以按需进行调整，以满足包括易于破坏细菌膜在内的各种应用需求。考虑到基于银的系统具有很强的杀菌性能，以及附加的伯胺基团对靶向细菌膜的潜力，我们设计了具有尿素和 DATr（3,5-二氨基-1,2,4-三唑）作为配体的自组装多组分超分子 Ag（I）-水凝胶，这些配体易于形成氢键并在生理 pH 下与带负电荷的细菌膜相互作用。合成的超分子 Ag（I）-水凝胶对革兰氏阴性菌（ ）和革兰氏阳性菌（ ）均表现出几乎相似的抗菌活性，最小抑菌浓度（MIC）约为 60 μg mL。Ag（I）-水凝胶由于静电相互作用和 DATr 和尿素促进的互补氢键，促进了带负电荷的细菌膜的破坏。在存在 Ag（I）-水凝胶的情况下，持续产生的细胞内 ROS 进一步加速了细胞裂解。我们设想，本文研究的多组分超分子 Ag（I）-水凝胶可用于设计一系列医疗设备（包括手术器械）上的有效抗菌涂层。此外，水凝胶的现有形式有可能增强传统抗菌剂的抗菌功能，从而在临床环境中重新激活针对难以治疗的多药耐药（MDR）细菌感染的有效靶向治疗。
