Department of Organic Chemistry, Indian Institute of Science, Bengaluru, 560012, India.
Department of Biochemistry, Indian Institute of Science, Bengaluru, 560012, India.
Angew Chem Int Ed Engl. 2024 Jan 2;63(1):e202314804. doi: 10.1002/anie.202314804. Epub 2023 Nov 29.
Reversible biointerfaces are essential for on-demand molecular recognition to regulate stimuli-responsive bioactivity such as specific interactions with cell membranes. The reversibility on a single platform allows the smart material to kill pathogens or attach/detach cells. Herein, we introduce a 2D-MoS functionalized with cationic azobenzene that interacts selectively with either Gram-positive or Gram-negative bacteria in a light-gated fashion. The trans conformation (trans-Azo-MoS ) selectively kills Gram-negative bacteria, whereas the cis form (cis-Azo-MoS ), under UV light, exhibits antibacterial activity against Gram-positive strains. The mechanistic investigation indicates that the cis-Azo-MoS exhibits higher affinity towards the membrane of Gram-positive bacteria compared to trans-Azo-MoS . In case of Gram-negative bacteria, trans-Azo-MoS internalizes more efficiently than cis-Azo-MoS and generates intracellular ROS to kill the bacteria. While the trans-Azo-MoS exhibits strong electrostatic interactions and internalizes faster into Gram-negative bacterial cells, cis-Azo-MoS primarily interacts with Gram-positive bacteria through hydrophobic and H-bonding interactions. The difference in molecular mechanism leads to photo-controlled Gram-selectivity and enhanced antibacterial activity. We found strain-specific and high bactericidal activity (minimal bactericidal concentration, 0.65 μg/ml) with low cytotoxicity, which we extended to wound healing applications. This methodology provides a single platform for efficiently switching between conformers to reversibly control the strain-selective bactericidal activity regulated by light.
可还原生物界面对于按需分子识别至关重要,可用于调节刺激响应生物活性,例如与细胞膜的特异性相互作用。在单个平台上的可逆性允许智能材料杀死病原体或附着/脱离细胞。在此,我们介绍了一种二维二硫化钼,其功能化有阳离子型偶氮苯,可通过光门方式选择性地与革兰氏阳性菌或革兰氏阴性菌相互作用。反式构象(trans-Azo-MoS )选择性地杀死革兰氏阴性菌,而顺式构象(cis-Azo-MoS )在紫外光下对革兰氏阳性菌株表现出抗菌活性。机理研究表明,与 trans-Azo-MoS 相比,cis-Azo-MoS 对革兰氏阳性菌的膜具有更高的亲和力。对于革兰氏阴性菌,trans-Azo-MoS 比 cis-Azo-MoS 更有效地内化,并产生细胞内 ROS 来杀死细菌。虽然 trans-Azo-MoS 表现出强静电相互作用并更快地内化到革兰氏阴性细菌细胞中,但 cis-Azo-MoS 主要通过疏水和氢键相互作用与革兰氏阳性细菌相互作用。分子机制的差异导致光控革兰氏选择性和增强的抗菌活性。我们发现具有菌株特异性和高杀菌活性(最小杀菌浓度,0.65 μg/ml)且细胞毒性低的方法,我们将其扩展到伤口愈合应用中。该方法提供了一个单一平台,可在构象之间高效切换,以可逆地控制由光调节的菌株选择性杀菌活性。