基于主客超分子构象控制的“特洛伊木马”型组装抗菌策略研究

细菌耐药性感染已成为全球关注的威胁人类健康的重大难题，开发抗菌新策略，避免抗菌剂在环境中的积累，对解决耐药性危机具有重大的科学和应用价值。本项目将通过精确控制主客超分子构象变化实现对分子自组装材料结构和抗菌功能的精准调控。拟从抗菌活性、组装能力、响应性三个方面设计并构筑基于糖头基阳离子抗菌剂和葫芦[n]脲的主客体系，充分认识pH和光照双重刺激下客体分子结构、主体空腔大小对主客超分子构象变化的不同响应特点，进而探索超分子构象变化控制的自组装体结构转化规律及抗菌性能的调控规律，建立分子-超分子-超分子构象-组装结构-抗菌性能之间多层次的构效关系，从而获得一系列高效安全的“特洛伊木马”型精准抗菌材料。该类材料处于关闭状态时对细菌保持高度的隐蔽性与亲和性，一旦启动开关，将对细菌进行精准高效杀灭，从而减轻了抗菌剂对环境的持续性压力，为从根本上解决细菌耐药性问题提供一个行之有效的策略。

Antimicrobial drug resistance represents a global health emergency and it is of great scientific and practical value to develop new antibacterial strategies and avoid accumulation of active antibiotics in the environment. In this project, we hope to manipulate the structure and function of molecular self-assembled materials through precise control over the host-guest supramolecular conformation. The host-guest systems based on cationic antibiotics containing sugar head groups and cucurbit[n]urils will be designed and constructed from three aspects: antibacterial activity, assembly ability and responsiveness. We hope to fully understand the transformation rule of self-assembly structure controlled by the change of host-guest supramolecular conformation and its effect on the antibacterial activity under the dual stimulation of pH and light, and to establish the structure-activity relationship of “molecule-supramolecular-supramolecular conformation-assembly structure-antibacterial performance”, so as to obtain a series of efficient and safe "Trojan horse" antibacterial materials. This kind of material maintains a high degree of concealment and affinity for bacteria when the antibacterial switch is off. Once the switch is turned on, the bacteria will be killed accurately and efficiently, thus reducing the continuous pressure of antibacterial agents on the environment, and providing an effective strategy to fundamentally solve the problem of bacterial resistance.