Theoretical and Experimental Investigations of Anion-π Interactions in Inorganic and Biological Supramolecular Architectures

Supramolecular chemistry encompasses the interdisciplinary study of weak intermolecular forces which allows for access to sophisticated architectures and functionalities. One newly recognized supramolecular force that is becoming increasingly prevalent in theoretical, organic, inorganic and biological chemistry is the attractive interaction between an anion and an aromatic system, the anion-π interaction. By integrating theoretical and experimental methods, the nature and implications of anion-π interactions have been studied in inorganic and biological systems. In order to expand the library of anion-templated, supramolecular metallacyclic architectures previously reported by the Dunbar group, a semi-empirical model has been developed that accurately reproduces the reported metallacyclic frameworks and predicts metallacycles available from 18 templating anions, 15 transition metals, and 2 bridging ligands. By considering the degree of overlap between the anion and the π-system, the most ideal metallacyclic candidates have been identified for future experimental studies. A second computational study has employed DFT methods to explore the hierarchy of factors that direct to the supramolecular formation of Ag^I coordination complexes, polymers and extended networks. These causative factors include the transition metal, bridging ligand, anion and solvent. Anion-templated metallacyclic architectures were further considered as building blocks for the elaboration of extended superstructures. Complexation of the pentagonal building blocks with organic bridging ligands has led to symmetrical, ambiguous structures and reaction with a cyano-metallate bridging moiety has facilitated supramolecular transformation into the first acetonitrile-templated metallacyclic architecture containing reduced bridging ligands. Finally, the impact of the anion-π interaction on inhibition of malate synthase, an important protein in Mycobacterium tuberculosis, has been probed through DFT methods. An appropriate model active site from one inhibitor-bound protein crystal structure was employed as a structural template such that the binding interactions and orientation were reproduced with a high degree of accuracy. By screening potential molecules according to the propensity of each to participate in anion-π interactions, the pre-screened predictive method efficiently incorporates the anion-π interaction into a methodology for future drug design. This interdisciplinary exploration of the anion-π interaction has combined theoretical and experimental research to help unravel the complexities of supramolecular inorganic and biological systems, providing direction for future experimental efforts