Carbene →N+ Coordination Bonds in Drugs: A Quantum Chemical Study

Coordination chemistry of bonds between main group elements and electron donating ligands as in L →E (where E is electron acceptor centre like C 0 , Si 0 , N 1 , P 1 , As 1 , B 1 and L is an electron donating N-heterocyclic carbene) has been recently gaining attention. Many important drugs have nitrogen atom as an electron acceptor center and can be represented by two general formulae: (L → N ←L) ⊕ and L →N-R. Divalent N 1 compounds possess two lone pairs at central nitrogen and low nucleophilicity associated with them is found to be of importance. In this article, electronic structure analysis of drug molecules like picloxydine, chlorhexidine, and moroxydine was performed at B3LYP/6-311 ++G(d,p) level of theory. Evaluation of electron localization function (ELF), molecular orbitals, charge density, nucleophilicity, proton affinity and complexation energy estimation confirms the presence of coordination bonds (L → N ←L) ⊕ in the above mentioned drug molecules in their cationic state. Further, electronic structure analysis of drugs like clonidine, apraclonidine, brimonidine and xylazine indicated the presence of electronic structure similar to L →N-R systems. Graphical Abstract Evaluation of electron localization function (ELF), molecular orbitals, charge density, nucleophilicity, proton affinity and complexation energy estimation confirm the presence of coordination bonds (L→N←L) ⊕ in the drug molecules like picloxydine, chlorhexidine and moroxydine in their cationic state. Further, electronic structure analysis of drugs like clonidine, apraclonidine, brimonidine and xylazine indicated the presence of electronic structure similar to L→N-R systems.