DFT Study of Coordination of N-Monochlorosubstituation Derivatives of Biguanide

Biguanides [HN=C(NR1R2)-NH-C(NR3R4)=NH] constitute an important family of molecules used as drugs in the treatment of diabetes. It is known that some transition metal complexes with given organic compounds deeply increase both therapeutic actions of the metal and the organic compound. The chlorine atom, a preferred substitute in pharmacy, improves the effectiveness of drugs and reduces their side effects. The mesmeric +M effect of the chlorine atom would make it possible to enhance the nucleophilic character of any N-chlorosubstituted nitrogen. In this work a theoretical study of coordination of N-chlorine derivatives of biguanide is carried out mainly at the DFT/B3LYP/6-31G (d, p) level. The Gaussian 09 & 03, HyperChem softwares and the DCENT-QSAR program are used. The coordinating possibility of each ligand were studied analyzing some coordinating indicators as: interatomic bond lengths, atomic charges, molecular electrostatic potentials, frontier orbital structures and electrophilic superdelocalizability. Then, the formation of its complex with zinc (II) has been calculated. The results of the calculations revealed the imine nitrogen atoms as the most favorable coordination sites. Bioactive complexes of these ligands with Zn (II) are modelled. Testing the bioavailability of obtained complexes according to the Lipinski rules of 5, we noticed that they can be considered as drug-candidates.