<Emphasis Type="Italic">Ab initio</Emphasis> DFT study of bisphosphonate derivatives as a drug for inhibition of cancer: NMR and NQR parameters

DFT computations were carried out to characterize the ¹⁷Oand ²H electric field gradient, EFG, in various bisphosphonate derivatives. The computations were performed at the B3LYP level with 6-311++G (d,P) standard basis set. Calculated EFG tensors were used to determine the ¹⁷O and ²H nuclear quadrupole coupling constant, χ and asymmetry parameter, η. For better understanding of the bonding and electronic structure of bisphosphonates, isotropic and anisotropic NMR chemical shieldings were calculated for the ¹³C, ¹⁷O and ³¹P nuclei using GIAO method for the optimized structure of intermediate bisphosphonates at B3LYP level of theory using 6-311++G (d, p) basis set. The results showed that various substituents have a strong effect on the nuclear quadrupole resonance (NQR) parameters (χ, η) of ¹⁷O in contrast with ²H NQR parameters. The NMR and NQR parameters were studied in order to find the correlation between electronic structure and the activity of the desired bisphosphonates. In addition, the effect of substitutions on the bisphosphonates polarity was investigated. Molecular polarity was determined via the DFT calculated dipole moment vectors and the results showed that substitution of bromine atom on the ring would increase the activity of bisphosphonates.