A comprehensive DFT study on organosilicon-derived fungicide flusilazole and its germanium analogue: A computational approach to Si/Ge bioisosterism

Bioisosterism, a specific molecular alteration processing, is an effective approach used in agrochemical development studies as well as in pharmaceutical sciences. Analyzing some parameters such as size, volume, charge, aqueous/lipid solubility, polarizability, degree of hybridization, intra- and intermolecular interactions, which may be caused by bioisosteric changes, by using quantum chemical methods, provides speed and different perspectives to the studies. Towards this end, this study approached the Si/Ge bioisosterism from a computational perspective by performing DFT-based calculations on flusilazole, a widely used fungicide, and its germanium analogue. The reflections of the replacement of silicon with germanium in the structure of flusilazole on the structural parameters, frontier molecular orbital energies, quantum chemical descriptors and electrostatic surface properties were examined. Additionally, FT-IR spectra of the aforementioned molecules were visualized and investigated in detail. Natural bond orbital analyzes were also performed to determine the intermolecular interactions and their corresponding stabilization energies. Besides, 1-octanol/water partition coefficients (logP_ow), the quantitative identifier of lipophilicity, were calculated. It was determined that both molecules could exhibit similar lipophilic character with a difference of 0.09 logarithmic units in logP_ow value.