Phosphorus-Nitrogen compounds part 74. Syntheses of (p-dimethylamino)benzyl-spiro-(N/N)-cyclotriphosphazenes: Structural characterizations, bioactivity studies, DFT calculations and reactivity parameters

Abstract

Reactions of hexachlorocyclotriphosphazene (HCCP, N3P3Cl6), with equimolar amounts of N-methyl-N'-(p-dimethylaminobenzyl)-1,2-diaminoethane (1), N-ethyl-N'-(p-dimethyl-aminobenzyl)-1,2-diaminoethane (2), and N-methyl-N'-(p-dimethylaminobenzyl)-1,3-diami-nopropane (3) produced the corresponding tetrachloro-(p-dimethylaminobenzyl)spiro-(N/N)-cyclotriphosphazenes (4, 5, and 6), regioselectively. Tetrapyrrolidino (4a-6a), tetrapiperidino (4b-6b), tetramorpholinophosphazenes (4c and 6c), dichlorodimorpholinophosphazene (5c) and tetra-1,4-dioxa-8-azaspiro[4,5]decanophosphazenes (DASD) (4d-6d) were synthesized from Cl-substitution reactions of 4, 5 and 6 with excess pyrrolidine, piperidine, morpholine, and DASD, respectively. Their structures were elucidated by MS, FTIR, NMR and single crystal X-ray diffraction (for 4, 4b and 6a) techniques. Hirshfeld surface (HS) analyzes of 4, 4b, and 6a were performed to visualize intermolecular interactions in the crystals. In addition, according to the antimicrobial activity test results, compound 6b shows a better inhibitory effect on S. aureus ATCC 25923 G(+) (MİC: 78.1 µM) and C. tropicalis Y-12968 (MİC: 19.54 µM) microorganisms. The interactions of cyclotriphosphazenes with 5′-G/GATCC-3′ and 5′-A/AGCTT-3′ sequences of DNA were evaluated by examining BamHI and HindIII restriction enzyme digestion. The quantum chemical calculations of 4, 4b, and 6a were performed using DFT, and their experimental parameters were compared with the theoretical ones. Natural bond orbitals (NBOs) were determined and HOMO-LUMO energy gaps (Eg) were calculated as 3.55, 5.23, and 5.24 eV for 4, 4b, and 6a, respectively.