Phosphorus–nitrogen compounds: part 70. Syntheses of tetraaminomono/bis(4-fluorobenzyl)spiro(N/N)cyclotriphosphazenes: structural characterization, Hirshfeld surface analysis and comparative evaluation of esterase activities of hCA I and hCA II isoenzymes

Abstract

Both starting phosphazenes, tetrachloromono- and tetrachlorobis-(4-fluorobenzyl)monospiro(N/N)cyclotriphosphazenes (1 and 2) were synthesized by the substitution reactions of hexachlorocyclotriphosphazene, N₃P₃Cl₆ (trimer; HCCP) with N-(4-fluorobenzyl)-1,3-diaminopropane (L1) and N,N′-bis(4-fluorobenzyl)-1,3-diaminopropane (L2), respectively. Tetraaminomono-(1a and 1b) and bis-(4-fluorobenzyl)spiro(N/N)cyclotriphosphazenes (2a and 2b) were prepared by the condensation reactions of spiro 1 and 2 with the excess of ethyl piperazine and phenylpiperazine, respectively, in boiling THF. Elemental analysis, FTIR, ESI-MS, ³¹P, ¹³C and ¹H NMR data identified the structures of the new products. In addition, the solid-state structure of 2b was confirmed by X-ray crystallography. Hirshfeld surface analysis of 2b indicates that the most important contributions for the crystal packing are from H⋯H (61.2%), H⋯C/C⋯H (24.8%) and H⋯F/F⋯H (9.3%) interactions. On the other hand, the inhibitory effects of these cyclotriphosphazenes on the esterase activities of hCA I and hCA II isoenzymes were investigated in vitro. It was determined that compound 2b exhibited a stronger inhibitory effect than compound 2a.