CENTRO DE QUIMICA INORGANICA "DR. PEDRO J. AYMONINO"
Unidad Ejecutora - UE
A combined theoretical and spectroscopic study of 4,6-di-O-acetyl-2,3-dideoxy-D-erythro-hex-2-enopyranosylsulfamide: a novel glycosyl carbonic anhydrase IX inhibitor
MARTÍN J. LAVECCHIA; REINALDO PIS DIEZ; PEDRO A. COLINAS
ELSEVIER SCI LTD
Lugar: Amsterdam; Año: 2011 vol. 346 p. 442 - 442
The novel 4,6-di-O-acetyl-2,3-dideoxy-D-erythro-hex-2-enopyranosyl sulfamide, which exhibits selectivity for inhibiting isoform IX of carbonic anhydrase as overexpressed in many tumors, has been investigated from a combined theoretical and spectroscopic point of view. The conformational study of the compound shows that the alpha-anomeric form is more stable than the beta-anomeric form from a thermodynamic point of view after including solvent effects. This fact suggests that the synthesis reaction could take place mainly under thermodynamic control as the main experimental product is the alpha-anomeric form of the sulfamide. Calculated alpha/beta ratio is about 95:5, in excellent agreement with experimental data. Optimized geometries of the alpha-anomeric form agree quite well with crystallographic data. The inclusion of solvent has negligible effects on the conformations. A detailed analysis of some geometric parameters shed light into the conformational behavior of the sulfamide in terms of both exo- and endo-anomeric effects and antiperiplanar relationships. Natural bond orbital calculations confirm those findings. Several intramolecular hydrogen bonds, characterized through the Atoms-in-Molecules theory, were found in the stable conformers. They, however, seem to play no relevant role in determining the relative stability of alpha conformers with respect to the beta ones. Calculated 1H and 13C NMR chemical shifts support previous findings concerning configuration and conformation assignments of the title sulfamide. The IR spectrum of the compound is recorded and reported for the first time and the assignment of some of the most important bands is accomplished with the aid of calculated harmonic vibrational frequencies.