Organotin(IV) tryptophanylglycinates: potential non-steroidal antiinflammatory agents; crystal structure of dibutyltin(IV) tryptophanylglycinate

Diorganotin(IV) derivatives of tryptophanylglycine (H(2)Trp-Gly) with general formula R2Sn(Trp-Gly), where R = Me, n-Bu, Ph and n-Oct, and triorganotin(IV) derivatives R-3' Sn(HTrp-Gly) where R' = Me, n-Bu and Ph, have been synthesized and structurally characterized in the 'solid state as well as in solution on the basis of various spectroscopic techniques, viz. FT-IR, multinuclear H-1, C-13 and Sn-119 NMR, Sn-119 Mossbauer and single crystal X-ray diffraction. These investigations suggest that tryptophanylglycine in R2Sn(Trp-Gly) acts as dianionic tridentate coordinating through carboxylate oxygen [-C(O)O-], amino nitrogen (-NH2) and N-peptide(-), while in the case of R-3' Sn(HTrp-Gly), the ligand acts as monoanionic bidentate coordinating through -C(O)O- and -NH2. This is further confirmed by the single-crystal X-ray structure of n-Bu2Sn(Trp-Gly) which shows that two butyl groups and peptide nitrogen (N-Peptide(-)) are in the equatorial positions, while the two axial positions are occupied by the carboxylic oxygen [C(O)O-] and the amino nitrogen (NH2) atom from the same ligand molecule in the distorted trigonal-bipyramidal geometry around tin. The anti-inflammatory (using the carrageenan-induced paw edema bioassay in rats), cardiovascular activities and acute toxicity (LD50) of some of these compounds have been examined. All of the studied R2Sn(Trp-Gly) and Ph3Sn(HTrp-Gly) exhibit very high anti-inflammatory activities comparable to that of phenylbutazone along with high safety margin (LD50 > 400 mg kg(-1)) with no side effects on the cardiovascular system. Copyright (C) 2009 John Wiley & Sons, Ltd.