Structural and conformational study of substituted triazines by 15N NMR and x-ray analysis

Since the discovery of the multi-drug resistance (MDR) phenotype, reversant agents of various origins and structures have been extensively studied. In the present work, two series of related 2,4,6-tris(amino)-s-triazines with different MDR potential(1) were studied by N-15 NMR spectroscopy. The N-15 nucleus allows an easy identification of two protonation sites and an estimation of the electronic effects. N-15 was further found to be well suited to demonstrate the occurrence at room temperature of restricted rotation around the Ar-N bonds between the amino substituents and the s-triazine ring and to measure the rotational barriers. Crystal structures were determined by x-ray analysis of the compounds at various stages of protonation. The effects of the protonation at the sterically less hindered nitrogen of the triazine, detected by the NMR study, were confirmed in the solid-state structures. In the crystals, the orientation of the N-H and N-C bonds of the NHallyl substituent with respect to the triazine ring does not depend on the protonation state and corresponds to one of the conformations postulated in solution. (C) 1998 John Wiley & Sons Ltd.