Theoretical Study of Some Nitrososulfamide Compounds with Antitumor Activity 英文参考文献.docVIP

Molecules 2004, 9, 883-893 molecules ISSN 1420-3049 Theoretical Study of Some Nitrososulfamide Compounds with Antitumor Activity Khatmi Djameleddine*, Seridi Soumeya and Madi Fatiha Laboratory of Applied Chemistry, Guelma University, BP: 401, 24000, Guelma, Algeria * Author to whom correspondence should be addressed; E-mail: suila_djamel@yahoo.fr Received: 25 March 2004 / Accepted: 21 July 2004 / Published: 30 September 2004 Abstract: The lowest-energy conformations of four 2-chloroethylnitrososulfamides were determined using the MM+ molecular mechanics method as implemented in Hyperchem 6.0. Some of the calculated structural parameters, angles and bonds lengths were compared with the crystal structure data of N-nitroso-N-(2-chloroethyl)-N’-sulfamoyl- proline. Using MM+, AM1 and PM3 the anti conformation was predicted to be more stable than the syn conformation in each of these compounds. With these methods we found that the relative energy of the transition state (TS) was considerably higher, but with the ab initio method using RHF with minimal basic function STO-3G we found that the syn conformation is predicted to be slightly more stable. The determination of some atomic charges of a selection of atoms on the syn, anti and TS structures of the various compounds provided some details about the nature of the transition state. Keywords: Nitrososulfamides; Molecular modelling; syn conformation; anti conformation; Transition state. Introduction Until now, nitrosourea compounds have been considered some of the most powerful alkylating agents used in the chemotherapy, but they present the disadvantage of releasing isocyanate, a very toxic product, which limits their use [1]. It has been shown that this problem can be avoided by  Molecules 2004, 9 884 synthesizing a new family of compounds in which the nitrosourea function is replaced by the sulfonyl group [2]. It has also