Dependence of the biological activity and mass spectrometric pattern on the structure peculiarities of the molecule of alkylating drug thiotepa.

Structural and electronic parameters of the chemotherapeutic alkylating drug thiotepa obtained by MNDO and MINDO/3 quantum mechanical calculations are used to explain some physical, chemical and biological properties of this compound. On the basis of the revealed difference between the preferential conformations of the thiotepa molecule in crystal and vacuum, a conclusion is made concerning the precautions in the choice of the appropriate molecular geometry in the search of structure-activity correlations. The theoretical data are also applied to the explanation of some peculiarities of soft ionization mass spectra of thiotepa, in particular its sensitivity to high field effects and the absence of protonation. The modeling of some reactions of thiotepa directly in the conditions of field ionization mass spectrometric experiment is discussed.