The quantum-chemical calculation of the electronic structures of thiosemicarbazide and its S-methyl derivative (MTSC) shows that the alkylation-induced changes in the configuration of thiosemicarbazide and changes in the coordination mode of its alkyl derivatives upon complexation with 3d metals are explained by a change in the electron density on the terminal nitrogen and sulfur atoms. The alkylation sharply reduces the negative charge on the sulfur atom, rendering the N(5) atom most nucleophilic in MTSC. Because of this, the formation of the M-N(5) bond becomes more preferable. However, the difference between the charges on the N(5) and N(1) atoms is small, so that the electrophilic attack on the N(1) atom cannot be ruled out under certain conditions. In this case, if the energy of rotation about the C(3)-N(2) axis is higher than the energy gain provided by the formation of the M-N(1) bond, the metallocycle closure can occur due to the coordination of the sulfur atom of thiomethyl group.