Unraveling the sequence of electron flow along the cyclocondensation reaction between ciprofloxacin and thiosemicarbazide through the bonding evolution theory.

We have theoretically conducted a comprehensive investigation on the cyclocondensation reaction between ciprofloxacin and thiosemicarbazide at the MN15/6-311++G(d,p) level of approximation. In order to revisit and understand the sequence of electronic flow rearrangement, as described in terms of electron pair distribution, within the framework of Bonding Evolution Theory (BET) approach as provided by the application of Thom's elementary Catastrophe Theory (CT) to the changes, along the intrinsic reaction coordinate, of the gradient vector field of the electron localization function (ELF). This reaction has two channels (a and b) and each one takes place via three steps. The CDFT results show that ciprofloxacin and thiosemicarbazide have an electrophilic and nucleophilic characters respectively and therefore allowing this reaction to have a polar character. All the transition state (TS) of all reaction steps have been localized and characterized. In addition, the analysis of activation energy predicts the formation of ciprofloxacin thiosemicarbazone 3a (channels a) as a main product in good agreement with experimental outcomes. The BET analysis results along channel a reveal that the mechanism for each reaction step is divided into four structural stability domains. During the first step, a new N2-C2 bond occurs at the SSD-II, followed by a rupture of the H1-N2 single bond (SSD-III) illustrating the restoration of lone pairs of the N2 nitrogen atom, and finally, the formation of a new H1-O1 single bond. For the second step, the process involves the breaking of O1-C2 and N2-H3 bonds at the SSD-II and SSD-III, respectively, followed by the formation of O1-H3 bond at the SSD-IV. For the last step, it is noted the formation of C4-N8 bond at the SSD-II, followed by the breaking of N8-H9 and C4-O6 bonds simultaneously at the SSD-III with water elimination at the last domain (SSD-IV).