A photo-induced three-component reaction of quinoxalin-2(1 H )-ones with unactivated alkenes and fluoroalkyl bromides has been developed. This transformation was initiated by the photochemistry of electron donor acceptor (EDA) complexes.

The reductions of Pt(iv) anticancer prodrugs [Pt(dach)Cl₄] (ormaplatin/tetraplatin) and cis-[Pt(NH₃)₂Cl₄] by several dominant reductants in human plasma have been characterized and analyzed kinetically and mechanistically.

Unprecedented EtOH-mediated cascade C(sp³)–H alkylation reactions of 4-dialkylamino-indole-3-carbaldehydes have been realized for the green and divergent synthesis of spirocyclic azepino[4,3,2-cd]indole derivatives.

The development of Pt(IV) anticancer prodrugs to overcome the detrimental side effects of Pt(II)-based anticancer drugs is of current interest. The kinetics and reaction mechanisms of the reductive activation of the carboplatin Pt(IV) prodrug cis,trans-[Pt(cbdca)(NH₃)₂Cl₂] (cbdca = cyclobutane-1,1-dicarboxylate) by the major small-molecule reductants in human plasma were analyzed in this work. The reductants included ascorbate (Asc), the thiol-containing molecules L-cysteine (Cys), DL-homocysteine (Hcy), and glutathione (GSH), and the dipeptide Cys–Gly. Overall second-order kinetics were established in all cases. At the physiological pH of 7.4, the observed second-order rate constants k′ followed the order Asc << Cys–Gly ~ Hcy < GSH < Cys. This reactivity order together with the abundances of the reductants in human plasma indicated Cys as the major small-molecule reductant in vivo, followed by GSH and ascorbate, whereas Hcy is much less important. In the cases of Cys and GSH, detailed reaction mechanisms and the reactivity of the various protolytic species at physiological pH were derived. The rate constants of the rate-determining steps were evaluated, allowing the construction of reactivity-versus-pH distribution diagrams for Cys and GSH. The diagrams unraveled that species III of Cys (⁻SCH₂CH(NH₃⁺)COO⁻) and species IV of GSH (⁻OOCCH(NH₃⁺)CH₂CH₂CONHCH(CH₂S⁻)- CONHCH₂COO⁻) were exclusively dominant in the reduction process. These two species are anticipated to be of pivotal importance in the reduction of other types of Pt(IV) prodrugs as well.

Captopril, the first pharmaceutical drug designed, synthesized, and used primarily for the treatment of hypertension and congestive heart failure, is an angiotensin-converting-enzyme inhibitor and is also an antioxidant. On the other hand, the kinetic and mechanistic aspects for the oxidation of captopril are not well understood. The oxidation of captopril by cisplatin prodrug and a model compound, cis-[Pt(NH₃)₂Cl₄] and trans-[PtCl₂(CN)₄]²⁻, was thus investigated in this work. A stopped-flow spectrometer was employed to follow the oxidation kinetics over a wide pH-range under the pseudo first-order conditions of [captopril] ≫ [Pt(IV)]. The oxidation by the Pt(IV) complexes displayed a second-order character, first-order each in [Pt(IV)] and in [captopril], whereas the metal-ion-catalyzed autooxidation made a very minor contribution to the overall kinetics in acidic media and was negligible in neutral media. Captopril was oxidized to form the captopril-disulfide as identified by ESI mass spectrometry under the conditions of the kinetic measurements. In the proposed reaction mechanism, the Pt(IV) complexes are reduced by the three protolytic captopril species in parallel as rate-determining steps, generating reactive species of chlorothiol and/or sulfenylchloride. The reactive species will be rapidly trapped, either directly or indirectly, by another molecule of captopril to form captopril-disulfide. The rate constants for the rate-determining steps have been derived, demonstrating that the fully deprotonated captopril is about 10⁵ to 10⁶ times more reactive than its corresponding thiol form toward the Pt(IV) complexes.