Cyclization of L-Leucyl-L-valine Dipeptide in the Crystal Phase under Non-Isоthermal Conditions

Thermal treatment of linear dipeptides in solid state makes it possible to obtain their cyclic analogues in high yield and without additional expenses. At the same time, such reactions occurring under the conditions of crystal lattice restrictions with the participation of molecules in the zwitterionic form have not been sufficiently studied. In this work, the cyclization reaction of the L-leucyl-L-valine dipeptide in the crystalline phase upon heating was studied. Using isoconversion kinetics approaches, a kinetic model describing this process was found, and kinetic parameters were calculated, including activation energy, Arrhenius factor, and reaction order. The enantiomeric purity of the resulting cyclic product was assessed. The self-assembly of linear and cyclic dipeptides on a solid substrate was studied. The results of the study will be useful in determining mechanisms of the cyclization reactions of dipeptides in the solid state, and can also be used in the development of effective and cost-efficient methods for the production of cyclic dipeptides.