Thermally Induced Self-Assembly and Cyclization of l-Leucyl-l-Leucine in Solid State

Abstract

Thermal treatment of oligopeptides is one of the methods for synthesis of organic nanostructures. However, heating may lead not only to self-assembly of the initial molecules, but also to chemical reactions resulting in the formation of new unexpected nanostructures or change in the properties of the existing ones. In the present work, the reaction of cyclization of dipeptide l-leucyl-l-leucine in solid state under heating was studied. The change in morphology of dipeptide thin film and formation of nanostructures after heating was visualized using atomic force microscopy. This method also was used for demonstration of differences in self-assembly of linear and cyclic dipeptides. The chemical structure of reaction product was characterized by NMR spectrometry, FTIR spectroscopy and GC-MS analysis. Kinetic parameters of cyclization were estimated within the approaches of the nonisothermal kinetics ("model-free" kinetics and linear regression methods for detection of topochemical equation). The results of present work are useful for explanation the changes in the properties of nanostructures based on short-chain oligopeptides, notably leucyl-leucine, after thermal treatment, as well as for the synthesis of cyclic oligopeptides.

One Step up the Ladder of Prebiotic Complexity: Formation of Nonrandom Linear Polypeptides from Binary Systems of Amino Acids on Silica

“…In Leu/SiO 2 activated at 150 8C, the bands diagnostic of the carboxylate anda mmonium moieties essentially disappeared. Instead, new bands are apparent at 1657, 1469, 1392cm À1 ,a s well as at lower wavenumbers;b yc omparison with the solidstate spectrum reported in the literature, [43] the first two bands at least can be safely assigned to the cyclic dimer (diketopiperazine, or cyclo(Leu-Leu)),a nd the bands below 1400 cm À1 also appear compatible with that compound. Shoulders at 1710 and 1438 cm À1 are possibly related to the small-scale formation of ab yproduct (with the first one tentatively assigned to the C=Os tretching of aC OOH group).…”

“…Note that in the bulk cyclic dimer,w hile the amide Iv ibration is present (1657 cm À1 ), the amide II is absent from the 1500-1600 cm À1 region. [43][44] This absence of an amide II vibration rules out the presenceo f linear polypeptides in significant amounts.…”

Thermally induced cyclization of L‐isoleucyl‐L‐alanine in solid state: Effect of dipeptide structure on reaction temperature and self‐assembly

“…According to the MS curves obtained ( m / z = 17 and 18), this process is accompanied by the release of water. One can assume that there is a chemical reaction in the dipeptide phase, for example, cyclization of a dipeptide (Figure ) …”

“…In view of the significant importance of DKPs for various technologies, their preparation methods are actively developed, including the solid‐phase synthesis, microwave‐assisted cyclization of dipeptides in water, and solid‐state synthesis . The latter procedure allows to obtain DKPs in one step without any by‐products .…”

“…The latter procedure allows to obtain DKPs in one step without any by‐products . However, approaches to the study of solid‐state reactions involving biomolecules are relatively well developed only for amino acids, but insignificantly for dipeptides, from which required cyclic molecules can be obtained using heat treatment . This problem is mainly due to the fact that there are only a few clear examples of the solid‐state synthesis of DKPs from dipeptides in the literature, because generally the heating of dipeptides leads to their thermal decomposition, which nonetheless can mask the cyclization reaction.…”