Cyclic Dipeptides as Building Units of Nano- and Microdevices: Synthesis, Properties, and Structural Studies

Abstract

In this paper we report the influence of stereochemistry on self-organization in the solid state of cyclic dipeptides (CDP) employing two diastereomeric samples cyclo­(l-Tyr-l-Ala), cYA 1, and cyclo­(l-Tyr-d-Ala), cY­(D)­A 2, as models. Both compounds were investigated by means of differential scanning calorimetry (DSC), solid state NMR (SS NMR) spectroscopy, scanning electron microscopy (SEM), powder X-ray diffraction (PXRD), electronic circular dichroism (ECD) spectroscopy, and attenuated total reflectance Fourier transform infrared spectroscopy (ATR–FTIR). It has been found that distinction in chirality of alanine residue causes a significant difference in self-assembling and formation of higher order structures. Sample 1 forms peptide nanotubes (PNT) and nanowires (PNW), while for sample 2 only formation of peptide microtubes (PMT) was observed. Crystal and molecular structures for 1 and 2 were refined using PXRD due to failure in attempts to grow crystals with quality suitable for single crystal studies. Both compounds crystallize in the P21 space group and monoclinic system. The size of the unit cell is highly similar; however small differences in alignment of water molecules in the hydrophilic channels and geometry of diketopiperazine rings were observed. Each technique confirmed high thermal stability of PNT, PNW, and PMT under investigation. The water molecules can be thermally removed from the lattice without destroying the subtle crystal structures of nano- and microdevices. This reversible process observed for sample 2 is a unique feature, rarely occurring for the linear dipeptide devices.

Vibrational circular dichroism of a 2,5‐diketopiperazine (DKP) peptide: Evidence for dimer formation in cyclo LL or LD diphenylalanine in the solid state

“…We have undertaken the study of dipeptides with identical or opposite chirality, both in the gas phase and in the condensed phase, with the aim of understanding how homo‐ or heterochirality of the residues impinges on their structure and can be identified by its spectroscopic signature . We shall focus here on cyclo diphenylalanine, denoted cyclo Phe‐Phe hereafter, which has attracted special attention due to its spontaneous formation by heating the parent Phe‐Phe linear dipeptide . Both cyclo LPhe‐LPhe and cyclo LPhe‐DPhe will be studied in the solid phase.…”

“…10,67 We shall focus here on cyclo diphenylalanine, denoted cyclo Phe-Phe hereafter, which has attracted special attention due to its spontaneous formation by heating the parent Phe-Phe linear dipeptide. 68,69 Both cyclo LPhe-LPhe and cyclo LPhe-DPhe will be studied in the solid phase. The presence of bulky aromatic rings is expected to introduce steric constraints and to increase stabilizing dispersive interactions within the peptide.…”

Modulating Hydrogen Bonded Self-assembled Patterns and Morphological Features by a Change in Side Chain of Third Amino Acid of Synthetic γ- Amino Acid Based Tripeptides

“…Conformational modulation and self‐assembled diversity of short peptides have been recently gained a considerable attention due to its immense importance in understanding the folding and self‐assembly of biomolecules. Conformational modulations in short hybrid peptides have been achieved by using various unnatural amino acids as constituents, chirality and by changing the N‐ and C‐terminal groups . Here, our objectives are (i) to probe the conformational modulation of two short peptides with sequences Boc‐Gpn‐Aib‐Xaa‐OMe (where Gpn=gabapentin, Xaa=Leu(L) for 1 and Phe(F) for 2 ) which varied only at C‐terminal residue both in solid as well as solution states (Scheme ), (ii) to explore the structural effects of backbone and side chain propensities in self‐assemble diversity of γαα‐based peptides 1 and 2 and (iii) to study the role of C‐terminal amino acids in the formation of diverse supramolecular self‐assemble morphological features.…”

Oxa–diketopiperazines: Access and Conformational Analysis of Potential Turn Inducers

“…Furthermore, to evaluate the impact of the presence of an oxygen atom on the conformation of the ring, the crystal structure of 3 a was compared to a cyclo (Tyr‐Ala)‐DKP analogue (Figure ) . Both heterocyclic structures were found to adopt a pseudo‐boat conformation with similar torsion angles, both aryl groups projecting toward similar directions, being overlapped in the oxa‐DKP or DKP ring.…”