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

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 P2(1) 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.