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 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.