Weak Hydrogen
Bonds Formed by Thiol Groups in <i>N</i>‑Acetyl‑l‑Cysteine and Their Response to the Crystal Structure
Distortion on Increasing Pressure
- Publication date
- Publisher
Abstract
The effect of hydrostatic pressure
on single crystals of <i>N</i>-acetyl-l-cysteine
was followed at multiple pressure points from 10<sup>–4</sup> to 6.2 GPa with a pressure step of 0.2–0.3 GPa by Raman
spectroscopy and X-ray diffraction. Since in the crystals of <i>N</i>-acetyl-l-cysteine the thiol group is involved
in intermolecular hydrogen bonds not as a donor only (bonds S–H···O)
but also as an acceptor (bonds N–H···S), increasing
the pressure does not result in phase transitions. This makes a contrast
with the polymorphs of l- and dl-cysteine, in which
multiple phase transitions are observed already at relatively low
hydrostatic pressures and are related to the changes in the conformation
of the thiol side chains only weakly bound to the neighboring molecules
in the structure and thus easily switching over the weak S–H···O
and S–H···S hydrogen bonds. No phase transitions
occur in <i>N</i>-acetyl-l-cysteine with increasing
pressure, and changes in cell parameters and volume vs pressure do
not reveal any peculiar features. Nevertheless, a more detailed analysis
of the changes in intermolecular distances, in particular, of the
geometric parameters of the hydrogen bonds based on X-ray single crystal
diffraction analysis, complemented by an equally detailed study of
the positions of all the significant bands in Raman spectra, allowed
us to study the fine details of subtle changes in the hydrogen bond
network. Thus, as pressure increases, a continuous shift of the hydrogen
atom of the thiol group from one acceptor (a carboxyl group) to another
acceptor (a carbonyl group) is observed. Precise single-crystal X-ray
diffraction and polarized Raman spectroscopy structural data reveal
the formation of a bifurcated S–H···O hydrogen
bond with increasing pressure starting with ∼1.5 GPa. The analysis
of the vibrational bands in Raman spectra has shown that different
donor and acceptor groups start “feeling” the formation
of the bifurcated S–H···O hydrogen bond in different
pressure ranges. The results are discussed in relation to some of
the previously published data on the effect of high pressure on the
polymorphs of l-cysteine, dl-cysteine, and glutathione,
that show similarity with the effects reported here for <i>N</i>-acetyl-l-cysteine. The results obtained in this work allow
one to suggest new models for the pressure-induced structural rearrangements
in the whole family of cysteine-containing crystals