Contribution of Weak S–H···O Hydrogen Bonds to the Side Chain Motions in d,l-Homocysteine on Cooling

Sulfhydryl groups play an important role in the formation of native structures of proteins and their biological functions. In the present work, we report for the first time the crystal structure of d,l-homocysteine and the results of a detailed study of the dynamics of its sulfhydryl group on cooling by precise single-crystal X-ray diffraction combined with polarized Raman spectroscopy of oriented single crystals. Although the crystal structures of both d,l-cysteine and d,l-homocysteine are layered, hydrogen bonds formed by −SH groups differ. In contrast with the crystal structure of d,l-cysteine with weak S–H···S hydrogen bonds between layers, d,l-homocysteine resembles the structures of amino acids with hydrophobic aliphatic side chains with no hydrogen bonds between the layers. The side chain of d,l-homocysteine forms a three-centered S–H···O hydrogen bond with carboxylate groups of two neighboring zwitterions. On cooling down, despite the shortening of the two S···O distances in the bifurcated S–H···O hydrogen bond, the wavenumber of the stretching vibrations of −SH groups increases. The same effect was also observed previously for other sulfhydryl containing amino acids, l-cysteine, and <i>N</i>-acetyl-l-cysteine on increasing pressure and is related to the strengthening of a three-centered bifurcated S–H···O hydrogen bond

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

The effect of hydrostatic pressure on single crystals of <i>N</i>-acetyl-l-cysteine was followed at multiple pressure points from 10^–4 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

CCDC 773689: Experimental Crystal Structure Determination

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures

CCDC 710543: Experimental Crystal Structure Determination

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures

CCDC 710540: Experimental Crystal Structure Determination

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures

CCDC 710539: Experimental Crystal Structure Determination

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures

CCDC 710537: Experimental Crystal Structure Determination

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures

CCDC 710542: Experimental Crystal Structure Determination

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures

CCDC 710541: Experimental Crystal Structure Determination

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures

CCDC 710538: Experimental Crystal Structure Determination

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures