Proline residues within proteins lack a traditional hydrogen bond donor. However, the hydrogens of the proline ring are all sterically accessible, with polarized C−H bonds at Hα and Hδ that exhibit greater partial positive character and can be utilized as alternative sites for molecular recognition. C−H/O interactions, between proline C−H bonds and oxygen lone pairs, have been previously identified as modes of recognition within protein structures and for higher‐order assembly of protein structures. In order to better understand intermolecular recognition of proline residues, a series of proline derivatives was synthesized, including 4
Crystal structure of zymonic acid and a redetermination of its precursor, pyruvic acid
The structure of zymonic acid (systematic name: 4-hydroxy-2-methyl-5-oxo-2,5-dihydrofuran-2-carboxylic acid), C 6 H 6 O 5 , which had previously eluded crystallographic determination, is presented here for the first time. It forms by intramolecular condensation of parapyruvic acid, which is the product of aldol condensation of pyruvic acid. A redetermination of the crystal structure of pyruvic acid (systematic name: 2-oxopropanoic acid), C 3 H 4 O 3 , at low temperature (90 K) and with increased precision, is also presented [for the previous structure, see: Harata et al. (1977). Acta Cryst. B 33 , 210–212]. In zymonic acid, the hydroxylactone ring is close to planar (r.m.s. deviation = 0.0108 Å) and the dihedral angle between the ring and the plane formed by the bonds of the methyl and carboxylic acid carbon atoms to the ring is 88.68 (7)°. The torsion angle of the carboxylic acid group relative to the ring is 12.04 (16)°. The pyruvic acid molecule is almost planar, having a dihedral angle between the carboxylic acid and methyl-ketone groups of 3.95 (6)°. Intermolecular interactions in both crystal structures are dominated by hydrogen bonding. The common R 2 2 (8) hydrogen-bonding motif links carboxylic acid groups on adjacent molecules in both structures. In zymonic acid, this results in dimers about a crystallographic twofold of space group C 2/ c , which forces the carboxylic acid group to be disordered exactly 50:50, which scrambles the carbonyl and hydroxyl groups and gives an apparent equalization of the C—O bond lengths [1.2568 (16) and 1.2602 (16) Å]. The other hydrogen bonds in zymonic acid (O—H...O and weak C—H...O), link molecules across a 2 1 -screw axis, and generate an R 2 2 (9) motif. These hydrogen-bonding interactions propagate to form extended pleated sheets in the ab plane. Stacking of these zigzag sheets along c involves only van der Waals contacts. In pyruvic acid, inversion-related molecules are linked into R 2 2 (8) dimers, with van der Waals interactions between dimers as the only other intermolecular contacts.
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- Award ID(s):
- 1255290
- NSF-PAR ID:
- 10107211
- Date Published:
- Journal Name:
- Acta Crystallographica Section E Crystallographic Communications
- Volume:
- 75
- Issue:
- 6
- ISSN:
- 2056-9890
- Page Range / eLocation ID:
- 858 to 862
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Abstract R ‐hydroxyproline nitrobenzoate methyl ester, acylated on the proline nitrogen with bromoacetyl and glycolyl groups, and Boc‐4S ‐(4‐iodophenyl)hydroxyproline methyl amide. All three derivatives exhibited multiple close intermolecular C−H/O interactions in the crystallographic state, with H⋅⋅⋅O distances as close as 2.3 Å. These observed distances are well below the 2.72 Å sum of the van der Waals radii of H and O, and suggest that these interactions are particularly favorable. In order to generalize these results, we further analyzed the role of C−H/O interactions in all previously crystallized derivatives of these amino acids, and found that all 26 structures exhibited close intermolecular C−H/O interactions. Finally, we analyzed all proline residues in the Cambridge Structural Database of small‐molecule crystal structures. We found that the majority of these structures exhibited intermolecular C−H/O interactions at proline C−H bonds, suggesting that C−H/O interactions are an inherent and important mode for recognition of and higher‐order assembly at proline residues. Due to steric accessibility and multiple polarized C−H bonds, proline residues are uniquely positioned as sites for binding and recognition via C−H/O interactions. -
Two bis-carbamoylmethylphosphine oxide compounds, namely {[(3-{[2-(diphenylphosphinoyl)ethanamido]methyl}benzyl)carbamoyl]methyl}diphenylphosphine oxide, C 36 H 34 N 2 O 4 P 2 , (I), and diethyl [({2-[2-(diethoxyphosphinoyl)ethanamido]ethyl}carbamoyl)methyl]phosphonate, C 14 H 30 N 2 O 8 P 2 , (II), were synthesized via nucleophilic acyl substitution reactions between an ester and a primary amine. Hydrogen-bonding interactions are present in both crystals, but these interactions are intramolecular in the case of compound (I) and intermolecular in compound (II). Intramolecular π–π stacking interactions are also present in the crystal of compound (I) with a centroid–centroid distance of 3.9479 (12) Å and a dihedral angle of 9.56 (12)°. Intermolecular C—H...π interactions [C...centroid distance of 3.622 (2) Å, C—H...centroid angle of 146°] give rise to supramolecular sheets that lie in the ab plane. Key geometric features for compound (I) involve a nearly planar, trans- amide group with a C—N—C—C torsion angle of 169.12 (17)°, and a torsion angle of −108.39 (15)° between the phosphine oxide phosphorus atom and the amide nitrogen atom. For compound (II), the electron density corresponding to the phosphoryl group was disordered, and was modeled as two parts with a 0.7387 (19):0.2613 (19) occupancy ratio. Compound (II) also boasts a trans -amide group that approaches planarity with a C—N—C—C torsion angle of −176.50 (16)°. The hydrogen bonds in this structure are intermolecular, with a D ... A distance of 2.883 (2) Å and a D —H... A angle of 175.0 (18)° between the amide hydrogen atom and the P=O oxygen atom. These non-covalent interactions create ribbons that run along the b -axis direction.more » « less
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1107/S2056989019007072
