skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Short Carboxylic Acid–Carboxylate Hydrogen Bonds Can Have Fully Localized Protons

Abstract

Short hydrogen bonds (H-bonds) have been proposed to play key functional roles in several proteins. The location of the proton in short H-bonds is of central importance, as proton delocalization is a defining feature of low-barrier hydrogen bonds (LBHBs). Experimentally determining proton location in H-bonds is challenging. Here, bond length analysis of atomic (1.15–0.98 Å) resolution X-ray crystal structures of the human protein DJ-1 and its bacterial homologue, YajL, was used to determine the protonation states of H-bonded carboxylic acids. DJ-1 contains a buried, dimer-spanning 2.49 Å H-bond between Glu15 and Asp24 that satisfies standard donor–acceptor distance criteria for a LBHB. Bond length analysis indicates that the proton is localized on Asp24, excluding a LBHB at this location. However, similar analysis of the Escherichia coli homologue YajL shows both residues may be protonated at the H-bonded oxygen atoms, potentially consistent with a LBHB. A Protein Data Bank-wide screen identifies candidate carboxylic acid H-bonds in approximately 14% of proteins, which are typically short [O–O> = 2.542(2) Å]. Chemically similar H-bonds between hydroxylated residues (Ser/Thr/Tyr) and carboxylates show a trend of lengthening O–O distance with increasing H-bond donor pK a. This trend suggests that conventional electronic effects provide an adequate explanation formore » short, charge-assisted carboxylic acid–carboxylate H-bonds in proteins, without the need to invoke LBHBs in general. This study demonstrates that bond length analysis of atomic resolution X-ray crystal structures provides a useful experimental test of certain candidate LBHBs.« less

Authors:
; ; ORCiD logo
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
USDOE; National Institutes of Health (NIH)
OSTI Identifier:
1339745
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemistry; Journal Volume: 56; Journal Issue: 2
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES; 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY

Citation Formats

Lin, Jiusheng, Pozharski, Edwin, and Wilson, Mark A. Short Carboxylic Acid–Carboxylate Hydrogen Bonds Can Have Fully Localized Protons. United States: N. p., 2017. Web. doi:10.1021/acs.biochem.6b00906.
Lin, Jiusheng, Pozharski, Edwin, & Wilson, Mark A. Short Carboxylic Acid–Carboxylate Hydrogen Bonds Can Have Fully Localized Protons. United States. doi:10.1021/acs.biochem.6b00906.
Lin, Jiusheng, Pozharski, Edwin, and Wilson, Mark A. Tue . "Short Carboxylic Acid–Carboxylate Hydrogen Bonds Can Have Fully Localized Protons". United States. doi:10.1021/acs.biochem.6b00906.
@article{osti_1339745,
title = {Short Carboxylic Acid–Carboxylate Hydrogen Bonds Can Have Fully Localized Protons},
author = {Lin, Jiusheng and Pozharski, Edwin and Wilson, Mark A.},
abstractNote = {Short hydrogen bonds (H-bonds) have been proposed to play key functional roles in several proteins. The location of the proton in short H-bonds is of central importance, as proton delocalization is a defining feature of low-barrier hydrogen bonds (LBHBs). Experimentally determining proton location in H-bonds is challenging. Here, bond length analysis of atomic (1.15–0.98 Å) resolution X-ray crystal structures of the human protein DJ-1 and its bacterial homologue, YajL, was used to determine the protonation states of H-bonded carboxylic acids. DJ-1 contains a buried, dimer-spanning 2.49 Å H-bond between Glu15 and Asp24 that satisfies standard donor–acceptor distance criteria for a LBHB. Bond length analysis indicates that the proton is localized on Asp24, excluding a LBHB at this location. However, similar analysis of the Escherichia coli homologue YajL shows both residues may be protonated at the H-bonded oxygen atoms, potentially consistent with a LBHB. A Protein Data Bank-wide screen identifies candidate carboxylic acid H-bonds in approximately 14% of proteins, which are typically short [O–O> = 2.542(2) Å]. Chemically similar H-bonds between hydroxylated residues (Ser/Thr/Tyr) and carboxylates show a trend of lengthening O–O distance with increasing H-bond donor pKa. This trend suggests that conventional electronic effects provide an adequate explanation for short, charge-assisted carboxylic acid–carboxylate H-bonds in proteins, without the need to invoke LBHBs in general. This study demonstrates that bond length analysis of atomic resolution X-ray crystal structures provides a useful experimental test of certain candidate LBHBs.},
doi = {10.1021/acs.biochem.6b00906},
journal = {Biochemistry},
number = 2,
volume = 56,
place = {United States},
year = {Tue Jan 17 00:00:00 EST 2017},
month = {Tue Jan 17 00:00:00 EST 2017}
}
  • Dissociation energies, ..delta..H/sup 0//sub D/, of RO/sup -/ x HOR, RCOO/sup -/ x HOR, and RCOO/sup -/ x HOOCR complexes range from 14 to 29 kcal/mol. Large values of ..delta..H/sup 0//sub D/ are observed for the symmetric dimers CH/sub 3/O/sup -/ x HOCH/sub 3/ (28.8 kcal/mol) and CH/sub 3/COO/sup -/ x HOOCCH/sub 3/ (29.3 kcal/mol). ..delta..H/sup 0//sub D/ decreases as the difference between the acidities of the components increase; e.g., for dimers with large ..delta delta..H/sup 0//sub acid/ such as CH/sub 3/COO/sup -/ x H/sub 2/O and HCOO/sup -/ x H/sub 2/O (..delta delta..H/sup 0//sub acid/ = 42.2 and 45.5more » kcal/mol, respectively), ..delta..H/sup 0//sub D/ = 16.0 kcal/mol. For 13 dimers, a linear correlation of the form ..delta..H/sup 0//sub D/ = 28.4 - 0.29 ..delta delta..H/sup 0//sub acid/ is obtained. Some dimers deviate substantially from the correlation, suggesting special structural effects. For example, the large value of ..delta..H/sup 0//sub D/ = 36.8 kcal/mol for HCOO/sup -/ x HOOCH suggests double hydrogen bonding, involving a CH...O/sup -/ type bond. On the other hand, the data suggest that only one hydrogen bond is formed in RCOO/sup -/ x H/sub 2/O. Comparison between anionic and cationic hydrogen bonded systems shows that the bonding energies are similar for RO/sup -/ x B and ROH/sub 2//sup +/ x B complexes involving the same ligand B, suggesting primarily electrostatic interactions in both, while RCOO/sup -/ x B is weaker by 4-6 kcal/mol than RCOOH/sub 2//sup +/ x B, probably due to charge delocalization in RCOO/sup -/.« less
  • Initial experiments were carried out with nonanoic acid as the model compound with subsequent reactions carried out on decane and branched carboxylic acids. The catalytically deuterated samples, after esterification, were analyzed by mass spectrometry to ascertain the total percent /sup 2/H incorporated and by 2H NMR to determine the site of bond activation. Several transition-metal complexes were studied as catalysts, namely K/sub 2/PtCl/sub 6/, K/sub 2/PtCl/sub 4/, PdCl/sub 2/ and RhCl/sub 3/. Results obtained from /sup 2/H NMR showed that the Pt(II)-catalyzed H--D exchange reaction of nonanoic acid is site selective, favoring the nonpolar end of the molecule. Findings indicatedmore » the reactivity at different kinds of carbon atoms decreases in the order primary > secondary > tertiary. In all instances, with the exception of methyl stearate the greatest extent of deuterium exchange is observed at the primary C--H bond. This study showed the Pt-catalyzed activation of the C--H bonds of saturated carboxylic acid occurs, in general in the same manner as it does in simple alkanes. However, electronic effects play an important role and can influence the selectivity of the reaction. 3 figures, 2 tables.« less
  • A significant increase in the C-O stretching force constant (F{sub CO}) and a decrease in C-O bond length (r{sub CO}) result upon coordination of carbon monoxide to various cationic species. We report a study designed to elucidate the factors responsible for this effect. In particular, we distinguish between an explanation based on electrostatic effects and one based on withdrawal or electron density from the 5{sigma} orbital or CO, an orbital generally considered to have some antibonding character. Ab initio electronic structure calculations on CO in the presence of a positive point charge (located on the carbon side of the bondmore » axis) reveal that a simple Coulombic field increases the C-O stretching force constant and decreases the bond length. Coordination of CO to a simple cationic Lewis acid such as H{sup +} or CH{sub 3}{sup +} is calculated to increase F{sub CO} (and decrease r{sub CO}) to extents slightly less than those engendered by a point charge at the same distance from the carbonyl carbon. These results indicate that electron donation from the 5{sigma} orbital has no intrinsic positive effect on the magnitude of F{sub CO}. Calculations were also conducted on several symmetrical, neutral , and cationic transition metal complexes, including some examples of the recently discovered homoleptic noble-metal carbonyls. 61 refs., 1 fig., 4 tabs.« less
  • The structure of lithium hydrogen phthalate monohydrate has been refined based upon neutron diffraction data obtained at three temperatures: 15, 100, and 298 K. All bond distances have been determined with precision better than 0.002 A. The two crystallographically independent hydrogen phthalate anions in the unit cell both possess very short intramolecular OxxxHxxxO hydrogen bonds with OxxxOroughly-equal2.4 A and angleOxxxHxxxOroughly-equal170/sup 0/. One of these linkages is very decidedly asymmetric, with OxxxH = 1.122(1) A and HxxxO = 1.294(1) A at 15 K, reflecting the fact that the two O atoms have quite different environments in the crystal. The second OxxxHxxxOmore » bond is more nearly symmetric, with OxxxH = 1.195(1) A and HxxxO = 1.205(1) A at 15 K, but the difference between the two distances is still significant. The asymmetry of the short hydrogen bonds appears somewhat more pronounced at 298 K than at the lower temperatures. A corresponding shift with temperature of the H atom in the short intramolecular hydrogen bond was found previously in 2,3-pyridinedicarboxylic acid, which has a molecular geometry similar to that found here.« less