Density functional theory calculations of δ(13C) and δ(1H) chemical shifts and 3J(13COO1H) coupling constants as structural and analytical tools in hydroperoxides: Prospects and limitations of 1H13C heteronuclear multiple bond correlation experiments

Ahmed, Raheel; Siskos, Michael G.; Siddiqui, Hamid Latif; Gerothanassis, Ioannis P.

doi:10.1002/mrc.5298

Cited by 7 publications

(5 citation statements)

References 61 publications

(136 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Further NMR and computational studies are currently in progress to investigate the interactions of synthetic analogues of the free fatty acids [12,50] and primary and secondary oxidations products of FFAs [51][52][53] with HSA.…”

Section: Discussionmentioning

confidence: 99%

Molecular Basis for the Selectivity of DHA and EPA in Sudlow’s Drug Binding Sites in Human Serum Albumin with the Combined Use of NMR and Docking Calculations

et al. 2023

Self Cite

View full text Add to dashboard Cite

Medium- and long-chain saturated and unsaturated free fatty acids (FFAs) are known to bind to human serum albumin (HSA), the main plasma carrier protein. Atomic-level structural data regarding the binding mode in Sudlow’s sites I (FA7) and II (FA4, FA3) of the polyunsaturated ω-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), however, are largely unknown. Herein, we report the combined use of saturation transfer difference (STD) and Interligand NOEs for Pharmacophore Mapping (INPHARMA) NMR techniques and molecular docking calculations to investigate the binding mode of DHA and EPA in Sudlow’s sites Ι and ΙΙ of HSA. The docking calculations and the significant number of interligand NOEs between DHA and EPA and the drugs warfarin and ibuprofen, which are stereotypical ligands for Sudlow’s sites I and II, respectively, were interpreted in terms of competitive binding modes and the presence of two orientations of DHA and EPA at the binding sites FA7 and FA4. The exceptional flexibility of the long-chain DHA and EPA and the formation of strongly folded structural motives are the key properties of HSA–PUFA complexes.

show abstract

Section: Discussionmentioning

confidence: 99%

Molecular Basis for the Selectivity of DHA and EPA in Sudlow’s Drug Binding Sites in Human Serum Albumin with the Combined Use of NMR and Docking Calculations

et al. 2023

Self Cite

View full text Add to dashboard Cite

show abstract

“…The significant conformational flexibility of FFAs was also considered to be the main reason that their location in the binding site FA7 in the human serum albumin could not be determined accurately [ 18 , 19 , 64 ] in the available X-ray structural data [ 65 , 66 , 67 ]. The structures of free fatty acids and their oxidation products [ 53 , 54 ], in various solvents with varying hydrogen bond and solvation abilities, are currently under investigation with the combined use of NMR and DFT studies.…”

Section: Discussionmentioning

confidence: 99%

“…The recovery delay was set to 200 μs, and the shaped pulse was set to 50 ms [ 28 ]. NMR experiments were performed on freshly prepared solutions to avoid the formation of significant amounts of primary and secondary oxidation products [ 53 , 54 ].…”

Section: Methodsmentioning

confidence: 99%

Structural Studies of Monounsaturated and ω-3 Polyunsaturated Free Fatty Acids in Solution with the Combined Use οf NMR and DFT Calculations—Comparison with the Liquid State

Venianakis,

Siskos,

Papamokos

et al. 2023

Molecules

Self Cite

View full text Add to dashboard Cite

Molecular structures, in chloroform and DMSO solution, of the free fatty acids (FFAs) caproleic acid, oleic acid, α-linolenic acid, eicosapentanoic acid (EPA) and docosahexaenoic acid (DHA) are reported with the combined use of NMR and DFT calculations. Variable temperature and concentration chemical shifts of the COOH protons, transient 1D NOE experiments and DFT calculations demonstrate the major contribution of low molecular weight aggregates of dimerized fatty acids through intermolecular hydrogen bond interactions of the carboxylic groups, with parallel and antiparallel interdigitated structures even at the low concentration of 20 mM in CDCl3. For the dimeric DHA, a structural model of an intermolecular hydrogen bond through carboxylic groups and an intermolecular hydrogen bond between the carboxylic group of one molecule and the ω-3 double bond of a second molecule is shown to play a role. In DMSO-d6 solution, NMR and DFT studies show that the carboxylic groups form strong intermolecular hydrogen bond interactions with a single discrete solvation molecule of DMSO. These solvation species form parallel and antiparallel interdigitated structures of low molecular weight, as in chloroform solution. This structural motif, therefore, is an intrinsic property of the FFAs, which is not strongly affected by the length and degree of unsaturation of the chain and the hydrogen bond ability of the solvent.

show abstract

“…The recovery delay was set to 200 µs, and the shaped pulse was set to 50 ms [28]. NMR experiments were performed on freshly prepared solutions to avoid the formation of significant amounts of primary and secondary oxidation products [53,54].…”

Section: Chemicals and Reagentsmentioning

confidence: 99%

Structural Studies of Monounsaturated and ω-3 Polyunsaturated Free Fatty Acids in Solution with the Combined Use οf NMR and DFT calculations -Comparison with the Liquid State

Gerothanassis¹,

Siskos²,

Papamokos³

et al. 2023

Preprint

View full text Add to dashboard Cite

Molecular structures, in chloroform and DMSO solution, of the monounsaturated free fatty acids (FFAs) caproleic acid (dec-9-enoic acid) and oleic acid (octadec-9-enoic acid) and the ω-3 FFAs α-linolenic acid (9Z,12Z,15Z)-octadeca-9,12,15-trienoic acid ALA), eicosapentanoic acid (5Z,8Z,11Z,14Z,17Z)-icosa-5,8,11,14,17-pentaenoic acid) and docosahexaenoic acid (4Z,7Z,10Z,13Z,16Z,19Z)-docosa-4,7,10,13,16,19-hexaenoic acid), are reported with the combined use of NMR and DFT calculations. Variable temperature and concentration chemical shifts of the COOH protons and transient 1D NOE experiments, in CDCl3, demonstrate the major contribution of low molecular weight aggregates of dimerized fatty acids, through intermolecular hydrogen bond interactions of the carboxylic groups, with parallel and antiparallel interdigitated structures, even at the low concentration of 20 mM. For the dimeric DHA, a structural model of an intermolecular hydrogen bond through carboxylic groups and an intermolecular hydrogen bond between the carboxylic group of one molecule and the ω-3 double bond of a second molecule, is shown to play a role. In DMSO-d6 solution the centro-symmetric hydrogen bond interactions are broken and the carboxylic groups form strong intermolecular hydrogen bond interactions with a discrete solvation molecule of DMSO. These solvation species form parallel and antiparallel interdigitated structures of low molecular weight. DFT structural models in CHCl3 and DMSO, in agreement with the NMR data, are compared with the structures in the liquid state

show abstract

Density functional theory calculations of δ(¹³C) and δ(¹H) chemical shifts and ³J(¹³COO¹H) coupling constants as structural and analytical tools in hydroperoxides: Prospects and limitations of ¹H¹³C heteronuclear multiple bond correlation experiments

Cited by 7 publications

References 61 publications

Molecular Basis for the Selectivity of DHA and EPA in Sudlow’s Drug Binding Sites in Human Serum Albumin with the Combined Use of NMR and Docking Calculations

Molecular Basis for the Selectivity of DHA and EPA in Sudlow’s Drug Binding Sites in Human Serum Albumin with the Combined Use of NMR and Docking Calculations

Structural Studies of Monounsaturated and ω-3 Polyunsaturated Free Fatty Acids in Solution with the Combined Use οf NMR and DFT Calculations—Comparison with the Liquid State

Structural Studies of Monounsaturated and ω-3 Polyunsaturated Free Fatty Acids in Solution with the Combined Use οf NMR and DFT calculations -Comparison with the Liquid State

Contact Info

Product

Resources

About