Tautomerism in folic acid: Combined molecular modelling and NMR study

Gocheva, Gergana; Petkov, Nikolay; Luri, Andrea; Iliev, Stoyan; Ivanova, Nikoleta; Petrova, Jordanka; Mitrev, Yavor; Madjarova, Galia; Ivanova, Anela

doi:10.1016/j.molliq.2019.111392

Cited by 12 publications

(23 citation statements)

References 35 publications

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“…The neutral PT moiety exists in different tautomeric forms while the anion form has different mesomers [38,50], as reviewed in Appendix A-Supplementary Material (SM). The neutral PT (as in FA and HFol 2ion) exhibits a keto-enol (lactam-lactim) equilibrium between C4=O and N3-H groups (see…”

Section: Resultsmentioning

confidence: 99%

“…It is significantly increased in pH values above 5 [37], for which the dianion (HFol 2-) and trianion (Fol 3-) are then dominant species [2] (Figure 1b). Therefore, folate anionic species which studies are often neglected must nevertheless be considered because of: (i) at physiological pH value for which HFol 2is predominant [38][39][40]; (ii) the preparation of many materials and compounds (or the handle of FA in some studies) are performed at pH values above 5 [7,14,[22][23][24][31][32][33][34]; and (iii) the supramolecules assembled by FA are pH-responsiveness [25][26][27]. Braga et al [41] prepared dianionic folates salts (Li, Na and Ca) and showed their higher dissolution rate as well as higher thermal stability than FA.…”

Section: Introductionmentioning

confidence: 99%

“…However, the experimental and theoretical spectroscopic analyses of folate salt are not accomplished yet. Gocheva et al [38] studied the tautomerism of dianion folate (HFol 2-) in water by 1 H-and 13 C-NMR and interpreted the results based on DFT calculations with the Polarizable Continuum Model (PCM). Experimental and calculated IR spectra of palladium and platinum folate complexes were reported by He et al [24], but the theoretical (DFT) values and the correlated attribution were not presented.…”

Section: Introductionmentioning

confidence: 99%

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Folic acid and sodium folate salts: Thermal behavior and spectroscopic (IR, Raman, and solid-state 13C NMR) characterization

Magri

Rocha

Matos

et al. 2022

Spectrochimica Acta Part A: Molecular and Biomolecular Spectros

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Folic acid and sodium folate salts: Thermal behavior and spectroscopic (IR, Raman, and solid-state 13C NMR) characterization

Magri

Rocha

Matos

et al. 2022

Spectrochimica Acta Part A: Molecular and Biomolecular Spectros

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“…The lactim isomer was reported to be 7.8 kcal/mol less stable than the lactam one. A DFT–NMR combined study was carried out to compare the stability of six tautomers of the dicarboxylate folate dianion . It was shown that the most stable tautomer is the lactam form of Scheme A.…”

Section: Introductionmentioning

confidence: 99%

“…A DFT−NMR combined study was carried out to compare the stability of six tautomers of the dicarboxylate folate dianion. 17 It was shown that the most stable tautomer is the lactam form of Scheme 1A. While the lactim isomer is unfavorable, oxidation was suggested to take place by the isomer (Scheme 2).…”

Section: Introductionmentioning

confidence: 99%

How Is the Oxidation Related to the Tautomerization in Vitamin B9?

2021

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The relationship between the lactim−lactam tautomerization and the free-radical scavenging reaction in vitamin B9 [folic acid (FA)] was investigated by density functional theory calculations. 6-Methylpterin was also adopted for the detailed analyses of various reaction paths. For pterin, the transition state of the tautomerization with two water molecules (n = 2) was calculated to be of the lowest activation energy. The protontransfer circuit of n = 2 is retained (not broken) even with the addition of outer water molecules, n = 2 + 2, 2 + 4, 2 + 8, and 2 + 14. At the oxidation of the system composed of 6-methylpterin + (H 2 O) 2 + HO • , the radical character of HO • is directly transmitted to the pterin ring along with the C−O → H → O → H → O → H → OH proton transfer. The patterns of the electron transfer (pterin ring → OX • ) and the concomitant proton transfer via the water dimer were commonly obtained for the oxidant (OX. The hydrogen atom transfer mechanism was ruled out. Two conformations of the puckered form with the −C(O)−OH•••N intramolecular hydrogen bonds of FA were found to have the stability similar to that of the linear conformer. Both the tautomerization and the oxidation were calculated to occur competitively in the three conformers.

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Advancements and Perspectives in Folate‐Based Anticancer Drugs: Bridging Quantum and Classical Mechanics in Folate Receptor Research

Josiah,

Govender,

Govender

et al. 2024

Advcd Theory and Sims

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This review highlights the role of computational chemistry, specifically quantum and molecular mechanics, in the development of folate‐based anticancer drugs. Folate receptors (FRs) are overexpressed in cancerous cells, rendering these receptors a key focus in the design of targeted drug delivery systems. These computational tools are fundamental for analyzing drug–receptor interactions and overcoming the limitations of traditional drug development processes. A 10‐year literature survey demonstrated advancements in employing FRs for targeted cancer therapy. Key findings reveal that structural modifications to folate derivatives consistently enhance binding affinities and specificity toward FRα and FRβ. Computational methodologies predicted and analyzed molecular interactions, validated by experimental data. Functional groups play a crucial role in enhancing binding stability and interaction strength within FR binding pockets. Detailed structural insights into folate derivatives and antifolates interacting with FRs have identified critical residues involved in binding, aiding the design of targeted therapeutics.

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Tautomerism in folic acid: Combined molecular modelling and NMR study

Cited by 12 publications

References 35 publications

Folic acid and sodium folate salts: Thermal behavior and spectroscopic (IR, Raman, and solid-state 13C NMR) characterization

Folic acid and sodium folate salts: Thermal behavior and spectroscopic (IR, Raman, and solid-state 13C NMR) characterization

How Is the Oxidation Related to the Tautomerization in Vitamin B9?

Advancements and Perspectives in Folate‐Based Anticancer Drugs: Bridging Quantum and Classical Mechanics in Folate Receptor Research

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