Intramolecular dihydrogen bond: A new perspective in Lewis acid catalyzed nucleophilic epoxide ring opening reaction

Dixit, Vaibhav A.; Rathi, Prakash Chandra; Bharatam, Prasad V.

doi:10.1016/j.theochem.2010.09.020

Cited by 6 publications

(2 citation statements)

References 34 publications

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“…Ring opening of epoxides has been a subject of interest to experimental and theoretical chemists. ,− Ethylene oxide or oxirane is a three-membered oxygen-containing ring, which is highly strained, electrophilic, and easily undergoes ring opening. The epoxide ring opening reactions of furan epoxide using model nucleophilies and water leading to covalent adduct formation was studied by Taxak and Bharatam using quantum chemical methods .…”

Section: Quantum Chemical Analysismentioning

confidence: 99%

Toxicity Originating from Thiophene Containing Drugs: Exploring the Mechanism using Quantum Chemical Methods

Jaladanki

Taxak

Varikoti

et al. 2015

Chem. Res. Toxicol.

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Drug metabolism of thiophene containing substrates by cytochrome P450s (CYP450) leads to toxic side effects, for example, nephrotoxicity (suprofen, ticlopidine), hepatotoxicity (tienilic acid), thrombotic thrombocytopenic purpura (clopidogrel), and aplastic anemia (ticlopidine). The origin of toxicity in these cases has been attributed to two different CYP450 mediated metabolic reactions: S-oxidation and epoxidation. In this work, the molecular level details of the bioinorganic chemistry associated with the generation of these competitive reactions are reported. Density functional theory was utilized (i) to explore the molecular mechanism for S-oxidation and epoxidation using the radical cationic center Cpd I [(iron(IV)-oxo-heme porphine system with SH(-) as the axial ligand, to mimic CYP450s] as the model oxidant, (ii) to establish the 3D structures of the reactants, transition states, and products on both the metabolic pathways, and (iii) to examine the potential energy (PE) profile for both the pathways to determine the energetically preferred toxic metabolite formation. The energy barrier required for S-oxidation was observed to be 14.75 kcal/mol as compared to that of the epoxidation reaction (13.23 kcal/mol) on the doublet PE surface of Cpd I. The formation of the epoxide metabolite was found to be highly exothermic (-23.24 kcal/mol), as compared to S-oxidation (-8.08 kcal/mol). Hence, on a relative scale the epoxidation process was observed to be thermodynamically and kinetically more favorable. The energy profiles associated with the reactions of the S-oxide and epoxide toxic metabolites were also explored. This study helps in understanding the CYP450-catalyzed toxic reactions of drugs containing the thiophene ring at the atomic level.

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Section: Quantum Chemical Analysismentioning

confidence: 99%

Toxicity Originating from Thiophene Containing Drugs: Exploring the Mechanism using Quantum Chemical Methods

Jaladanki

Taxak

Varikoti

et al. 2015

Chem. Res. Toxicol.

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“…50 A novel reaction eliminating H 2 , rather than the ring-opening reaction, occurs when BH 3 is used as the catalyst.…”

Section: Reactions Of Cyclic Ethersmentioning

confidence: 99%

Nucleophilic Aliphatic Substitution

Westaway¹

2014

Organic Reaction Mechanisms Series

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Heteroatom Effects on Electronic Excited State Hydrogen Bonding of Fluorenone‐Based Molecular Materials

Cheng

Zhang

Zhang³

2013

Heteroatom Chemistry

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In this work, the geometry optimizations in the ground state and electronic excitation energies and corresponding oscillation strengths of the low‐lying electronically excited states for the isolated fluorenone (FN) and FN‐based molecular monomers, the relatively hydrogen‐bonded dimers, and doubly hydrogen‐bonded trimers, are calculated by the density functional theory and time‐dependent density functional theory methods, respectively. We find the intermolecular hydrogen bond CO···HO is strengthened in some of the electronically excited states of the hydrogen‐bonded dimers and doubly hydrogen‐bonded trimers, because the excitation energy in a related excited state decrease and electronic spectral redshift are induced. Similarly, the hydrogen bond CO···HO is weakened in other excited states. On this basis, owing to the important difference of electronegativity, heteroatoms S, Se, and Te that substitute for the O atom in the carbonyl group of the FN molecule have a significant effect on the strength of the hydrogen bond and the spectral shift. It is observed that the hydrogen bond CTe···HO is too weak to be formed. When the CS and CSe substitute for CO, the strength of the hydrogen bonds and electronic spectra frequency shift are significantly changed in the electronic excited state due to the electron transition type transformation from the ππ* feature to σπ* feature. © 2013 Wiley Periodicals, Inc. Heteroatom Chem 24:153–162, 2013; View this article online at http://wileyonlinelibrary.com. DOI 10.1002/hc.21075

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Intramolecular dihydrogen bond: A new perspective in Lewis acid catalyzed nucleophilic epoxide ring opening reaction

Cited by 6 publications

References 34 publications

Toxicity Originating from Thiophene Containing Drugs: Exploring the Mechanism using Quantum Chemical Methods

Toxicity Originating from Thiophene Containing Drugs: Exploring the Mechanism using Quantum Chemical Methods

Nucleophilic Aliphatic Substitution

Heteroatom Effects on Electronic Excited State Hydrogen Bonding of Fluorenone‐Based Molecular Materials

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