Molecular structure and gas-phase reactivity of zileuton and its N-dehydroxylated metabolite: two-layered ONIOM calculations

Remko, Milan; Lyne, Paul; Richards, W. Graham

doi:10.1039/b001064m

Cited by 13 publications

(10 citation statements)

References 31 publications

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“…It has been shown 19,20,[31][32][33][34] that the integrated MO approach, ONIOM, provides an ideal method for accurate calculations for large systems, for such molecules accurate calculations are often too expensive and out of reach. The proton affinity, acidity values, and tautomeric equilibria computed using density functional theory [35][36][37][38][39][40] are as effective as high-level ab initio results and are in good agreement with the corresponding experimental data.…”

Section: E(oniom2) ) E(highmodelmentioning

confidence: 72%

Theoretical Study of Molecular Structure, Tautomerism, and Geometrical Isomerism of Moxonidine: Two-Layered ONIOM Calculations

2001

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The geometries of various tautomers and rotamers of moxonidine in both anionic and protonated forms were optimized using the two-layered ONIOM(B3LYP 6-311+G(d,p): AM1) method. The calculations showed that, in agreement with experiments, moxonidine exists in a more stable imino tautomer. The tautomer containing the amino group is less stable by about 19 kJ/mol. The computed stable conformation for the moxonidine species is characterized by the pyrimidine and imidazolidine rings being in the mutual gauche conformation to one another. In contrast to the parent neutral molecule of moxonidine, ionization caused considerable geometric changes in the anions compared to the neutral species. In the neutral form and anion of the parent drug, an intramolecular hydrogen bond stabilizes the structure and makes the most stable conformations more planar. The primary protonation site is the imidazolidine part of drug. The proton affinity of moxonidine was computed to be −1004 kJ/mol. The moxonidine base was found to be less lipophilic than the base of parent clonidine.

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Section: E(oniom2) ) E(highmodelmentioning

confidence: 72%

Theoretical Study of Molecular Structure, Tautomerism, and Geometrical Isomerism of Moxonidine: Two-Layered ONIOM Calculations

2001

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“…2. It has been shown [27][28][29][30][31][32] that the integrated MO approach, ONIOM, provides an ideal method for the accurate calculations of large systems. For such molecules accurate calculations are often too expensive and out of reach.…”

Section: Methodsmentioning

confidence: 99%

Theoretical Study of Gas-Phase Acidities of Selected Angiotensin-Converting Enzyme Inhibitors

2005

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The structure and gas-phase acidities of six members of large angiotensin-converting enzyme (ACE) inhibitor family [cilazaprilat, silanediol, fosinoprilat, AcSDKP, angiotensin I (terminal part), and RXP 407] have been studied using the ONIOM Becke3LYP/6-311+G(d,p):HF/3-21G * method. The investigated ACE inhibitors are weak acids with calculated acidity of about 1270-1650 kJ mol −1 . Of acids studied the highest gas-phase acidity (1273 kJ mol −1 ) possesses experimental ACE inhibitor RXP 407. This drug, according to the computed pK a value (3.2), is also in water solution the most acidic compound of the ACE inhibitors investigated.

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“…It has been shown [7,48,[60][61][62][63][64] that the integrated MO approach, ONIOM, provides an ideal method for the accurate calculations of large systems. For such molecules, accurate calculations are often too expensive and out of reach.…”

Section: Computational Detailsmentioning

confidence: 99%

Thermodynamics of binding of angiotensin-converting enzyme inhibitors to enzyme active site model

Šramko

Garaj

Remko

2008

Journal of Molecular Structure: THEOCHEM

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Molecular structure and gas-phase reactivity of zileuton and its N-dehydroxylated metabolite: two-layered ONIOM calculations

Cited by 13 publications

References 31 publications

Theoretical Study of Molecular Structure, Tautomerism, and Geometrical Isomerism of Moxonidine: Two-Layered ONIOM Calculations

Theoretical Study of Molecular Structure, Tautomerism, and Geometrical Isomerism of Moxonidine: Two-Layered ONIOM Calculations

Theoretical Study of Gas-Phase Acidities of Selected Angiotensin-Converting Enzyme Inhibitors

Thermodynamics of binding of angiotensin-converting enzyme inhibitors to enzyme active site model

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