Conformational analysis: A new approach by means of chemometrics

Bruni, Aline Thais; Leite, Vitor Barbanti Pereira; Ferreira, Márcia M. C.

doi:10.1002/jcc.10004

Cited by 15 publications

(16 citation statements)

References 37 publications

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“…However, it is sometimes impossible to use this method, due to the enormous combinatorial complexity of the problem. Targeting to handle this problem, the methodology where systematic search is coupled to Principal Component Analysis (PCA) was used to carry out the conformational analysis of omeprazole 12. In this approach, the potential energy surfaces (PES) were obtained for pairs of angles with free rotation, aiming the decrease of the dimensional space.…”

Section: Methodsmentioning

confidence: 99%

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Theoretical study of omeprazole behavior: Racemization barrier and decomposition reaction

Bruni

Ferreira

2008

Int J of Quantum Chemistry

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Omeprazole is a substituted benzimidazole which suppresses gastric-acid secretion by means of H ϩ , K ϩ -ATPase inhibition. It is an optically active drug with the sulfur of the sulfoxide being the chiral center. This pro-drug can be easily converted into its respective sulfenamide at low pH. In this work, omeprazole has been studied in relation to racemization barrier and decomposition reaction. Quantum chemistry coupled to PCA chemometric method were used to find all minimum energy structures. Conformational analysis and calculation of racemization barriers were carried out by PM3 semiempirical method (Gaussian 98). The average racemization energy barrier for all minimum energy structures (43.56 kcal mol Ϫ1 ) can be related to the velocity constant in Eyring's equation. The enormous half-life time at 100°C (9.04 ϫ 10 4 years) indicates that the process cannot be observed in human time scale. On the other hand, the difference of free energy change (⌬(⌬G) ϭ Ϫ266.78 kcal mol Ϫ1 ) for the decomposition reaction shows that the process is favorable to the sulfenamide formation. The highly negative ⌬(⌬G) obtained for the decomposition reaction shows that this process is extremely exothermic. This result explains why omeprazole decomposes and does not racemize. MethodologyBy observing Figure 1, one can note that there are some bonds with free rotation. Thus, the determination of possible minimum energy structures is very important and must be performed previously FIGURE 3. Omeprazole metabolism. FIGURE 5.Omeprazole-optimized conformations and X-ray structure comparison: (a) superimposed conformation A and X-ray structure; (b) superimposed conformation B and X-ray structure; (c) superimposed conformation C and Xray structure; (d) superimposed conformation D and X-ray structure; and (e) superimposed conformations B and D.

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Section: Methodsmentioning

confidence: 99%

“…PCA was applied on the data set containing the referring potential energy surfaces values obtained in agreement with Eq. (2) 12.…”

Section: Methodsmentioning

confidence: 99%

Theoretical study of omeprazole behavior: Racemization barrier and decomposition reaction

Bruni

Ferreira

2008

Int J of Quantum Chemistry

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“…The new methodology whereby the systematic search is coupled to principal component analysis (PCA) was performed in all cases [32].…”

Section: Methodsmentioning

confidence: 99%

“…The compounds in Figure 2 were submitted firstly to conformational analysis using the semi-empirical PM3 method [30] implemented in the Gaussian 98 program [31]. The new methodology whereby the systematic search is coupled to principal component analysis (PCA) was performed in all cases [32].…”

Section: Methodsmentioning

confidence: 99%

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Omeprazole and analogue compounds: a QSAR study of activity against Helicobacter pylori using theoretical descriptors

Bruni

Ferreira

2002

Journal of Chemometrics

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Omeprazole and analogues were studied with respect to their activity as inhibitors of urease Helicobacter pylori. Conformational analysis was performed according to the method proposed by Bruni et al. Theoretical descriptors were calculated by an ab initio method (6±31G** basis set). Since several minimum energy structures were obtained for each compound, and the calculated descriptors proved to be sensitive to the structural conformation, different criteria were proposed for conformation selection. Three data sets were generated wherein conformations were grouped according to minimum heat of formation, minimum electronic energy and structural similarity. For these three sets, experimental per cent of control was used to develop quantitative structure±activity models by PLS. Their cross-validation and correlation coefficients were very good (Q 2 = 0.97 and R 2 = 0.99 on average) and the standard error of validation was much smaller in comparison with results from the literature.

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Exploring the Influence of the Phosphorus‐Heteroatom Substitution in Nicotine on Its Electronic and Vibrational Spectroscopic Properties

Taherivardanjani,

Wylie,

Dötzer

et al. 2023

Chemistry A European J

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The influence of phosphorus substitution of nitrogen in heterocyclic compounds on the vibrational spectroscopy as well as frontier molecular orbitals are analyzed. Nicotine with two nitrogen atoms in its structure is taken as the sample system to be studied computationally. By replacing the nitrogen atom in one or both rings of this molecule with phosphorus, three nicotine derivatives are created. The vibrational circular dichroism and infrared spectra of these four molecules in their monomer state, as well as the assemblies up to trimers are determined. The aforementioned spectra are calculated using static quantum chemical calculations employing a cluster‐weighted approach. The calculated gas phase spectra of nicotine are compared to their respective experimental spectra. It is observed that the nicotine derivatives with phosphorus in the methylpyrrolidine ring have considerably different gas phase and bulk phase vibrational circular dichroism spectra when compared to nicotine. The phosphorus substitution reduces the energy gap between the highest occupied molecular orbital and the lowest unoccupied molecular orbital as well as altering the polarizability and reactivity of the investigated molecules.

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Conformational analysis: A new approach by means of chemometrics

Cited by 15 publications

References 37 publications

Theoretical study of omeprazole behavior: Racemization barrier and decomposition reaction

Theoretical study of omeprazole behavior: Racemization barrier and decomposition reaction

Omeprazole and analogue compounds: a QSAR study of activity against Helicobacter pylori using theoretical descriptors

Exploring the Influence of the Phosphorus‐Heteroatom Substitution in Nicotine on Its Electronic and Vibrational Spectroscopic Properties

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