Quantum molecular study of the alkylating agent mechlorethamine

Broch, Henri; Viani, R.; Vasilescu, D.

doi:10.1002/qua.560400715

Cited by 9 publications

(8 citation statements)

References 5 publications

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“…In previous works, we investigated the quantum chemical properties of various forms of HN2 and HD: neutral, aziridinium or episulfonium, free carbonium [ 18,193, and S-methylated forms of sulfur mustard [20] by ab initio computations at the levels 6-31G and 6-31G*. We have also simulated the interaction of HD+ episulfonium and HN2+ aziridinium with an isolated guanine [211.…”

Section: 00mentioning

confidence: 99%

Ab initio modeling of the interaction between guanine?cytosine base pair and mustard alkylating agents

Broch

Hamza

Vasilescu

1996

Int. J. Quantum Chem.

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mInteraction between the guanine-cytosine base pair and the episulfonium form of sulfur mustard (HDf) or the aziridinium form of nitrogen mustard (HN2+) was studied using the ab initio LCAO-MO method at the HF/6-31G level. The alkylation mechanism on the guanine N7 was analyzed by using a supermolecular modeling. Our stereostructural results associated with the molecular electrostatic potentials and highest occupied/lowest unoccupied molecular orbital (HOMO-LUMO) properties show that in vacuum the alkylation of the N7 of guanine by HDt in the agressive episulfonium form is a direct process without a transition state and of which the pathway is determined. Our study shows that interaction of guanine with the aziridinium form of HN2+ necessitates a transition state for the N7 alkylation route. When the N7 guanine alkylation by HD+ or HN2' is achieved, about half of a positive charge moves from the alkylator toward the guanine in both cases. 0 1996 John Wiley & Sons, Inc.

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Section: 00mentioning

confidence: 99%

Ab initio modeling of the interaction between guanine?cytosine base pair and mustard alkylating agents

Broch

Hamza

Vasilescu

1996

Int. J. Quantum Chem.

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“…The different steps of the mechlorethamine molecule alkylation with the guanine have been widely discussed at the previous art [1,2,[8][9][10][11]29,30]. It is know that this molecule reacts with aintramolecular cyclization SN 1 releasing a chloride ion, forming the aziridinium ion.…”

Section: Construction Of the Mechlorethamine Molecule In Different Stmentioning

confidence: 99%

“…The mustard nitrogen compounds are among the most popular agents studied [2,[8][9][10][11] by the theoretical computational chemistry. These compounds form the aziridinium ion, being this ion highly reactive through the intramolecular cyclization SN 1 .…”

Section: Introductionmentioning

confidence: 99%

Computational Study of the Alkylation Reaction of the Nitrogen Mustard Mechlorethamine Using NBO Model and the QTAIM Theory

Almeida¹,

Faria²

2013

OJPC

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Substances known as nitrogen mustards turn into aziridinium ion through the intramolecular cyclization SN 1. This ion reacts with the DNA preferably at the N 7 position of the guanine, and because of this, it is an important antineoplastic agent. Based on this, the objective of this study is to quantify the interaction between the nitrogen mustard mechlorethamine and the guanine, using the NBO analysis and the QTAIM theory. The results of the NBO analysis showed that when the triangular cycle C 4-N 1-C 5 is formed, there is some resonance among these atoms. This analysis also showed that the electronic transition at the sigma antibondingorbital σ* N 1-C 4 presents higher perturbation energy of second order, indicating that this bond is broken at the nucleophilic attack of the N 7 nitrogen of guanine. The analysis that refers to the electron density obtained by the QTAIM theory indicates that the guanine proximity enables an electron density polarization of the BCPs aziridinium ion of mechlorethamine making that the frontal part of the ion becomes electron deficient. Finally, the relative results to the Laplacian of the electron density obtained by the QTAIM theory showed that the guanine approximation increases the "hole" factor at the C 4 , proving that the nucleophilic attack based on the "lump-hole" concept causes the region of that atom is the site of alkylation reaction.

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“…forms [9]. The aim of this article is to present the results obtained for the geometries, the conformations, and the charge distributions of HD in its various forms and to compare the similarities and the differences of these two fundamental molecules belonging to the mustard family.…”

Section: -J 'mentioning

confidence: 99%

“…The HN2+, in quaternized aziridinium ion form, and the HD', in ethylene sulfonium ion form, are the most stable ones in each case, compared to their free carbonium forms. Charge environment of sulfur compared to nitrogen for neutral, strained ring, and free carbonium forms of mustards (minimal energy conformations): (a) sulfur mustard; (b) nitrogen mustard[9].…”

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confidence: 99%

Quantum molecular study of sulfur mustard

Broch

Viani

Vasilescu

1992

Int J of Quantum Chemistry

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The sulfur mustard, HD, a chemical warfare agent, has been studied by ab initio quantum molecular computations (~~/ 6 -3 1 6 * and 6-316) on its various forms (neutral, ethylene sulfonium, and free carbonium ions). The geometries of these molecules have been completely optimized and the minimal energy conformations determined with their associated charge distributions. We discuss these results on electrostatic properties with respect to the mechanism of DNA alkylation by HD and compare them with our previous study of the nitrogen mustard mechlorethamine.

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Quantum molecular study of the alkylating agent mechlorethamine

Cited by 9 publications

References 5 publications

Ab initio modeling of the interaction between guanine?cytosine base pair and mustard alkylating agents

Ab initio modeling of the interaction between guanine?cytosine base pair and mustard alkylating agents

Computational Study of the Alkylation Reaction of the Nitrogen Mustard Mechlorethamine Using NBO Model and the QTAIM Theory

Quantum molecular study of sulfur mustard

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