Bahoueddine Tangour

Encapsulation into Carbon Nanotubes and Release of Anticancer Cisplatin Drug Molecule

Molecular dynamics simulations have been investigated to study the interactions between single-wall carbon nanotubes and an anticancer agent Pt complex (Cisplatin). The optimized diameter of the vector system has been determined to encapsulate in the best conditions the drug molecules. The simulation results show also that several drug molecules can be adsorbed inside the nanotubes, leading to an increased confinement time. Moreover, our simulations show that the release of the drug near a cell membrane model is favored, opening the way to a natural drug nanocapsule.

Water and hydroxide ion pathways in the σ-complexation of superelectrophilic 2-aryl-4,6-dinitrobenzotriazole 1-oxides in aqueous solution. A kinetic and thermodynamic study

As part of our continuing studies of the highly electron-deficient nature of nitrobenzofuroxans, nitrobenzofurazans and related heterocycles, we report here a kinetic and thermodynamic study of σ-complexation for a series of 2-aryl-4,6 -dinitrobenzotriazole 1-oxides (3a–e) over a large pH range in aqueous solution. The reaction series represents a modulation in electrophilic properties of the benzotriazole moiety in formation of the corresponding hydroxy σ-adducts (4a–e). Analysis of the data has allowed dissection of observed rates into forward (kH2O1, kOH−2) and reverse (kH+−1, k−2) rate constants as well as the obtention of pKa values for H2O addition to the benzotriazole moiety. Our results reveal that 3a–e are superelectrophilic compounds with respect to 1,3,5-trinitrobenzene (TNB) as a standard electron-deficient aromatic, but less superelectrophilic compared to 4,6-dinitrobenzofuroxan (DNBF). Some data pertaining to buffer catalysis of the formation and decomposition of the adducts together with solvent deuterium isotope effects for these pathways are also reported. From these results, it is concluded that adduct formation occurs via general base catalyzed water attack: the general bases include notably H2O, HCO3−, CO32− as well as OH−. This contrasts with the situation for the σ-complexation of DNBF where HCO3− nand CO32− were found to act as nucleophilic catalysts whereas OH− functioned as a general base catalyst. This contrasting behaviour provides further evidence that the dinitro-activated carbocyclic ring of the benzotriazoles 3a–e ranks somewhat lower in electrophilic/superelectrophilic properties compared to that in DNBF. Altogether, the results provide a basis for understanding the relationship between the superelectrophilic reactivities, as evidenced by the contrasting kinetic and thermodynamic properties of the systems at hand, and the varied abilities of these substrates to react in pericyclic Diels–Alder reactions.

A density functional theory study of dinitrogen bonding in ruthenium complexes

Abstract Dinitrogen ruthenium complexes were theoretically studied by means of DFT technique. Several isomers of RuH 2 (N 2 )(PH 3 ) 2 , RuH 2 (N 2 ) 2 (PH 3 ) 2 and RuH 2 (H 2 )(N 2 )(PH 3 ) 2 were studied. Calculations of relative energies, geometrical parameters, vibrational frequencies and natural orbital bond analysis were performed. It is shown that the most stable isomer for each series is characterized by a trans position of the phosphines with the dinitrogen ligand trans to one hydride. As usually observed, the dinitrogen moiety adopts an end-on bonding mode and is weakly elongated from free N 2 (generally not >1%). As shown by NBO analysis, such a bonding mode involves σ-donation of about 0.2 electron from the lone pair orbital of the ruthenium-bound nitrogen toward ruthenium and back-donation of roughly 0.2 electron from the 4d occupied orbital of ruthenium to the two π g * dinitrogen orbitals.

A DFT study of germane activation in ruthenium complexes. σ-coordination versus oxidative addition

The coordination of GeH4 to the ruthenium complex RuH2(η2-H2)2(PH3)2 can lead to oxidative addition or σ-bond coordination of the germane. The corresponding germyl or σ-isomers have been optimized by DFT using the B3LYP hybrid functional. The most stable isomer corresponds to a germyl bis(dihydrogen) complex RuH(GeH3)(η2-H2)2(PH3)2 n(1T-b1) with trans phosphines. It is only 2 kcal mol−1 below the σ-isomer RuH2(η2-H2)(η2-H–GeH3)(PH3)2 n(1C-a1). This is in contrast to what has been previously observed in the corresponding silane chemistry, in which σ-coordination was favoured. However, calculated binding energies for GeH4 or SiH4 to the RuH2(H2)(PH3)2 fragment are very similar (−21.3 and −22.2 kcal mol−1, respectively). The nature of the metal–germane interaction is analysed by natural bond orbital (NBO) calculations.

The Cytochrome P450 3A4 has three Major Conformations: New Clues to Drug Recognition by this Promiscuous Enzyme

We computed the channels of the 3A4 isoform of the cytochrome P450 3A4 (CYP) on the basis of 24 crystal structures extracted from the Protein Data Bank (PDB). We identified three major conformations (denoted C, O1 and O2) using an enhanced version of the CCCPP software that we developed for the present work, while only two conformations (C and O2) are considered in the literature. We established the flowchart of definition of these three conformations in function of the structural and physicochemical parameters of the ligand. The channels are characterized with qualitative and quantitative parameters, and not only with their surrounding secondary structures as it is usually done in the literature

Controlling activation barrier by carbon nanotubes as nano-chemical reactors

The oxidative addition of primary amine on a monocyclic phospholane was studied in confined conditions. This one-step chemical reaction has been investigated using the DFT technique to elucidate the role of confinement in carbon nanotubes on the reaction. Calculations were carried out by a progressive increase of the nanotube diameters from 10xa0Å to 15xa0Å in order to highlight the dependence of the reactivity on the nanotube diameter. First, single point investigations were dedicated to the study of reactants, transition states, and products placed in the different nanotubes while keeping their optimized structure as free compounds. Second, all studied compounds were relaxed inside nanotubes and their geometries were fully optimized. Within these approaches, we proved that the activation barrier could be controlled depending on the confinement, generating a well-controlled catalysis process.

Theoretical and experimental reinvestigation of methoxide ion reaction with 7-methyl 4-nitro benzofuroxan

DFT/B3LYP theoretical study has been performed in order to interpret the kinetic-thermodynamic competition between compounds obtained by reaction of the methoxide ion on the 7-methyl 4-nitro benzofuroxan. Geometry, atomic charge distribution, transition states, IRC path, thermodynamic, and kinetic parameters (ΔrHT∘, ΔrST∘, ΔrGT∘, ΔH*, ΔS*, and ΔG*) have been calculated for all possible products. In gaseous state or in the presence of water as solvent, all ΔrGT∘ values were found to be negative, ranging from −12.54kcal mol−1 to −29.85kcal mol−1 in water, indicating that all possible products should form spontaneously. Those values indicated the possible observation of all products but experimenters only detect simultaneously two σ-complexes in C5 and C7 among three possibilities. The Fukui indices obtained by NBO atomic charge distribution confirm the super electrophilicity of those two sites. For transition states barriers, ΔG* ranged from 18.98kcal mol−1 to 42.12kcal mol−1 in gaseous state and from 18.59kcal mol−1 to 24.22kcal mol−1 in water. The unexpected result of our calculations is that the most stable compound is the unobserved carbanion but it also exhibits the highest activation barrier. Our results indicated the existence of two consecutive kinetic/thermodynamic competitions that occur in separate periods. The simultaneous observation of the three compounds is impossible because compound 4 occurs as a trace at the time compound 2 disappears completely. Experimental reinvestigation of the studied reaction leads by a very slow process to the earlier unobserved carbanion. Reaction mechanisms were also discussed on the basis of IRC calculations.

In silico study of spacer arm length influence on drug vectorization by fullerene C 60

This work studies theoretically the effect of spacer arm lengths on the characteristics of a fullerene C60-based nanovector. The spacer armis constituted of a carbon chain including a variable number of methylene groups (n = 2-11). To improve the ability of the fullerene carriage, two arms are presented simultaneously through amalonyl bridge. Then the evolution of selected physicochemical parameters is monitored as a function of the spacer arm length and the angle between the two arms. We show here that while the studied characteristics are almost independent of the spacer arm length or vary monotonically with it, the dipole moment and its orientation vary periodically with the parity of the number of carbon atoms. This periodicity is related to both modules and orientations of dipole moments of the spacer arms. In the field of chemical synthesis, these results highlight the importance of theoretical calculations for the optimization of operating conditions. In the field of drug discovery, they show that theoretical calculations of the chemical properties of a drug candidate can help predict its in vivo behaviour, notably its bioavailability and biodistribution, which are known to be tightly dependent of its polarity.

Theoretical ab initio study of NO and CO depollution reaction catalyzed by zinc

Abstract The reaction between NO and CO leading to N2 and CO2 is the most studied depollution process of the former molecules. Ab initio study of a multi-stage mechanism of this reaction catalyzed by zinc was performed at SCF level. Many intermediates, such as ZnCO, ZnNO, ZnO and NCO, intervene in the proposed mechanism. Geometrical parameters, atomic charge, dipole moment and vibrational normal mode wave numbers of intervening molecules were calculated. Thermochemistry parameters (ΔH, ΔG, ΔS) were also obtained. Transition state has been determined and has also allowed us to discuss the reaction mechanism.

Interaction of HF, HBr, HCl and HI molecules with carbon nanotubes

The present work applies the density functional theory (DFT) to study the interactions between armchair (n,n) single walled carbon nanotubes (SWCNTs) and hydrogen halides confined along the nanotube axis and perpendicular to it. Calculations are performed using the CAM-B3LYP functional. According to the hydrogen halides orientation and the internal diameter of CNTs hollow space, HF, HCl, HBr and HI behave differently. The nanoconfinement alters the charge distribution and the dipolar moment. The encapsulated hydrogen fluoride (HF) molecule is stable along and perpendicular to the nanotubes (5,5) and (6,6) axis. The hydrogen chloride (HCl), hydrogen bromide (HBr) and hydrogen iodide (HI) form stable systems inside the nanotube (6,6) only at the perpendicular orientation. In addition, other phenomena are observed such as leaving the nanotube or decreasing the bond length of the molecule and even the creation of covalent bind between the guest molecule and the host nanotube.