Molecular Orbital Descriptors Research Articles

VIBRATIONAL SPECTROSCOPIC STUDY OF PYRIDINE AND PYRIMIDINE LIGANDS COORDINATED WITH ANTIMONY (III) COMPLEXES: INSIGHTS FROM DFT CALCULATIONS

By employing the Scaled Quantum Mechanics Force Field (SQMFF) methodology, a comprehensive analysis was conducted to assign the vibrational spectra of three antimony (III) compounds, [1a-3a], that possess pyridine and pyrimidine ligands. The potential energy distribution (PED) was calculated and utilized to assign the IR spectra of the antimony (III) compounds. The theoretical frontier molecular orbital descriptors, the partial and total density of state distribution (TDOS, PDOS), molecular electronic potential surface map (MEP), nonlinear optical properties (NLO) of these complexes also were computed and investigated. The DFT/B3LYP/GEN (C, H, N, Cl: 6-31G(d,p) and Sb: LanL2DZ) level was utilized for all DFT calculations using the Gaussian 09W program. Furthermore, theoretical frontier molecular orbital descriptors, including electronegativity, chemical potential, softness, electrophilicity index, and electron affinity for six antimony (III) compounds were calculated ([1a/1b-3a/3b]). The results showed that, the ionization potential energy value of the [3a], which had the lowest experimental Leishmania activity, was also found to be the lowest among the others.

Tuning the resonance-assisted hydrogen bond (RAHB) of malonaldehyde using π-conjugated substituents and presentation of its energy decomposition

Position of substituents (R1 = H and R2, R3 = H, F, CnHn+1) on malonaldehyde has been changed to amplify its intramolecular hydrogen bonding (IHB) interaction. Results show that π-conjugated substituents at R3 position cause increase of IHB energies of the substituted malonaldehydes. Then, amplification of the IHB interaction in malonaldehyde with C20H21 group at R3 position was verified. Thus, polyethylene chains influence on resonance-assisted hydrogen bond (RAHB) of malonaldehyde and can form malonaldehyde-polyene materials with improved properties. Then, hydrogen bond (HB) interaction of formaldehyde with the substituted malonaldehydes without RAHB ring was studied and HB interaction energies calculated. The HB interaction energies have linear relation with intermolecular hydrogen bond length (dHB). A procedure was employed to estimate IHB energies of the substituted malonaldehydes using the mentioned relation and intramolecular hydrogen bond length (dIHB). Relation between geometrical parameters, spectroscopic data, topological properties, and molecular orbital descriptors with the estimated IHB energies were surveyed. Moreover, IHB energies of the current system were estimated using some quantum chemistry methods to validate the data and find more consistent method with the proposed viewpoint. Results indicated that the estimated IHB energies using proposed procedure have good correlations with other methods. Also, energy decomposition of the IHB interactions in the substituted malonaldehydes was performed using a new method and results showed that electrostatic term has major contribution in the IHB energies.

Seeking the Optimal Descriptor for SN2 Reactions through Statistical Analysis of Density Functional Theory Results.

Bimolecular nucleophilic substitution is one of the fundamental reactions in organic chemistry, yet there is still knowledge to be gained on the role of the nucleophile and the substrate. A statistical treatment of over 600 density functional theory (DFT)-computed barriers for bimolecular nucleophilic substitution at methyl derivatives (SN2@C) leads to the identification of numerical descriptors that best represent the entering and leaving ability of 26 different nucleophiles. The treatment is based on singular value decomposition (SVD) of a matrix of computed energy barriers. The current work represents the extension to a problem of reactivity of the hidden descriptor methodology that we had previously developed for the thermodynamic problem of bond dissociation energies in transition-metal complexes. The analysis of the results shows that a single descriptor is sufficient. This hidden descriptor has different values for nucleophilic and leaving abilities and, contrary to expectation, does not correlate especially well with either frontier molecular orbital descriptors or solvation descriptors. In contrast, it correlates with other thermodynamic and geometric parameters. This statistical procedure can be in principle extended to additional chemical fragments and other reactions.

A comparative study of interplay effects between the cation-π and intramolecular hydrogen bond interactions in the various complexes of methyl salicylate with Mn+, Fe2+, Co+, Ni2+, Cu+, and Zn2+ cations

The interplay among two important noncovalent interactions involving aromatic ring is studied by means of density functional theory (DFT) calculations on complexes of methyl salicylate with Mn+, Fe2+, Co+, Ni2+, Cu+, and Zn2+ cations. The energetic, geometrical, spectroscopic, topological, and molecular orbital descriptors are applied to evaluate the strength of the cation-π and intramolecular hydrogen bond (IMHB) interactions. These outcomes are compared with the parent molecule of methyl salicylate and the corresponding results of benzene (BEN) complexes with the cited cations as a set of reference points. Based on the energetic conclusions, for the double-charge cations, the simultaneous presence of these interactions enhances the strength of the cation-π, while for the mono-charge cations, the reverse process is observed. On the other hand, for both type of the cations (mono- and double-charge), the coupling of noncovalent interactions reduces the strength of the IMHB in the studied systems. The computations in this study are discussed with the Bader theory of atoms in molecules (AIM), the natural bond orbital (NBO) analysis, and the frontier molecular orbital (FMO) theory.

Theoretical study of encapsulation of Floxuridine anticancer drug into BN (9,9-7) nanotube for medical application

Due to the toxicity and resistance of anticancer drugs, various methods have been investigated to improve their effects in cancer treatment. Since boron nitride nanotubes (BNNTs) are biocompatible and nontoxic, they can act as fine drug delivery vehicles of these anticancer drugs to deliver them directly to the target cells. In this research encapsulation of Floxuridine as anticancer drug into the boron nitride nanotube (9,9-7) are investigated using density functional theory (DFT). Analysis of the adsorption energy reveals that the encapsulation process is favorable. Furthermore, the strengths of the bonds of the system are estimated by energetic, geometric and molecular orbital descriptors. Some analyses have been made to explore any change in binding characteristics of the drug molecule after encapsulation to nanotube. The interaction effects of Floxuridine drug and boron nitride nanotube (9,9-7) on the electronic properties, chemical shift tensors and natural charge was also determined and discussed. It is believed that these studies can contribute to the understanding of the interaction between the drug molecule and BNNT and to the development of BNNT-based drug delivery devices.

Ab initio study of aerogen-bonds between some heterocyclic compounds of benzene with the noble gas elements (Ne, Ar, and Kr)

Ab initio calculations have been performed to study the complexes between the noble gas elements (Ae = Ne, Ar, Kr) with a series of benzene isoelectronic heterocyclic compounds of benzene, including boraphosphinine (BP), borazine (BN), and alumazine (AlN), at MP2/Aug-CC-pVTZ level of theory. According to the molecular electrostatic potential (MEP) iso-surface of BP, BN, and AlN, the active sites of rings are identified which utilized to predict the relative strength of aerogen···π (Ae···π) interactions as follows: Kr···π > Ar···π > Ne···π/Ae···BP > Ae···BN > Ae···AlN. Then, the equilibrium structures of all the complexes are characterized, and their energetic, geometrical, topological, and molecular orbital descriptors were used to estimate the strength of Ae···π interactions, that are in line with MEP results. Energy decomposition analysis reveals that dispersion effects play a vital role in formation of the Ae···π complexes. Furthermore, intermolecular interactions were also investigated with the quantum theory of atoms in molecules (QTAIM) and the non-covalent interactions (NCI) and natural bond orbital’s (NBO) analysis. NBO analysis showed that like the benzene complexes, charge transfers from the noble gas atom to heterocyclic ring have occurred. Finally, the aromaticity of the rings is measured using the well-established indices namely the nucleus independent chemical shift (NICS) and the average two-center index (ATI).

Quantum chemical study of the nature of interactions between the boraphosphinine and alumaphosphinine with some of the mono- and divalent cations: cation–π or cation–lone pair?

Quantum chemical study of the nature of interactions between the boraphosphinine (BP) and alumaphosphinine (AlP) with some of the alkali metal cations (Li+, Na+, K+) and alkaline-earth cations (Be2+, Mg2+, Ca2+) have been investigated at M06-2X/6-311++G(d,p) level of theory. At first, the molecular and electronic structures of the rings (R) and cations (M) were completely analyzed. According to the molecular electrostatic potential (MEP) iso-surface of BP and AlP, the active sites of rings are identified and also predict the relative strength of M···R interactions as follows: Be2+···R > Mg2+···R > Ca2+···R > Li+···R > Na+···R > K+···R. Furthermore, all of the complexes are characterized and their energetic components, geometrical, topological, and molecular orbital descriptors were used to estimate the strength of M···R interactions. The result shows that the non-covalent interactions of M···AlP are significantly stronger than the corresponding M···BP ones. Detail investigation of M···BP and M···AlP series clearly shows a substantial difference in the nature of interactions, cation–π/cation–lone pair (LP) in M···BP/M···AlP complexes. The excellent linear correlations between the energy terms and all of the mentioned descriptors are obtained. Finally, two well-established indices namely the nucleus independent chemical shift (NICS) and the average two-center index (ATI) were used to evaluate the aromaticity of the studied rings before and after complexation.

The influence of 5-fluorouracil anticancer drug on the DNA base pairs; a quantum chemical study

In the present study, various hydrogen bonded complexes between five-fluorouracil (FU) with AT and GC base pairs were studied. First, to determine the affinity of different sites of the parent structures (FU, AT, and GC) for the hydrogen bond formation, their molecular electrostatic potentials are explored. The complexation energies and the strength of individual HBs of the plausible complexes were evaluated by energetic, geometric, spectroscopic, topologic, and molecular orbital descriptors. Our results reveal that, the FU–GC complexes (34.76–44.42 kcal mol−1) are more stable than the FU–AT ones (21.00–30.35 kcal mol−1). Among the complexes, the FU3–AT1 and FU3–GC3 are the most stable structures in the both series, which can be related to the sites with the highest affinity. Second, a detail analysis of the hydrogen bond descriptors were performed to elucidate the effect of FU on the strength of HB interactions within the base pairs. Interestingly, due to the formation of various interactions between the active sites of basic molecules, the strength of HB within the base pairs in the most cases increase about +2.75 and +.57 kcal mol−1 for the GC and AT nucleobases, respectively. Finally, several aromatic indices (HOMA, FLU, NICS (0) and NICS (1)) were applied to evaluate the significance of π-electron delocalization (π-ED) of 5/6 membered rings. These results clearly show that the π-ED of the benchmark systems increase with the formation or strengthening of the HB, which is in line with the resonance assisted hydrogen bond theory.

Hansch’s analysis application to chalcone synthesis by Claisen–Schmidt reaction based in DFT methodology

Chalcones are bioactive compounds obtained from either natural sources or synthetic procedures and widely used due to their several biological properties. The most common experimental methodology in obtaining these compounds is Claisen–Schmidt reaction, which is a particular type of aldolic condensation. In this work, we have synthesized 23 chalcones and by density functional theory (DFT) calculation, we have studied the difference in reactivity of the several benzaldehydes and their effects on the yield of this reaction. From molecular orbital descriptors were obtained two quantitative structure–reactivity relationship (QSRR) models based on Hansch’s analysis. The results of this study showed that, for the most benzaldehydes (15 of 23 compounds), their reactivity was correlated with LUMO energy and global Electrophilicity Index (ω) values, which are determined in the first step of Claisen–Schmidt condensation mechanism (nucleophilic addition). Likewise, for the smallest group of benzaldehydes, their reactivity was related to their HOMO and ΔL − H (LUMO − HOMO) energies, which were determined in the second step of the mechanism (trans-elimination). This is the first report of a QSRR model analyzing the yield of chalcone synthesis based on DFT methodology.

Boron nitride nanotubes for delivery of 5-fluorouracil as anticancer drug: a theoretical study

Abstract The electronic structure and properties of the armchair boron nitride nanotubes (BNNTs) interacted with the 5-FU drug, as an anticancer drug, are studied at the B3LYP/6-31G(d,p) level of theory. D3-Corrections were carried out for the treatment of intermolecular interactions in the hybrid complexes and encapsulated nanotubes, exactly. Results have shown that the encapsulation and adsorption of 5-FU molecule on the studied BNNTs surface are favorable processes, with a few exceptions. Also, it is found that the encapsulated nanotubes are stable than the hybrid complexes. Furthermore, we estimated the strengths of the intermolecular bonds of the benchmark systems by energetic, geometric, topological and molecular orbital descriptors. Some analyses have been made to explore any changes in the binding characteristics of the drug molecule after its attachment to the nanotubes. According to the NBO results, the charge transfer phenomenon is observed from the bonding or nonbonding orbitals of drug to the antibonding orbitals of BNNTs. Moreover, HOMO–LUMO analysis indicated that, after the adsorption process, the HOMO value slightly increased, while the LUMO value in these systems significantly reduced in the both of Drug@BNNTs groups. So, the energy gaps between HOMO and LUMO (Eg) are reduced, which emphasis on the greater intermolecular bond strength. Finally, the stability and reactivity of the Drug@BNNTs complexes have been examined from the magnitudes of the chemical reactivity descriptors such as chemical potential, global hardness, and electrophilicity index. As a consequence, BNNTs can be considered as a drug delivery vehicle for the transportation of 5-FU as anticancer drug within the biological systems.

Mutual effects of the cation-π, anion-π and intramolecular hydrogen bond in the various complexes of 1,3,5-triamino-2,4,6-trinitrobenzene with some cations (Li+, Na+, K+, Mg2+, Ca2+) and anions (F˗, Cl˗, Br˗)

A comprehensive theoretical investigation of the mutual effects of the cation-π, anion-π, and intramolecular hydrogen bond (IMHB) interactions in the various ternary complexes of 1,3,5-triamino-2,4,6-trinitrobenzene (ANB) with anions (A: F˗, Cl˗, Br˗) and cations (M: Li+, Na+, K+, Mg2+, Ca2+) were carried out. The energetic, geometrical, topological, and molecular orbital descriptors are employed to estimate the strength of the mentioned non-covalent interactions and their results were compared with the corresponding data of the ANB⋯M, ANB⋯A and A⋯Bz⋯M complexes, as a set of reference points. The results indicate that the presence of resonance-assisted hydrogen bond (RAHB) units decreases the strength of cation-π interaction while for anion-π interactions, the reverse process is observed. On the other hand, the RAHB units reduce the binding energies of the ternary complexes and cooperative effects between the cation-π and anion-π interactions, with respect to the A⋯Bz⋯M complexes. Furthermore, the coexistence of cation-π and anion-π interactions modulates their effects on the strength of IMHB. Finally, the harmonic oscillator model of aromaticity (HOMA) indicator was applied to analyze the influences of the mentioned interactions on the significance of the π-electron delocalization (π-ED) of the RAHB units and aromaticity of the benzene ring. It was found that the coexistence of cation-π and anion-π interactions effectively change the π˗ED and aromaticity.

The hydrogen-bonded complexes of the 5-fluorouracil with the DNA purine bases: a comprehensive quantum chemical study

In this research work, various hydrogen-bonded complexes of 5-fluorouracil (FU), as a simplest organic anticancer drug, with the adenine and guanine purine bases were investigated. First, the molecular electrostatic potentials (MEP) of all monomers (FU, A, and G) are explored and their active sites for hydrogen-bonded interactions identified. Then, the selected plausible coplanar complexes were optimized and their complexation energies obtained. Our results reveal that the FU-G complexes are more stable than the FU-A ones. Also, the most stable structures of both series were recognized, which is consistent with the MEP results of monomers. Additionally, we estimated the strengths of the individual hydrogen bonds of the benchmark systems by energetic, geometric, spectroscopic, topological, and molecular orbital descriptors. The acceptable linear correlations between the complexation energies and some of the mentioned descriptors are observed. Finally, several aromatic indices (HOMA, ATI, NICS (0), and NICS (1)) were applied to evaluate the significant of π-electron delocalization (π-ED) of 5/6 membered rings. These results show that the π-ED of the benchmark systems increases with the formation or strengthening of the HB, which is in line with the resonance-assisted hydrogen bond theory.

A comparative study of cooperative effects between the intramolecular hydrogen bond and cation···π interaction in various complexes of ortho-aminobenzaldehyde with its thio and seleno analogous

In the present study, a comparative study of cooperative effect between the intramolecular hydrogen bond (IMHB) and cation···π interactions for the first time in some complexes of ortho-aminobenzaldehyde with its thio and seleno analogues at the M062X/6-311++G(d, p) level of theory has been carried out. The energetic, geometric, spectroscopic, topologic and molecular orbital descriptors were used to evaluate the strength of the IMHB and cation···π interactions in the benchmark systems. Based on the energetic results, for the double-charge cations, the coexistence of these non-covalent interactions increases the strength of the cation···π, while for the mono-charge cations the reverse process is observed. However, for both type of the cations (mono- and double charges), this coupling leads to a stronger IMHB. In contrast to the energetic conclusions, the results of the other descriptors indicated that the coupling simultaneously strengthens both of the interactions . On the other hand, the harmonic oscillator model of aromaticity was applied to evaluate the significance of π-electron delocalization (π-ED) within the RAHB unit and aromaticity of benzene ring in the title complexes. These results revealed that the mentioned coupling decreased the π-ED and aromaticity. Furthermore, the change in strengths of the IMHB and cation···π interactions and also the significant of π-ED and aromaticity can be arranged in π···Mg2+ > π···Ca2+ > π···Li+> π···K+ > π···Na+ order. Finally, the sulfur and selenium atoms replaced instead of oxygen to explore their influences on the nature of IMHB, cation···π, π-ED and aromaticity.

Development of Prediction Models for the Reactivity of Organic Compounds with Ozone in Aqueous Solution by Quantum Chemical Calculations: The Role of Delocalized and Localized Molecular Orbitals.

Second-order rate constants (kO3) for the reaction of ozone with micropollutants are essential parameters for the assessment of micropollutant elimination efficiency during ozonation in water and wastewater treatment. Prediction models for kO3 were developed for aromatic compounds, olefins, and amines by quantum chemical molecular orbital calculations employing ab initio Hartree-Fock (HF) and density functional theory (B3LYP) methods. The kO3 values for aromatic compounds correlated well with the energy of a delocalized molecular orbital first appearing on an aromatic ring (i.e., the highest occupied molecular orbital (HOMO) or HOMO-n (n ≥ 0) when the HOMO is not located on the aromatic ring); the number of compounds tested (N) was 112, and the correlation coefficient (R(2)) values were 0.82-1.00. The kO3 values for olefins and amines correlated well with the energy of a localized molecular orbital (i.e., the natural bond orbital (NBO)) energy of the carbon-carbon π bond of olefins (N = 45, R(2) values of 0.82-0.85) and the NBO energy of the nitrogen lone-pair electrons of amines (N = 59, R(2) values of 0.81-0.83), respectively. Considering the performance of the kO3 prediction model and the computational costs, the HF/6-31G method is recommended for all aromatic groups and olefins investigated herein, whereas the HF/MIDI!, HF/6-31G*, or HF/6-311++G** methods are recommended for amines. Based on their mean absolute errors, the above models could predict kO3 within a factor of 4, on average, relative to the experimentally determined values. Overall, good correlations were also observed (R(2) values of 0.77-0.96) between kO3 predictions by quantum molecular orbital descriptors in this study and by the Hammett (σ) and Taft (σ*) constants from previously developed quantitative structure-activity relationship (QSAR) models. Hence, the quantum molecular orbital descriptors are an alternative to σ and σ*-values in QSAR applications and can also be utilized to estimate unknown σ or σ*-values. .

Multilinear Regression and Comparative Molecular Field Analysis (CoMFA) of Azo Dye—Fiber Affinities. Part 2. Inclusion of Solution‐Phase Molecular Orbital Descriptors.

Multilinear Regression and Comparative Molecular Field Analysis (CoMFA) of Azo Dye—Fiber Affinities. Part 2. Inclusion of Solution‐Phase Molecular Orbital Descriptors.

Partial Least Squares Modelling of the Acute Toxicity of Aliphatic Compounds to Tetrahymena pyriformis

The aim of this study was to evaluate a multivariate statistical model, utilising Partial Least Squares (PLS) analysis, for the prediction of the acute toxicity of aliphatic chemicals to the ciliate Tetrahymena pyriformis. A model was developed that was capable of making a prediction regardless the mechanism of toxic action. The toxicity of 476 compounds, possessing different mechanisms of toxic action was considered. A set of 74 descriptors, including the octanol–water partition coefficient, molecular-orbital descriptors, geometrical, topological and connectivity indices, was generated. A three-component, eight-descriptor PLS model was developed. It was validated by a Y-permutation test and by simulation of external prediction for complementary subsets. A comparison with existing class or mechanism-based models, derived on the same data set, was made.

Comparative Molecular Field Analysis (CoMFA) of Anionic Azo Dye‐Fiber Affinities I: Gas‐Phase Molecular Orbital Descriptors.

Comparative Molecular Field Analysis (CoMFA) of Anionic Azo Dye‐Fiber Affinities I: Gas‐Phase Molecular Orbital Descriptors.

MOLECULAR STRUCTURAL PARAMETERS IN TUBERCULOSTATIC ACTIVITY OF POLYHYDROXYXANTHONES

This investigation was undertaken to test the correlation of the observed tuberculostatic activity of a series of 7(2)-polyhydroxyxanthones 1a-j with their lipophilic parameters (Rm) as well as molecular orbital descriptors such as; dipole moment (dp); electro density (D); heat of formation (hf), torsion angle (tor); van der Waal forces (vdw), bond length (str) and bond angle (bnd). The Rm-values were calculated from the corresponding Rf­-values, determined using polyamide plates. The molecular orbital regressors were derived through semi-empirical calculations using MMX-computer program. QSAR analysis of the activity parameters (Ka, Log Ka, Ka* and logKa*) as dependent variables and Rm or combination of Rm and dummy parameters representing the substitution pattern of hydroxyl groups on ring C of the xanthone nucleus demonstrated an increase in the lipophilic character by itself which did not correlate (r» -0.42) with increased potency against Mycobacterium lufu. Permeability study using standard cellophane membrane showed that, the synthesized compounds were poorly penetrating and may act directly on the cell wall. On the contrary higher correlation (r= 0.91) was observed between the activity parameter (log Ka*) and the electron density at C-4.

Modeling reductive dehalogenation with quantum chemically derived descriptors.

Existing models for the reductive dehalogenation reaction under environmentally relevant conditions use Hammett and Taft coefficients as descriptors. Drawbacks of these descriptors are the limited possibilities for interpretation in terms of reaction mechanisms, and the limited availability of these descriptors for more "exotic' substituents. Therefore, in this study new descriptors are tested, using semi-empirical molecular orbital calculations. These descriptors are based on the energetic and electronic properties of the reaction sites and should be able to account for the systematics of the rate constants in a better way than substituent coefficient models. This approach is expected to give reliable estimates of the rate constants even for compounds containing less common structural features. Several relationships for a series of halogenated aromatics are presented here, relating the experimental rate constants to, among others, the calculated activation energy of the rate limiting step in the reductive dehalogenation process. Results show that semi-empirical molecular orbital descriptors are capable of describing the reaction kinetics within a homologous series of compounds. All descriptors can be explained for in terms of reaction mechanisms, thus corroborating the hypothesis about mechanisms taking place in the environment.

Comparative molecular field analysis (CoMFA), semiempirical (AM1) molecular orbital and multiconformational minimal steric difference (MTD) calculations of anthraquinone dye-fibre affinities

Comparative molecular field analysis (CoMFA), a three-dimensional quantitative structure-activity approach, was used to interpret the affinity of a series of anthraquinone vat dyes to cellulose fibres. The excellent correlation obtained by this method — even when using a quite small number (five) of components in the partial least-squares analysis (crossvalidated r cv 2 = 0.841, conventional r 2 = 0.992) — indicates that the dye-fibre interaction is largely dominated by steric and even more important electrostatic effects. Based on the CoMFA field contributions, suggestions for further activity enhancements can be made. Inclusion of molecular orbital (AM1) derived quantitative structure-activity relationship (QSAR) descriptors ( ϵ HOMO , ϵ LUMO and dipole moments μ) does not alter the picture derived from CoMFA fields alone. Of the molecular orbital descriptors, the LUMO orbital energy is found to yield the most important contribution. In addition, a multiconformational minimal steric difference (MTD) analysis, including several low-energy conformations of the investigated compounds, was done. This approach also indicated a good correlation with dye affinity ( r cv 2 = 0.827, r 2 = 0.941). The optimized receptor map is in accordance with the CoMFA electrostatic contour maps.