PM3 Results Research Articles

Host-guest complex of nabumetone: β-cyclodextrin: quantum chemical study and QTAIM analysis

The aim of the present work is the investigation of the inclusion complex of nabumetone (NAB) and β-cyclodextrin (β-CD) using PM3, DFT, DFT-D and ONIOM2 methods. The results indicate that the most energetically favorable structure predicts a preference of the methoxy group to enter the cavity of β-CD from its wide rim. Consequently, the butanone moiety is positioned outside the cavity on the side of the secondary hydroxyls, with a total insertion of naphthalene group. The semi-empirical PM3 results are in good agreement with those obtained by the DFT optimization (with and without dispersion correction). The donor–acceptor interactions between drug and the cavity wall of the host, studied on the basis of natural bonding orbital (NBO) analysis, show the presence of weak intermolecular hydrogen bonds in addition to the most important van der Waals interactions. Furthermore, it is revealed that among the DFT and DFT-D techniques selected to quantify these interactions, WB97X-D functional provides the greatest values of stabilization energies E(2). Finally, a detailed topological charge density analysis based on the quantum theory of atoms in molecules (QTAIM), developed by Bader and co-workers, has been accomplished using the WB97X-D and B3LYP methods on the most favorable complexes. A good correlation between the structural parameters and the electronic density is found.

Spectral and molecular modeling investigations of supramolecular complexes of mefenamic acid and aceclofenac with α- and β-cyclodextrin

Inclusion complexes of mefenamic acid (MFA) and aceclofenac (ALF) with α- and β-cyclodextrins (CDs) in aqueous medium were investigated by absorption, fluorescence, time-resolved fluorescence methods. The solid inclusion complexes between drugs and CDs were characterized by SEM, TEM, FT-IR, 1H NMR, DSC and powder XRD techniques. Spectral studies indicated that both CDs form 1:1 inclusion complex with MFA and ALF. The experimental results revealed that the inclusion process is a spontaneous process. Time-resolved fluorescence studies suggested that ALF exhibited biexponential decay in aqueous and triexponential decay in CD whereas significant enhancement of lifetime of decay components of MFA was observed. Morphologies of drug-CD complexes observed by TEM demonstrate that self-aggregates of MFA/α-CD, ALF/α-CD and ALF/β-CD were nano-sized particles while vesicles were observed for MFA/β-CD. A spatial arrangement of inclusion complex is proposed based on 1H NMR and PM3 results. Investigations of thermodynamic and electronic properties confirmed the stability of the inclusion complex.

Excimer emission in norepinephrine and epinephrine drugs with α- and β-cyclodextrins: spectral and molecular modeling studies.

The inclusion complexation behavior of norepinephrine (NORE) and epinephrine (EPIN) with native cyclodextrins (α-CD and β-CD) were investigated by UV-visible, fluorimetry, time-resolved fluorescence, SEM, TEM, FT-IR, (1)H NMR, DSC, powder XRD and PM3 methods. Single emission was observed in aqueous solution where as dual emission (excimer) noticed in the CD solutions. Both drugs form 1:1 drug-CD complexes in lower CD concentrations and 1:2 CD-drug2 complexes in the higher CD concentrations. Time-resolved fluorescence studies indicated that both drugs showed single exponential decay in water and biexponential decay in CD. Nano-sized self-aggregated particles of drug-CD were found by TEM studies. Molecular modeling studies indicated that aliphatic chain part of the drug was entrapped in the CD cavity. Thermodynamic parameters and binding affinity of complex formation of the CD were determined according to PM3 method. The PM3 results were in good agreement with the experimental results.

Investigation of inclusion complexes of sulfamerazine with α- and β-cyclodextrins: An experimental and theoretical study

Inclusion complexation behavior and binding ability of sulfamerazine (SMRZ) with α- and β-cyclodextrins (α-CD and β-CD) were investigated. The formation of inclusion complexes are studied by UV–visible, fluorescence, time-resolved fluorescence, 1H NMR, FT-IR, DSC, XRD, SEM, TEM and molecular modeling methods. Both experimental and PM3 results indicated that the SMRZ is partially encapsulated in the CD cavity. The different spectral shifts observed in both the CDs indicate that different types of inclusion complexes are formed. Nanosecond time-resolved fluorescence studies demonstrated that SMRZ exhibit biexponential decay in water and triexponential decay in CD solutions. The resonance of the aromatic protons of SMRZ showed remarkably upfield shift in the complexes suggested that the aniline ring deeply encapsulated in the CD cavity. The amino and amido stretching vibrations at 3483cm−1 and 3379cm−1 respectively are strongly affected in the inclusion complexes. DSC curves for the inclusion complexes exhibited a broad endothermic effect from 106.4°C, 123.8°C and 234.5 6°C for α-CD and 118.2°C and 231.4°C for β-CD. TEM images of both inclusion complexes are forms a nanochain like agglomerated structures with a width ranging from 40nm to 100nm. Thermodynamic parameters and binding affinity of the inclusion complex formation were determined and discussed.

A through-space charge transfer mechanism for explaining the oxidation of 2-chlorophenol on a tetrasulphonated nickel(III) phthalocyanine

In this work a mechanism is proposed to explain the oxidation of 2-chlorophenol (2-CP) mediated by a tetrasulphonated nickel(III) phthalocyanine (NiTSPc) in the gas phase with the density functional and wavefunction theories. Two hybrid density functionals (B3LYP, MPWB1K) in their unrestricted and restricted open form, and the unrestricted semiempirical Hartree–Fock PM3 method (UHF PM3) were applied. Using a supermolecule scheme (2-CP•••Ni(III)TSPc) and a reaction coordinate ( r Ni···O) denoted by the distance between Ni and O (2-CP), for the r Ni···O = 3.6–5.4 Å range we found that both functionals in their unrestricted and restricted open form showed a charge transfer (CT) of about 0.8–0.9 electrons from 2-CP towards NiTSPc, as obtained by the spin density and the Mulliken electronic population change. Similar results were obtained for UHF PM3 (one electron CT). Thus, our results showed that the oxidation of 2-chlorophenol follows a through-space mechanism. Calculations of the interaction energy carried out for the 2-CP•••Ni(III)TSPc supermolecule showed a trend towards the formation of a potential well for the r Ni···O = 3.8–5.0 Å region which was more apparent for the unrestricted methods (UB3LYP, UMPWB1K, UHF PM3). The energy minimum was obtained in the range 4.2–4.6 Å. However, in contrast with the PM3 results, we found that the density functionals used do not predict negative values for the interaction energy, confirming that in this case they fail to describe this kind of non-covalent interactions.

Research Article: Quantitative Structure Activity Relationship (QSAR) Study of Estrogen Derivatives Based on Descriptors of Energy and Softness

Quantum chemical interaction of estrogen derivatives with their receptor has been explored by using Klopman atomic softness. Four series of estrogen derivatives were taken from the literature and the structure of receptor (PDB code 1QKT) was obtained from the protein databank. It is proposed that three Lys, a His, a Tyr and a Cys residues are important for binding. The basic softness values (E(m)(double dagger)) and acidic softness values (E(n)(double dagger)) of all atoms of estrogen derivatives were evaluated. The required parameters for Klopman equation were taken from PM3 results. The highest E(n)(double dagger) values for each molecules and highest E(m)(double dagger) value for each residue were identified and Delta E(nm)(double dagger) has been derived using them. The lowest Delta E(nm)(double dagger) values were used in addition to Q(min) (highest negative charge), Delta H(f)(0) (heat of formation), E(T) (total energy), and E(E) (electronic energy). Multiple linear regression analysis was employed to correlate the variation of relative binding affinity values. The analyses show that Delta E(nm)(double dagger) values in combination with other descriptors provide significant correlation with relative binding affinity values. The result underscores that carbonyl oxygen of the receptor is important for interaction with estrogen derivatives. This model could be utilized to predict the binding affinity of a new compound of this series.

Can semi-empirical models describe HCl dissociation in water?

We discuss the failure of commonly used AM1 and PM3 semiempirical methods to correctly describe acid dissociation. We focus our analysis on HCl because of its physicochemical importance and its relevance in atmospheric chemistry. The structure of non-dissociated and dissociated HCl – (H2O) n clusters is accounted for. The very bad results obtained with PM3 (and also with AM1) are related to large errors in gas-phase proton affinity of water and gas-phase acidity of HCl. Indeed, estimation of pKa values shows that neither AM1 nor PM3 are able to predict HCl dissociation in liquid water since HCl is found to be a weaker acid than H3O+. We have proposed in previous works a modified PM3 approach (PM3-MAIS) adapted to intermolecular calculations. It is derived from PM3 by reparameterization of the core–core functions using ab initio data. Since parameters for H–Cl and O–Cl core–core interactions were not yet available, we have carried out the corresponding optimization. Application of the PM3-MAIS method to HCl dissociation in HCl–(H2O) n clusters leads to a huge improvement over PM3 results. Though the method predicts a slightly overestimated HCl acidity in water environment, the overall agreement with ab initio calculations is very satisfying and justifies efforts to develop new semiempirical methods.

Prediction of Low-Energy Isomers of Large Fullerenes from C132 to C160

To predict energetically favored isomers, we used a topological scheme as a prescreening tool to select candidate isomers for each fullerene from C(106) to C(160). Comparison with the PM3 and tight-binding (TB) potential calculated results and few published data for the low-energy isomers of C(106) to C(130) indicates that the prescreening approach is feasible. For each fullerene from C(132) up to C(160), the selected 1000 candidate isomers were further optimized by PM3 and TB potential. The analysis of the semiempirical PM3 and TB results of C(106) to C(160) provides some qualitative features of the large fullerenes. Furthermore, calculations at the B3LYP/6-31G*//B3LYP/3-21G level of theory were carried out on the top ten PM3 and TB low-energy isomers of C(132) to C(160) to accurately predict the stable isomers, and the HOMO-LUMO gap, the ionization energy, and electron affinity of the lowest-energy isomers were also investigated at the same level.

Highly Efficient One‐Pot Synthesis of 1‐Substituted‐1,2,3,4‐tetrahydropyrazino[1,2‐a]indoles.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Highly efficient one-pot synthesis of 1-substituted-1,2,3,4-tetrahydropyrazino[1,2- a]indoles

A practical and general one-pot synthesis of 1-substituted-10-methyl-1,2,3,4-tetrahydropyrazino[1,2- a]indoles is described. The approach uses 2-(3-methyl-1 H-indol-1-yl) ethylamine, benzotriazole and aldehydes in the presence of catalytic amount of acid catalysts (AlCl 3, ZnCl 2, ZnBr 2, p-TsOH, CH 3SO 3H) and proceeds in high yields via iminium cation intramolecular cyclization. The mechanism of the observed intramolecular cyclization reaction has been investigated theoretically by means of PM3 semiempirical method and results were consistent with the experimental results.

Estudo eletroquímico e químico-quântico da oxidação do antidepressivo tricíclico amitriptilina

This work presents the electrochemical and quantum chemical studies of the oxidation of the tricyclic antidepressant amitriptyline (AM) employing a carbon-polyurethane composite electrode (GPU) in a 0.1 mol L-1 BR buffer. The electrochemical results showed that the oxidation of AM occurs irreversibly at potentials close to 830 mV with the loss of one electron and one proton and is controlled by reagent and product adsorption. According to the PM3 results, the atom C16 is the region of highest probability for the oxidation of AM since it has the largest charge variation.

A quantum chemical study on structures of (+)-(R)-2,2-bis(diphenylphosphinoyl)-1,1′-binaphthyl and its hydroquinone complex

The (+)-(R)-2,2-bis(diphenylphosphinoyl)-1,1′-binaphthyl ((+)-(R)-BINAPO) and its cocrystal with hydroquinone (HQ) (1:1) were studied theoretically with AM1, PM3, MNDO and MINDO/3 semi-empirical methods to elucidate their structures. The bond lengths and angles from theoretical studies of molecules (+)-(R)-BINAPO and (+)-(R)-BINAPO/HQ with one molecule of water were found to be as expected. The results were compared with the previously obtained experimental data and MNDO and PM3 results were found to be the best fit for bond lengths and angles of (+)-(R)-BINAPO and for the complex of (+)-(R)-BINAPO/HQ, respectively.

Theoretical study of the hydrophobic character of the dimerization of dexanabinol

AbstractAn extensive theoretical study of the dimers of dexanabinol and related compounds has been performed at the ab initio Hartree–Fock (HF)/6‐31G** and B3LYP/6‐31G** levels. Theoretical calculations indicate that the most stable conformer of dexanabinol does not have intramolecular hydrogen bonds. The most stable dimer of dexanabinol forms intermolecular hydrogen bonds in which the phenol groups act as hydrogen bond donors and the allylic OH groups as acceptors is energetically more favored. The dimer results agree with previous PM3 results. In addition, the interaction of dexanabinol with two water molecules was studied. The effects of solvation were calculated with the Onsager model with full geometry optimization. The solvation results indicate that the most stable dimer of dexanabinol is affected little by solvation. © 2003 Wiley Periodicals, Inc. Int J Quantum Chem, 2004

Computational structural determination and energy landscape analysis of the hepatic carcinogen 2-(acetylamino)fluorene

2-(Acetylamino)fluorene (AAF), a potent mutagen and a prototypical example of the mutagenic aromatic amines, forms covalent adducts to DNA after metabolic activation in the liver. A benchmark study of AAF is presented using a number of the most widely used molecular mechanics and semiempirical computational methods and models. The results are compared to higher-level quantum calculations and to experimentally obtained crystal structures. Hydrogen bonding between AAF molecules in the crystal phase complicates the direct comparison of gas-phase theoretical calculations with experiment, so Hartree–Fock (HF) and Becke–Perdew (BP) density functional theory (DFT) calculations are used as benchmarks for the semiempirical and molecular mechanics results. Systematic conformer searches and dihedral energy landscapes were carried out for AAF using the SYBYL and MMFF94 molecular mechanics force fields; the AM1, PM3 and MNDO semiempirical quantum mechanics methods; HF using the 3-21G*and 6-31G* basis sets; and DFT using the nonlocal BP functional and double numerical polarization basis sets. MMFF94, AM1, HF and DFT calculations all predict the same planar structures, whereas SYBYL, MNDO and PM3 all predict various nonplanar geometries. The AM1 energy landscape is in substantial agreement with HF and DFT predictions; MMFF94 is qualitatively similar to HF and DFT; and the MNDO, PM3 and SYBYL results are qualitatively different from the HF and DFT results and from each other. These results are attributed to deficiencies in MNDO, PM3 and SYBYL. The MNDO, PM3 and SYBYL models may be unreliable for compounds in which an amide group is immediately adjacent to an aromatic ring.

A PM3 study of the molecular mechanism for the cycloaddition between cyclopentadiene and protonated pyridine-imine derivatives

The molecular mechanism of the cycloaddition reaction between cyclopentadiene (CP) and three pyridine-imine derivatives has been studied by means of PM3 semiempirical method. The role of the protonation, endo/exo and π-facial stereoselectivity are analyzed and discussed. In neutral conditions the cycloaddition between CP and the pyridine-imine takes place along a concerted mechanism. Protonation on both nitrogen atoms brings out that the reaction pathway takes with a very low barrier along a stepwise mechanism. PM3 results are capable to find the key factors governing this chemical reaction and to explain the experimental outcome.

Ab initio molecular orbital calculations on silica rings

The ab initio molecular orbital 3-21G method was applied to silica rings with two to six tetrahedra per ring. The geometries of the rings and their total electronic energies are compared with previous ab initio, AM1 and PM3 results and with experimental values for amorphous silica. The 3-21G method appears to reproduce with accuracy the experimental results. The semi-empirical PM3 method also gives results that compare favourably with the ab initio calculations and thus is concluded to be suitable for use in calculations on bigger silica clusters.

Photoelectron spectra and electronic structures of some indigo dyes

The He(I) photoelectron spectra of thioindigo ( 3), selenoindigo ( 4), bi(4,4-dimethyltetrahydropyrrole-3-one-2-ylidene) ( 5), bi(4,4-dimethyltetrahydrothiophene-3-one-2-ylidene) ( 6), octahydroindigo ( 8), 4,4'-dibutyl-5,5'-dimethylpyrrolindigo ( 9), and thiophenindigo ( 10) have been obtained by evaporating the compounds at temperatures up to about 350°C. The ionization potentials (IPs) are compared with those of the parent compound indigo ( 1) and are related to orbital energies or electronic states of the respective radical cations with the aid of semi-empirical SCF MO calculations. A satisfactory interpretation of the spectra is achieved with the Outer Valence Green's function method OVGF in combination with PM3 results. The first three IPs of all indigoid molecules in this study have the same origin, i.e. they relate to similar molecular orbitals. Because of the close relationship of the electronic structures of indigoid molecules, the IPs of the unknown unsubstituted pyrrolindigo ( 7) could be estimated.

Critical test of PM3-calculated proton transfer activation energies: a comparison with ab initio and AM1 calculations

Intra- and intermolecular proton transfer activation energies are calculated by means of the semiempirical PM3 method and compared with ab initio results obtained at MP2/6–31G ∗ or MP2/6–31G ∗∗ level. It is shown that corrections for zero-point vibrational energy (ZPVE) and thermal contributions do not affect the correlation between semiempirical and ab initio results. The linear relationship obtained suggests that PM3, in spite of some weaknesses, can be employed with a certain confidence to predict proton transfer activation barriers of large molecules or to obtain semi-quantitative trends for large numbers of interrelated systems. It is also shown that PM3 and AM1 results are of comparable quality for intramolecular proton transfers, whereas PM3 is to be preferred for intermolecular reactions, in particular when water molecules are involved.

A theoretical investigation on the reactivity of 6-amino-3-methylpyrimidin-4(3H)-ones towards DMAD. Tandem Diels-Alder retro Diels-Alder (DA/RDA) reaction

The reactivity of 6-aminopyrimidin-4(3H)-ones towards DMAD is successfully explained by theoretical investigation (PM3 semiempirical methods). All the PM3 results (activation energies (AE) for the transition states and the heat of formation ( ΔH) for the products) support our previous experimental work [J. Cobo et all. Synlett. 1993, 4 , 297–299; Tetrahedron 1994, 50 , 10345–10354]. In those reactions two main products were obtained: the pyridine derivatives 5 as major ones, which are formed by a tandem DA/RDA reaction with extrusion of the methylisocyanate fragment; and 5-ethenylpyrimidin-4(3H)-ones 10 as minor ones, which arised from a Michael addition, being in competition with the above normal DA.

Conformational analysis of diastereoisomeric tetraphenyl-substituted pyrrolidines

The relative configurations of a diastereoisomeric pair of tetraphenyl-substituted pyrrolidines were determined from NOE difference spectra. Low-temperature 1H NMR spectra indicate the presence of a conformational mixture in solution. According to computational conformational analysis utilizing molecular mechanics (MM2 and MM3), for the isomer with the two pairs of phenyl groups (2,5-cis and 3,4-cis) at different sides with respect to an average plane of the ring, both envelope and twist conformers are present. For the same isomer, AM1 and PM3 calculations determined a strong preference for the envelope conformer. For the other isomer (2,4,5-phenyls cis), the AM1 and PM3 results are in favour of twist conformers, while the molecular mechanics models and EHMO computed the envelope forms as having the lower energy. All computational methods are consistent in determining conformers from one and the same regions along the pseudorotational itinerary of the pyrrolidine ring as the most probable ones.