Harmonic Vibrational Frequencies Research Articles

Conformational analysis and spectroscopic properties of antichagasic nifurtimox

Considering the health relevance of Chagas' disease, recent research efforts have focused on developing more efficient drug delivery systems containing nifurtimox (NFX). This paper comprehensively investigates NFX through conformational analysis and spectroscopic characterization. Using a conformer-rotamer ensemble sampling tool (CREST-xtb), five distinct conformers of NFX were sampled within a 3.0 kcal mol−1 relative energy window. Subsequently, such structures were used as inputs for geometry optimization by density functional theory (DFT) at B3LYP-def2-TZVP level of theory. Notably, harmonic vibrational frequencies were calculated to establish an in-depth comparison with experimental results and existing literature for the NFX or similar molecules and functional groups, thereby achieving a widely reasoned assignment of the mid-infrared band absorptions for the first time. Moreover, UV–VIS spectra of NFX were obtained in several solvents, enabling the determination of the molar absorptivity coefficient for the two electronic transitions observed for NFX. Among the aprotic solvents, a bathochromic effect was observed in the function of the dielectric constants. Furthermore, a hypochromic effect was observed when the drug was dissolved in protic solvents. These findings offer crucial support for new drug delivery systems containing NFX while demonstrating the potential of spectrophotometric studies in establishing quality control assays for NFX drug products.

Relativistic coupled cluster study on the spectroscopic and radiative properties of the KFr molecule and modeling of the transport properties of potassium–francium dilute gas medium

The KFr diatomic molecule represents a promising candidate for photoassociation and indirect laser cooling. It has not yet been investigated experimentally and remains the only representative of the family of alkali-metal diatomics, which is scarcely researched theoretically. The potential energy curves of the states belonging to the three lowest dissociation limits of the KFr molecule are calculated using the Fock-space relativistic coupled cluster theory for the first time. Properties and parameters, such as electronic term energies, equilibrium internuclear distances, transition and permanent dipole moments, sequences of vibrational energies, harmonic vibrational frequencies, Franck–Condon factors, and radiative lifetimes (including bound and free transitions), are predicted. We analyzed and evaluated the probabilities of the two-step schemes (optical cycles) for the transfer process of the KFr molecules from excited vibronic states to the ground vibronic state. The transport properties (diffusion, viscosity, and thermal conductivity coefficients) of two-component dilute gas media of potassium and francium atoms as functions of the translation temperature up to 3000 K are also calculated. The data obtained would be useful for laser cooling and spectral experiments with KFr molecules.

A Charge-Charge Flux-Dipole Flux Analysis of Simple Molecular Systems with Halogen Bonds.

The presence of halogen bonds (R-X···B; R = substituent group, X = halogen, and B = Lewis base) provides quite amazing molecular systems for electronic structure investigations, presenting unique characteristics of fundamental relevance to supramolecular chemistry among other areas. Here, we use a double-hybrid approach from Density Functional Theory and triple-ζ basis sets augmented with diffuse functions (B2PLYP/def2-TZVPD) to deal with a large group of simple molecular systems containing halogen bonds (XBs), focusing on geometrical structures, binding energies, harmonic vibrational frequencies, and fundamental infrared intensities. Next, the electron densities and their variations on vibrations are carefully studied with the Quantum Theory of Atoms in Molecules (QTAIM) formalism and the charge-charge flux-dipole flux (CCFDF) model. We notice that the R-X stretching mode usually shows vibrational frequency decrements and infrared intensifications during the XB formation. Such features were also observed in hydrogen bonds, although the explanation for the band strengthening is different. Surprisingly, the most important contribution to these intensity increments due to complexation is now the interaction term between the charge flux and dipole flux (CF × DF). Thus, the use of atomic dipoles is mandatory to fully understand this phenomenon. In fact, the huge charge flux contributions to changes in dipole moment derivatives of R-X stretchings on halogen bonding are no longer accompanied by opposite variations of similar magnitudes in polarizations described by atomic dipole fluxes, which provided nearly unaltered values during the XB formation. Thus, the electronic charge flux direction change that takes place in complexes (from B to R) now reinforces dipole moment derivative terms from such atomic polarizations (mainly from the X atom). This intermolecular charge flux seems to be responsible for the unusual features noticed in the R-X stretching mode with the CCDDF/QTAIM model.

The Importance of Anharmonicity and Solvent Effects on the OH Radical Attack on Nucleobases.

Previous theoretical investigations of the reactions between an OH radical and a nucleobase have stated the most important pathways to be the C5-C6 addition for pyrimidines and the C8 addition for purines. Furthermore, the abstraction of a methyl hydrogen from thymine has also been proven an important pathway. The conclusions were based solely on gas-phase calculations and harmonic vibrational frequencies. In this paper, we supplement the calculations by applying solvent corrections through the polarizable continuum model (PCM) solvent model and applying anharmonicity in order to determine the importance of anharmonicity and solvent effects. Density functional theory (DFT) at the ωB97-D/6-311++G(2df,2pd) level with the Eckart tunneling correction is used. The total reaction rate constants are found to be 1.48 ×10-13 cm3 molecules-1s-1 for adenine, 1.02 ×10-11 cm3 molecules-1s-1 for guanine, 5.52 ×10-13 cm3 molecules-1s-1 for thymine, 1.47 ×10-13 cm3 molecules-1s-1 for cytosine and 7.59 ×10-14 cm3 molecules-1s-1 for uracil. These rates are found to be approximately two orders of magnitude larger than experimental values. We find that the tendencies observed for preferred pathways for reactions calculated in a solvent are comparable to the preferred pathways for reactions calculated in gas phase. We conclude that applying a solvent has a larger impact on more parameters compared to the inclusion of anharmonicity. For some reactions the inclusion of anharmonicity has no effect, whereas for others it does impact the energetics.

Cyanocyclopentadiene-Annulated Polycyclic Aromatic Radical Anions: Predicted Negative Ion Photoelectron Spectra and Singlet-Triplet Energies of Cyanoindene and Cyanofluorene Radical Anions.

Isomer-specific negative ion photoelectron spectra (NIPES) of cyanoindene (C9H7CN) and cyanofluorene (C14H9N), acquired through the computation of Franck-Condon (FC) factors that utilize harmonic vibrational frequencies and normal mode vectors derived from density functional theory (DFT) at the B3LYP/aug-cc-pVQZ and 6-311++G(2d,2p) basis sets, are reported. The adiabatic electron affinity (EA) values of the ground singlet (S0) and the lowest lying triplet (T1) states are used to predict site-specific S0-T1 energies (ΔEST). The vibrational spectra of the S0 and T1 states are typified by ring distortion and ring C-C stretching vibrational progressions. Among all the S0 isomers in C9H7CN, the 2-cyanoindene (2-C9H7CN) is found to be the most stable at an EA of 0.716 eV, with the least stable isomer being the 1-C9H7CN at an EA of 0.208 eV. In C14H9N, the most stable S0 isomer, 2-cyanofluorene (2-C14H9N), has an EA of 0.781 eV. The least stable S0 isomer in C14H9N is the 9-C14H9N, with an EA of 0.364 eV. The FC calculations are designed to mimic simulations that would be performed to aid in the analysis of experimental spectra obtained in NIPE spectroscopic techniques. The vibrational spectra, adiabatic EAs, and ΔEST values reported in this study are intended to act as a guide for future gas-phase ion spectroscopic experiments and astronomical searches, especially with regard to the hitherto largely unexplored C14H9N isomers.

Pb2H2 +: convergent quantum mechanical study of seven lead hydride cation structures. Toward laboratory identification

ABSTRACT Lead is heavily utilised in industry, but it bears potential harm due to its toxic nature. Identifying lead is important in diagnosing and preventing lead poisoning. Hydride generation via inductively-coupled plasma mass spectrometer (HG-ICP-MS) can detect small amounts of lead with high accuracy. Here we investigate seven structures of Pb 2 H 2 + . The geometries of each structure were optimised using coupled cluster with single, double, and perturbative triple excitations [CCSD(T)] method with the cc-pwCVQZ-PP basis set for lead and the cc-pVQZ basis set for hydrogen. Likewise, harmonic vibrational frequencies were obtained using the same method. Anharmonic frequencies were determined using CCSD(T) with cc-pwCVTZ-PP and cc-pVTZ basis sets for lead and hydrogen, respectively. The focal point approach (FPA), including CCSDT and CCSDT(Q) computations, was applied to the seven structures to find the relative energies with respect to the global minimum butterfly structure. Relative to the global minimum butterfly structure, the energies for the planar transition state, monobridged, vinylidene-like, trans, cis, and linear structures are: 1.1, 18.3, 26.5, 27.8, 28.8, and 93.7 kcal mol − 1 , respectively. Natural bond orders and dipole moments are reported as well. The predicted vibrational frequencies should be helpful in guiding the laboratory observation of Pb 2 H 2 + .

Exploring the Tl H potential energy surface: A comparative analysis with group 13 systems and experiment.

Thallium chemistry is experiencing unprecedented importance. Therefore, it is valuable to characterize some of the simplest thallium compounds. Stationary points along the singlet and triplet Tl H potential energy surface have been characterized. Stationary point geometries were optimized with the CCSD(T)/aug-cc-pwCVQZ-PP method. Harmonic vibrational frequencies were computed at the same level of theory while anharmonic vibrational frequencies were computed at the CCSD(T)/aug-cc-pwCVTZ-PP level of theory. Final energetics were obtained with the CCSDT(Q) method. Basis sets up to augmented quintuple-zeta cardinality (aug-cc-pwCV5Z-PP) were employed to obtain energetics in order to extrapolate to the complete basis set limits using the focal point approach. Zero-point vibrational energy corrections were appended to the extrapolated energies in order to determine relative energies at 0 K. It was found that the planar dibridged isomer lies lowest in energy while the linear structure lies highest in energy. The results were compared to other group 13 M H (M = B, Al, Ga, In, and Tl) theoretical studies and some interesting variations are found. With respect to experiment, incompatibilities exist.

Systematic analysis of electronic barrier heights and widths for concerted proton transfer in cyclic hydrogen bonded clusters: (HF)n, (HCl)n and (H2O)n where n = 3, 4, 5.

The MP2 and CCSD(T) methods are paired with correlation consistent basis sets as large as aug-cc-pVQZ to optimize the structures of the cyclic minima for (HF)n, (HCl)n and (H2O)n where n = 3-5, as well as the corresponding transition states (TSs) for concerted proton transfer (CPT). MP2 and CCSD(T) harmonic vibrational frequencies confirm the nature of each minimum and TS. Both conventional and explicitly correlated CCSD(T) computations are employed to assess the electronic dissociation energies and barrier heights for CPT near the complete basis (CBS) limit for all 9 clusters. Results for (HF)n are consistent with prior studies identifying Cnh and Dnh point group symmetry for the minima and TSs, respectively. Our computations also confirm that CPT proceeds through Cs TS structures for the C1 minima of (H2O)3 and (H2O)5, whereas the process goes through a TS with D2d symmetry for the S4 global minimum of (H2O)4. This work corroborates earlier findings that the minima for (HCl)3, (HCl)4 and (HCl)5 have C3h, S4 and C1 point group symmetry, respectively, and that the Cnh structures are not minima for n = 4 and 5. Moreover, our computations show the TSs for CPT in (HCl)3, (HCl)4 and (HCl)5 have D3h, D2d, and C2 point group symmetry, respectively. At the CCSD(T) CBS limit, (HF)4 and (HF)5 have the smallest electronic barrier heights for CPT (≈15 kcal mol-1 for both), followed by the HF trimer (≈21 kcal mol-1). The barriers are appreciably higher for the other clusters (around 27 kcal mol-1 for (H2O)4 and (HCl)3; roughly 30 kcal mol-1 for (H2O)3, (H2O)5 and (HCl)4; up to 38 kcal mol-1 for (HCl)5). At the CBS limit, MP2 significantly underestimates the CCSD(T) barrier heights (e.g., by ca. 2, 4 and 7 kcal mol-1 for the pentamers of HF, H2O and HCl, respectively), whereas CCSD overestimates these barriers by roughly the same magnitude. Scaling the barrier heights and dissociation energies by the number of fragments in the cluster reveals strong linear relationships between the two quantities and with the magnitudes of the imaginary vibrational frequency for the TSs.

The impact of solvation on the structure and electric field strength in Li+GlyGly complexes.

To scrutinise the impact of electric fields on the structure and vibrations of biomolecules in the presence of water, we study the sequential solvation of lithium diglycine up to three water molecules with cryogenic infrared action spectroscopy. Conformer-specific IR-IR spectroscopy and H2O/D2O isotopic substitution experiments provide most of the information required to decipher the structure of the observed conformers. Additional confirmation is provided by scaled harmonic vibrational frequency calculations using MP2 and DFT. The first water molecule is shown to bind to the Li+ ion, which weakens the electric field experienced by the peptide and as a consequence, also the strength of an internal NH⋯NH2 hydrogen bond in the diglycine backbone. The strength of this hydrogen bond decreases approximately linearly with the number of water molecules as a result of the decreasing electric field strength and coincides with an increase in the number of conformers observed in our spectra. The addition of two water molecules is already sufficient to change the preferred conformation of the peptide backbone, allowing for Li+ coordination to the lone pair of the terminal amine group.

Synthesis, spectroscopic, crystal structure and Hirshfeld surface analysis and DFT calculations of (E)-N-(2,6-dichlorophenyl)-1-(5-nitro-2-(piperidin-1-yl)phenyl) methanamine

In this study, experimental methods X-ray single crystal analysis, UV-vis spectroscopy and FT-IR spectroscopy, and theoretical methods Density Functional Theory (DFT) were used to study the structure of the new Schiff base (E)-N-(2,6-dichlorophenyl)-1-(5-nitro-2-(piperidin-1-yl)phenyl) methanamine. Theoretical calculations of the title compound and FT-IR harmonic vibration frequencies were carried out using B3LYP methods with the 6-31G(d,p) basis set. The optical properties have been studied by DFT calculation and the experimental UV-Vis spectrum presents its contribution to the HOMO-LUMO boundary. The molecular electrostatic potential map (MEP-ESP), analysis of frontier molecular orbitals (FMO), and determination of thermodynamic properties for the title compound were conducted using identical levels of theory. Besides, the structural state and crystal packing of the title compound were analyzed using molecular structure, Hirshfeld surfaces, interactions energies, energy frameworks and electrophilicity-based charge transfer (ECT) with DNA bases.

Analytic gradients for relativistic exact-two-component equation-of-motion coupled-cluster singles and doubles method.

A first implementation of analytic gradients for spinor-based relativistic equation-of-motion coupled-cluster singles and doubles method using an exact two-component Hamiltonian augmented with atomic mean-field spin-orbit integrals is reported. To demonstrate its applicability, we present calculations of equilibrium structures and harmonic vibrational frequencies for the electronic ground and excited states of the radium mono-amide molecule (RaNH2) and the radium mono-methoxide molecule (RaOCH3). Spin-orbit coupling is shown to quench Jahn-Teller effects in the first excited state of RaOCH3, resulting in a C3v equilibrium structure. The calculations also show that the radium atoms in these molecules serve as efficient optical cycling centers.

Ab initio investigation of the competition of pnicogen, halogen, and hydrogen bonds resulting from the interactions between cyanophosphine and hypohalous acids.

The complexes formed as a result of the interactions between cyanophosphine (CP, H2PCN) and hypohalous acid molecules (HOX, X = F, Cl, Br, and I) were studied by employing ab initio computations conducted at the MP2/aug-cc-pVTZ level. Three types of complexes were acquired (I, II, and III) as a result of the (O∙∙∙P) pnicogen bond, the (N∙∙∙H) hydrogen bond, and the (N∙∙∙X) halogen bond interaction, respectively. The results of harmonic vibrational frequency calculations with no imaginary frequencies confirmed the structures as minima. In addition, given the interaction energy of the complexes, hydrogen bond complexes of structure II have the highest stability compared to other structures. In all studied complexes, the strength of the interactions depended on the electronegativity of the halogen atoms. The characteristics and nature of the whole three types of complexes were examined and evaluated with natural bond orbital (NBO), atom in molecules (AIM), molecular electrostatic potential (MEP) maps, non-covalent interaction (NCI) index, and electron density difference (EDD) analyses. The optimization of all complexes and corresponding monomers was conducted through the ab initio method, employing the MP2 level along with the aug/cc-pVTZ basis set for all atoms, except for the iodine (I) atom, for which the aug-cc-pVTZ (PP) basis set was employed. Subsequent frequency calculations were executed to ascertain the minimum energy state of the complexes at the MP2 level and the aug/cc-pVTZ basis set, utilizing Gaussian09 software. The MEP maps of the monomers were generated using the analysis-surface suite (WFA-SAS) software package. To probe the orbital interactions within the studied complexes, NBO analysis was performed employing NBO software. The assessment of bond nature, topological features, and electron density values at critical points for the studied complexes was undertaken using AIMAll software. The NCI index was derived utilizing Multiwfn software, and its three-dimensional representation was rendered using VMD software.

Exploration of 4-Chloro-3-nitrocoumarin: Spectroscopic Analysis, DFT Insights, Molecular Docking, Assessments of Antibacterial and In Vitro Anticancer Activities as a Potent Bioactive Agent

The detailed theoretical and experimental (FT-IR, FT-Raman, UV-visible) spectroscopy analyses of the 4-Chloro-3-nitrocoumarin (CNC) molecule were carried out. The CNC compound's pharmacological properties were also investigated utilizing antibacterial and anticancer activity investigations. Initially, the CNC molecule was optimized by the density functional theory B3LYP method with a cc-pVTZ basis set using the Gaussian 09W program. The optimized molecular structure provides the harmonic vibrational frequencies of the CNC molecule. The observed and computed vibrational wavenumbers were assigned and found to be well correlated. UV-Vis absorption spectrum analysis indicates that the molecule contains π→π* electronic transition. Frontier molecular orbitals (FMOs) analysis indicates that the LUMO of CNC molecule is mainly located over the nitro group, it indicates that the nitro group is particularly prone to accepting electrons from other molecules and participate in chemical reactions where acts as an electrophile. Mulliken atomic charge distribution analysis further confirms the FMOs results. The antibacterial test results validate that the CNC molecule exhibits a stronger inhibitory effect on Staphylococcus aureus compared to the other tested bacteria. In vitro anticancer cytotoxicity analysis clearly evidences that the CNC compound inhibits the growth of HeLa cervical cancer cell lines more than A549 lung cancer cell lines. In silico molecular docking study further validates that the CNC molecule inhibits the function of the p38a Mitogen-activated protein kinase 14, which has been associated with cervical cancer. As a result, the present study paves the way for the development of new drugs to treat cervical cancer.
 Keywords: 4-Chloro-3-nitrocoumarin; DFT; FT-IR; FT-Raman; Anticancer; Molecular docking; Cervical cancer drug.

Insight into the Binding of Argon to Cyclic Water Clusters from Symmetry-Adapted Perturbation Theory.

This work systematically examines the interactions between a single argon atom and the edges and faces of cyclic H2O clusters containing three-five water molecules (Ar(H2O)n=3-5). Full geometry optimizations and subsequent harmonic vibrational frequency computations were performed using MP2 with a triple-ζ correlation consistent basis set augmented with diffuse functions on the heavy atoms (cc-pVTZ for H and aug-cc-pVTZ for O and Ar; denoted as haTZ). Optimized structures and harmonic vibrational frequencies were also obtained with the two-body-many-body (2b:Mb) and three-body-many-body (3b:Mb) techniques; here, high-level CCSD(T) computations capture up through the two-body or three-body contributions from the many-body expansion, respectively, while less demanding MP2 computations recover all higher-order contributions. Five unique stationary points have been identified in which Ar binds to the cyclic water trimer, along with four for (H2O)4 and three for (H2O)5. To the best of our knowledge, eleven of these twelve structures have been characterized here for the first time. Ar consistently binds more strongly to the faces than the edges of the cyclic (H2O)n clusters, by as much as a factor of two. The 3b:Mb electronic energies computed with the haTZ basis set indicate that Ar binds to the faces of the water clusters by at least 3 kJ mol-1 and by nearly 6 kJ mol-1 for one Ar(H2O)5 complex. An analysis of the interaction energies for the different binding motifs based on symmetry-adapted perturbation theory (SAPT) indicates that dispersion interactions are primarily responsible for the observed trends. The binding of a single Ar atom to a face of these cyclic water clusters can induce perturbations to the harmonic vibrational frequencies on the order of 5 cm-1 for some hydrogen-bonded OH stretching frequencies.

Accurate harmonic vibrational frequencies for diatomic molecules via quantum computing

Accurate harmonic vibrational frequencies for diatomic molecules via quantum computing

Lowest electronic states of neutral and ionic LiN

AbstractWe have investigated the potential energy curves (PECs) of the LiN heteronuclear diatomic molecule, including its ionic species LiN+ and LiN−, using explicitly correlated multi‐reference configuration interaction (MRCI‐F12) calculations in conjunction with the correlation consistent quintuple‐𝜁 basis set. The effect of core–valence correlation, scalar relativistic effects, and the size of the basis sets has been investigated. A comprehensive set of spectroscopic constants determined based on the above‐mentioned calculations are also reported for the lowest electronic states and all systems, including dissociation energies, harmonic and anharmonic vibrational frequencies, and rotational constants. Additional parameters, such as the dipole moments, equilibrium spin‐orbit constants, excitation energies, and rovibrational energy levels, are also documented. We found that the three triplet states of LiN, namely, X 3∑−, A 3Π, and 2 3∑−, exhibit substantial potential wells in the PEC diagrams, while the quintet states are repulsive in nature. The ground state of the anion also shows a deep potential well in the vicinity of its equilibrium geometry. In contrast, the ground and excited states of the cation are very loosely bound. Charge transfer properties of each of these states are also analyzed to obtain an in‐depth understanding of the interatomic interactions. We found that the core–valence correlation has a substantial effect on the calculated spectroscopic constants.

Simple Composite Approach to Efficiently Estimate Basis Set Limit CCSD(T) Harmonic Frequencies and Reaction Thermochemistry.

We introduce a simple strategy that combines the G3(MP2) composite method and explicitly correlated coupled cluster CCSD(T)-F12 method to efficiently estimate complete basis set CCSD(T) molecular geometries and harmonic vibrational frequencies at the cost of a double-ζ basis set calculation. Based on a large test set of 61 neutral, ionic, and open-shell molecules, and additionally 31 molecules in the HFREQ2014 data set, we demonstrate that this composite strategy has an average accuracy of 2 cm-1 or better relative to complete basis set CCSD(T) values. Using this approach, we estimated 696 CCSD(T)/CBS reaction energies of small to medium-sized systems containing up to 6 heavy atoms and confirmed existing approximations that use small basis set density functional theory methods [e.g., M06-2X/6-31+G(d)] to calculate thermal contributions to reaction enthalpies and Gibbs free energies that are accurate to within 0.2 kcal mol-1 on average.

Spectroscopic Characterization, Quantum Chemical, Molecular Docking, Antibacterial and Anticancer Studies on Ethyl Coumarin-3-Carboxylate: an Antibacterial and Lung Cancer Agent

The detailed theoretical and experimental (FT-IR, FT-Raman, UV-visible) spectroscopy analyses of the Ethyl Coumarin-3-Carboxylate (ECC) molecule were carried out. The ECC compound’s pharmacological properties were also investigated, utilizing antibacterial and anticancer activity investigations. Initially, the ECC molecule was optimized by the density functional theory B3LYP method with a 6-311 G++ (d,p) basis set using the Gaussian 09 W program. The optimized molecular structure provides the harmonic vibrational frequencies of the ECC molecule. The observed and computed vibrational wavenumbers were assigned and found to be well correlated. UV-Vis absorption spectrum analysis indicates that the molecule contains π →π* and n → π* electronic transitions. The Frontier molecular orbital analysis confirmed the molecular reactivity and bioactivity of ECC, while the Mulliken atomic charge distribution analysis pinpointed the molecule’s reactive sites. Antibacterial testing demonstrated the ECC compound’s inhibitory effect on various bacterial strains, with a particular impact on Klebsiella pneumonia. In vitro, anticancer assessments showcased ECC's stronger inhibitory effects on A549 lung cancer cell lines compared to HeLa cervical cancer cell lines. Additionally, in silico molecular docking investigations provided further validation that the ECC compound can inhibit the function of the epidermal growth factor receptor, a factor associated with lung cancer. As a result, this study lays the foundation for the development of novel drugs for lung cancer treatment.

Quantitative Structure-Activity Relationship (QSAR) Modelling of Indomethacin Derivatives Using Regression Analysis.

Indomethacin is a non-steroidal anti-inflammatory drug (NSAID) used for medication to reduce fever, spondylitis, or shoulder pain. It mainly works by the inhibition of prostaglandins, the endogenous signaling molecules. Fifteen indomethacin derivatives have been analyzed in relation to their physicochemical and molecular properties. Two-dimensional (2D) structures of fifteen indomethacin derivatives were drawn using the ACD Lab Chem Sketch version. Most of the topological parameters, such as wiener index (W), mean wiener index (Wa), Balaban indices (J), Balaban centric index (BAC), and molecular connectivity (χ), were calculated by using E Dragon software. The most common molecular file formats accepted in E-Dragon software were SMILES notations created online by Babel software and 2D structures of various derivatives, which were converted into 3D optimized structures using online CORINA, provided by Molecular Networks GMBH. 3D structures of compounds were also drawn on Gauss View software for calculations of various density functional theory (DFT) based quantum chemical descriptors, such as total energy (TE), softness (S), hardness (η), chemical potential (μ), highest occupied molecular orbital energy (HOMO), and lowest unoccupied molecular orbital energy (LUMO). All species were fully optimized in the gas phase with a 6-31+G* basis set. The harmonic vibrational frequency calculations were used to confirm that the optimized structures were minima, as characterized by positive vibrational frequencies. Combinations of various descriptors, such as D, ID, IOR, Log P, Mr, Mv, Mw, Pc, BAC, Pz, St, W, Wa, 0χ, 1χ, 2χ,3χ,4χ, 5χ, and Xeq have been found to be significant for modeling of activity. QSAR model no. 2: pIC50= -20.605 (±6.600) IOR - 0.747 (±0.454) I1 -5.083 (±3.478) Xeq + 51.647 optimized with empirical parameters with high statistical quality (R= 0.921, R2=0.848) was found to be the best model obtained. The QSAR model obtained suggests that substituents with a lesser value of the index of refraction and less electronegative groups were favourable for the activity, whereas indomethacin derivatives with a CH2CH2NHCONH (CH2)3ONO2 group at R1 position were unfavourable for the activity. The results were critically discussed based on regression data and cross-validation techniques. Pogliani factor Q and the results of the LOO (leave-one-out) method confirmed the reliability and predictability of the proposed models that could be highly beneficial for the future designing of new analogues with higher potency.

Competition between Solvent···Solvent and Solvent···Solute Interactions in the Microhydration of the Tetrafluoroborate Anion, BF4-(H2O)n=1,2,3,4.

This study systematically examines the interactions of the tetrafluoroborate anion (BF4-) with up to four water molecules (BF4-(H2O)n=1,2,3,4). Full geometry optimizations and subsequent harmonic vibrational frequency computations are performed using a variety of density functional theory (DFT) methods (B3LYP, B3LYP-D3BJ, and M06-2X) and the MP2 ab initio method with a triple-ζ correlation consistent basis set augmented with diffuse functions on all non-hydrogen atoms (cc-pVTZ for H and aug-cc-pVTZ for B, O, and F; denoted as haTZ). Optimized structures and harmonic vibrational frequencies were also obtained with the CCSD(T) ab initio method and the haTZ basis set for the mono- and dihydrate (n = 1, 2) structures. The 2-body:Many-body (2b:Mb) technique, in which CCSD(T) computations capture the 1- and 2-body contributions to the interactions and MP2 computations recover all higher-order contributions, was used to extend these demanding computations to the tri- and tetrahydrate (n = 3, 4) systems. Four, five, and eight new stationary points have been identified for the di-, tri-, and tetrahydrate systems, respectively. The global minimum of the monohydrate adopts a symmetric double ionic hydrogen bond motif with C2v symmetry and an electronic dissociation energy of 13.17 kcal mol-1 at the CCSD(T)/haTZ level of theory. This strong solvent···solute interaction, however, competes with solute···solute interactions in the lowest-energy BF4-(H2O)n=2,3,4 minima that are not seen in the other di-, tri-, or tetrahydrate minima. The latter interactions help increase the 2b:Mb dissociation energies to more than 26, 41, and 51 kcal mol-1 for n = 2, 3, and 4, respectively. Structures that form hydrogen bonds between the solvating water molecules also exhibit the largest shifts in the harmonic OH stretching frequencies for the waters of hydration. These shifts can exceed -280 cm-1 relative to an isolated H2O molecule at the 2b:Mb/haTZ level of theory.