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21 pages, 3580 KiB

Open AccessArticle

Insight into the Structural Determinants of Imidazole Scaffold-Based Derivatives as TNF-α Release Inhibitors by in Silico Explorations

by Yuan Wang, Mingwei Wu, Chunzhi Ai and Yonghua Wang

Int. J. Mol. Sci. 2015, 16(9), 20118-20138; https://doi.org/10.3390/ijms160920118 - 25 Aug 2015

Cited by 5 | Viewed by 5538

Abstract

Presently, 151 widely-diverse pyridinylimidazole-based compounds that show inhibitory activities at the TNF-α release were investigated. By using the distance comparison technique (DISCOtech), comparative molecular field analysis (CoMFA), and comparative molecular similarity index analysis (CoMSIA) methods, the pharmacophore models and the three-dimensional quantitative structure-activity [...] Read more.

Presently, 151 widely-diverse pyridinylimidazole-based compounds that show inhibitory activities at the TNF-α release were investigated. By using the distance comparison technique (DISCOtech), comparative molecular field analysis (CoMFA), and comparative molecular similarity index analysis (CoMSIA) methods, the pharmacophore models and the three-dimensional quantitative structure-activity relationships (3D-QSAR) of the compounds were explored. The proposed pharmacophore model, including two hydrophobic sites, two aromatic centers, two H-bond donor atoms, two H-bond acceptor atoms, and two H-bond donor sites characterizes the necessary structural features of TNF-α release inhibitors. Both the resultant CoMFA and CoMSIA models exhibited satisfactory predictability (with Q² (cross-validated correlation coefficient) = 0.557, R²_ncv (non-cross-validated correlation coefficient) = 0.740, R²_pre (predicted correlation coefficient) = 0.749 and Q² = 0.598, R²_ncv = 0.767, R²_pre = 0.860, respectively). Good consistency was observed between the 3D-QSAR models and the pharmacophore model that the hydrophobic interaction and hydrogen bonds play crucial roles in the mechanism of actions. The corresponding contour maps generated by these models provide more diverse information about the key intermolecular interactions of inhibitors with the surrounding environment. All these models have extended the understanding of imidazole-based compounds in the structure-activity relationship, and are useful for rational design and screening of novel 2-thioimidazole-based TNF-α release inhibitors. Full article

(This article belongs to the Special Issue Chemical Bond and Bonding 2015)

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49 pages, 4364 KiB

Open AccessArticle

Double Variational Binding—(SMILES) Conformational Analysis by Docking Mechanisms for Anti-HIV Pyrimidine Ligands

by Mihai V. Putz, Nicoleta A. Dudaș and Adriana Isvoran

Int. J. Mol. Sci. 2015, 16(8), 19553-19601; https://doi.org/10.3390/ijms160819553 - 18 Aug 2015

Cited by 8 | Viewed by 7652

Abstract

Variational quantitative binding–conformational analysis for a series of anti-HIV pyrimidine-based ligands is advanced at the individual molecular level. This was achieved by employing ligand-receptor docking algorithms for each molecule in the 1,3-disubstituted uracil derivative series that was studied. Such computational algorithms were employed [...] Read more.

Variational quantitative binding–conformational analysis for a series of anti-HIV pyrimidine-based ligands is advanced at the individual molecular level. This was achieved by employing ligand-receptor docking algorithms for each molecule in the 1,3-disubstituted uracil derivative series that was studied. Such computational algorithms were employed for analyzing both genuine molecular cases and their simplified molecular input line entry system (SMILES) transformations, which were created via the controlled breaking of chemical bonds, so as to generate the longest SMILES molecular chain (LoSMoC) and Branching SMILES (BraS) conformations. The study identified the most active anti-HIV molecules, and analyzed their special and relevant bonding fragments (chemical alerts), and the recorded energetic and geometric docking results (i.e., binding and affinity energies, and the surface area and volume of bonding, respectively). Clear computational evidence was also produced concerning the ligand-receptor pocket binding efficacies of the LoSMoc and BraS conformation types, thus confirming their earlier presence (as suggested by variational quantitative structure-activity relationship, variational-QSAR) as active intermediates for the molecule-to-cell transduction process. Full article

(This article belongs to the Special Issue Chemical Bond and Bonding 2015)

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18 pages, 3167 KiB

Open AccessArticle

Formation of Chlorotriophenoxy Radicals from Complete Series Reactions of Chlorotriophenols with H and OH Radicals

by Fei Xu, Xiangli Shi, Qingzhu Zhang and Wenxing Wang

Int. J. Mol. Sci. 2015, 16(8), 18714-18731; https://doi.org/10.3390/ijms160818714 - 11 Aug 2015

Cited by 11 | Viewed by 5380

Abstract

The chlorothiophenoxy radicals (CTPRs) are key intermediate species in the formation of polychlorinated dibenzothiophenes/thianthrenes (PCDT/TAs). In this work, the formation of CTPRs from the complete series reactions of 19 chlorothiophenol (CTP) congeners with H and OH radicals were investigated theoretically by using the [...] Read more.

The chlorothiophenoxy radicals (CTPRs) are key intermediate species in the formation of polychlorinated dibenzothiophenes/thianthrenes (PCDT/TAs). In this work, the formation of CTPRs from the complete series reactions of 19 chlorothiophenol (CTP) congeners with H and OH radicals were investigated theoretically by using the density functional theory (DFT) method. The profiles of the potential energy surface were constructed at the MPWB1K/6-311+G(3df,2p)//MPWB1K/6-31+G(d,p) level. The rate constants were evaluated by the canonical variational transition-state (CVT) theory with the small curvature tunneling (SCT) contribution at 600–1200 K. The present study indicates that the structural parameters, thermal data, and rate constants as well as the formation potential of CTPRs from CTPs are strongly dominated by the chlorine substitution at the ortho-position of CTPs. Comparison with the study of formation of chlorophenoxy radicals (CPRs) from chlorophenols (CPs) clearly shows that the thiophenoxyl-hydrogen abstraction from CTPs by H is more efficient than the phenoxyl-hydrogen abstraction from CPs by H, whereas the thiophenoxyl-hydrogen abstraction from CTPs by OH is less impactful than the phenoxyl-hydrogen abstraction from CPs by OH. Reactions of CTPs with H can occur more readily than that of CTPs with OH, which is opposite to the reactivity comparison of CPs with H and OH. Full article

(This article belongs to the Special Issue Chemical Bond and Bonding 2015)

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17 pages, 1225 KiB

Open AccessArticle

A Combined Pharmacophore Modeling, 3D QSAR and Virtual Screening Studies on Imidazopyridines as B-Raf Inhibitors

by Huiding Xie, Lijun Chen, Jianqiang Zhang, Xiaoguang Xie, Kaixiong Qiu and Jijun Fu

Int. J. Mol. Sci. 2015, 16(6), 12307-12323; https://doi.org/10.3390/ijms160612307 - 29 May 2015

Cited by 25 | Viewed by 6740

Abstract

B-Raf kinase is an important target in treatment of cancers. In order to design and find potent B-Raf inhibitors (BRIs), 3D pharmacophore models were created using the Genetic Algorithm with Linear Assignment of Hypermolecular Alignment of Database (GALAHAD). The best pharmacophore model obtained [...] Read more.

B-Raf kinase is an important target in treatment of cancers. In order to design and find potent B-Raf inhibitors (BRIs), 3D pharmacophore models were created using the Genetic Algorithm with Linear Assignment of Hypermolecular Alignment of Database (GALAHAD). The best pharmacophore model obtained which was used in effective alignment of the data set contains two acceptor atoms, three donor atoms and three hydrophobes. In succession, comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were performed on 39 imidazopyridine BRIs to build three dimensional quantitative structure-activity relationship (3D QSAR) models based on both pharmacophore and docking alignments. The CoMSIA model based on the pharmacophore alignment shows the best result (q² = 0.621, r²_pred = 0.885). This 3D QSAR approach provides significant insights that are useful for designing potent BRIs. In addition, the obtained best pharmacophore model was used for virtual screening against the NCI2000 database. The hit compounds were further filtered with molecular docking, and their biological activities were predicted using the CoMSIA model, and three potential BRIs with new skeletons were obtained. Full article

(This article belongs to the Special Issue Chemical Bond and Bonding 2015)

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11 pages, 1172 KiB

Open AccessShort Note

Acetic Acid-Catalyzed Formation of N-Phenylphthalimide from Phthalanilic Acid: A Computational Study of the Mechanism

by Ohgi Takahashi, Ryota Kirikoshi and Noriyoshi Manabe

Int. J. Mol. Sci. 2015, 16(6), 12174-12184; https://doi.org/10.3390/ijms160612174 - 28 May 2015

Cited by 5 | Viewed by 7812

Abstract

In glacial acetic acid, phthalanilic acid and its monosubstituents are known to be converted to the corresponding phthalimides in relatively good yields. In this study, we computationally investigated the experimentally proposed two-step (addition-elimination or cyclization-dehydration) mechanism at the second-order Møller-Plesset perturbation (MP2) level [...] Read more.

In glacial acetic acid, phthalanilic acid and its monosubstituents are known to be converted to the corresponding phthalimides in relatively good yields. In this study, we computationally investigated the experimentally proposed two-step (addition-elimination or cyclization-dehydration) mechanism at the second-order Møller-Plesset perturbation (MP2) level of theory for the unsubstituted phthalanilic acid, with an explicit acetic acid molecule included in the calculations. In the first step, a gem-diol tetrahedral intermediate is formed by the nucleophilic attack of the amide nitrogen. The second step is dehydration of the intermediate to give N-phenylphthalimide. In agreement with experimental findings, the second step has been shown to be rate-determining. Most importantly, both of the steps are catalyzed by an acetic acid molecule, which acts both as proton donor and acceptor. The present findings, along with those from our previous studies, suggest that acetic acid and other carboxylic acids (in their undissociated forms) can catalyze intramolecular nucleophilic attacks by amide nitrogens and breakdown of the resulting tetrahedral intermediates, acting simultaneously as proton donor and acceptor. In other words, double proton transfers involving a carboxylic acid molecule can be part of an extensive bond reorganization process from cyclic hydrogen-bonded complexes. Full article

(This article belongs to the Special Issue Chemical Bond and Bonding 2015)

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20 pages, 2126 KiB

Open AccessArticle

Crystal Structure, Chemical Bonding and Magnetism Studies for Three Quinary Polar Intermetallic Compounds in the (Eu_1−xCa_x)₉In₈(Ge_1−ySn_y)₈ (x = 0.66, y = 0.03) and the (Eu_1−xCa_x)₃In(Ge_3−ySn_1+y) (x = 0.66, 0.68; y = 0.13, 0.27) Phases

by Hyein Woo, Eunyoung Jang, Jin Kim, Yunho Lee, Jongsik Kim and Tae-Soo You

Int. J. Mol. Sci. 2015, 16(4), 9017-9036; https://doi.org/10.3390/ijms16049017 - 22 Apr 2015

Cited by 16 | Viewed by 7008

Abstract

Three quinary polar intermetallic compounds in the (Eu_1−xCa_x)₉In₈(Ge_1−ySn_y)₈ (x = 0.66, y = 0.03) and the (Eu_1−xCa_x)₃In(Ge_3-ySn [...] Read more.

Three quinary polar intermetallic compounds in the (Eu_1−xCa_x)₉In₈(Ge_1−ySn_y)₈ (x = 0.66, y = 0.03) and the (Eu_1−xCa_x)₃In(Ge_3-ySn_1+y) (x = 0.66, 0.68; y = 0.13, 0.27) phases have been synthesized using the molten In-metal flux method, and the crystal structures are characterized by powder and single-crystal X-ray diffractions. Two orthorhombic structural types can be viewed as an assembly of polyanionic frameworks consisting of the In(Ge/Sn)₄ tetrahedral chains, the bridging Ge₂ dimers, either the annulene-like “12-membered rings” for the (Eu_1−xCa_x)₉In₈(Ge_1−ySn_y)₈ series or the cis-trans Ge/Sn-chains for the (Eu_1−xCa_x)₃In(Ge_3−ySn_1+y) series, and several Eu/Ca-mixed cations. The most noticeable difference between two structural types is the amount and the location of the Sn-substitution for Ge: only a partial substitution (11%) occurs at the In(Ge/Sn)₄ tetrahedron in the (Eu_1−xCa_x)₉In₈(Ge_1−ySn_y)₈ series, whereas both a complete and a partial substitution (up to 27%) are observed, respectively, at the cis-trans Ge/Sn-chain and at the In(Ge/Sn)₄ tetrahedron in the (Eu_1−xCa_x)₃In(Ge_3−ySn_1+y) series. A series of tight-binding linear muffin-tin orbital calculations is conducted to understand overall electronic structures and chemical bonding among components. Magnetic susceptibility measurement indicates a ferromagnetic ordering of Eu atoms below 5 K for Eu_1.02(1)Ca_1.98InGe_2.87(1)Sn_1.13. Full article

(This article belongs to the Special Issue Chemical Bond and Bonding 2015)

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38 pages, 1042 KiB

Open AccessArticle

Chemical Bonding: The Orthogonal Valence-Bond View

by Alexander F. Sax

Int. J. Mol. Sci. 2015, 16(4), 8896-8933; https://doi.org/10.3390/ijms16048896 - 21 Apr 2015

Cited by 5 | Viewed by 7148

Abstract

Chemical bonding is the stabilization of a molecular system by charge- and spin-reorganization processes in chemical reactions. These processes are said to be local, because the number of atoms involved is very small. With multi-configurational self-consistent field (MCSCF) wave functions, these processes can [...] Read more.

Chemical bonding is the stabilization of a molecular system by charge- and spin-reorganization processes in chemical reactions. These processes are said to be local, because the number of atoms involved is very small. With multi-configurational self-consistent field (MCSCF) wave functions, these processes can be calculated, but the local information is hidden by the delocalized molecular orbitals (MO) used to construct the wave functions. The transformation of such wave functions into valence bond (VB) wave functions, which are based on localized orbitals, reveals the hidden information; this transformation is called a VB reading of MCSCF wave functions. The two-electron VB wave functions describing the Lewis electron pair that connects two atoms are frequently called covalent or neutral, suggesting that these wave functions describe an electronic situation where two electrons are never located at the same atom; such electronic situations and the wave functions describing them are called ionic. When the distance between two atoms decreases, however, every covalent VB wave function composed of non-orthogonal atomic orbitals changes its character from neutral to ionic. However, this change in the character of conventional VB wave functions is hidden by its mathematical form. Orthogonal VB wave functions composed of orthonormalized orbitals never change their character. When localized fragment orbitals are used instead of atomic orbitals, one can decide which local information is revealed and which remains hidden. In this paper, we analyze four chemical reactions by transforming the MCSCF wave functions into orthogonal VB wave functions; we show how the reactions are influenced by changing the atoms involved or by changing their local symmetry. Using orthogonal instead of non-orthogonal orbitals is not just a technical issue; it also changes the interpretation, revealing the properties of wave functions that remain otherwise undetected. Full article

(This article belongs to the Special Issue Chemical Bond and Bonding 2015)

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12 pages, 2327 KiB

Open AccessArticle

Decisive Interactions between the Heterocyclic Moiety and the Cluster Observed in Polyoxometalate-Surfactant Hybrid Crystals

by Saki Otobe, Natsumi Fujioka, Takuro Hirano, Eri Ishikawa, Haruo Naruke, Katsuhiko Fujio and Takeru Ito

Int. J. Mol. Sci. 2015, 16(4), 8505-8516; https://doi.org/10.3390/ijms16048505 - 16 Apr 2015

Cited by 6 | Viewed by 5701

Abstract

Inorganic-organic hybrid crystals were successfully obtained as single crystals by using polyoxotungstate anion and cationic dodecylpyridazinium (C₁₂pda) and dodecylpyridinium (C₁₂py) surfactants. The decatungstate (W₁₀) anion was used as the inorganic component, and the crystal structures were compared. [...] Read more.

Inorganic-organic hybrid crystals were successfully obtained as single crystals by using polyoxotungstate anion and cationic dodecylpyridazinium (C₁₂pda) and dodecylpyridinium (C₁₂py) surfactants. The decatungstate (W₁₀) anion was used as the inorganic component, and the crystal structures were compared. In the crystal comprising C₁₂pda (C₁₂pda-W₁₀), the heterocyclic moiety directly interacted with W₁₀, which contributed to a build-up of the crystal structure. On the other hand, the crystal consisting of C₁₂py (C₁₂py-W₁₀) had similar crystal packing and molecular arrangement to those in the W₁₀ crystal hybridized with other pyridinium surfactants. These results indicate the significance of the heterocyclic moiety of the surfactant to construct hybrid crystals with polyoxometalate anions. Full article

(This article belongs to the Special Issue Chemical Bond and Bonding 2015)

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17 pages, 197 KiB

Open AccessArticle

From ELF to Compressibility in Solids

by Julia Contreras-García, Miriam Marqués, José Manuel Menéndez and José Manuel Recio

Int. J. Mol. Sci. 2015, 16(4), 8151-8167; https://doi.org/10.3390/ijms16048151 - 13 Apr 2015

Cited by 11 | Viewed by 6339

Abstract

Understanding the electronic nature of materials’ compressibility has alwaysbeen a major issue behind tabulation and rationalization of bulk moduli. This is especiallybecause this understanding is one of the main approaches to the design and proposal of newmaterials with a desired (e.g., ultralow) compressibility. [...] Read more.

Understanding the electronic nature of materials’ compressibility has alwaysbeen a major issue behind tabulation and rationalization of bulk moduli. This is especiallybecause this understanding is one of the main approaches to the design and proposal of newmaterials with a desired (e.g., ultralow) compressibility. It is well recognized that the softestpart of the solid will be the one responsible for its compression at the first place. In chemicalterms, this means that the valence will suffer the main consequences of pressurization.It is desirable to understand this response to pressure in terms of the valence properties(charge, volume, etc.). One of the possible approaches is to consider models of electronicseparability, such as the bond charge model (BCM), which provides insight into the cohesionof covalent crystals in analogy with the classical ionic model. However, this model relies onempirical parametrization of bond and lone pair properties. In this contribution, we havecoupled electron localization function (ELF) ab initio data with the bond charge modeldeveloped by Parr in order to analyze solid state compressibility from first principles andmoreover, to derive general trends and shed light upon superhard behavior. Full article

(This article belongs to the Special Issue Chemical Bond and Bonding 2015)

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12 pages, 1210 KiB

Open AccessArticle

Glycolic Acid-Catalyzed Deamidation of Asparagine Residues in Degrading PLGA Matrices: A Computational Study

by Noriyoshi Manabe, Ryota Kirikoshi and Ohgi Takahashi

Int. J. Mol. Sci. 2015, 16(4), 7261-7272; https://doi.org/10.3390/ijms16047261 - 31 Mar 2015

Cited by 12 | Viewed by 6760

Abstract

Poly(lactic-co-glycolic acid) (PLGA) is a strong candidate for being a drug carrier in drug delivery systems because of its biocompatibility and biodegradability. However, in degrading PLGA matrices, the encapsulated peptide and protein drugs can undergo various degradation reactions, including deamidation at [...] Read more.

Poly(lactic-co-glycolic acid) (PLGA) is a strong candidate for being a drug carrier in drug delivery systems because of its biocompatibility and biodegradability. However, in degrading PLGA matrices, the encapsulated peptide and protein drugs can undergo various degradation reactions, including deamidation at asparagine (Asn) residues to give a succinimide species, which may affect their potency and/or safety. Here, we show computationally that glycolic acid (GA) in its undissociated form, which can exist in high concentration in degrading PLGA matrices, can catalyze the succinimide formation from Asn residues by acting as a proton-transfer mediator. A two-step mechanism was studied by quantum-chemical calculations using Ace-Asn-Nme (Ace = acetyl, Nme = NHCH₃) as a model compound. The first step is cyclization (intramolecular addition) to form a tetrahedral intermediate, and the second step is elimination of ammonia from the intermediate. Both steps involve an extensive bond reorganization mediated by a GA molecule, and the first step was predicted to be rate-determining. The present findings are expected to be useful in the design of more effective and safe PLGA devices. Full article

(This article belongs to the Special Issue Chemical Bond and Bonding 2015)

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18 pages, 1570 KiB

Open AccessArticle

Towards Understanding the Decomposition/Isomerism Channels of Stratospheric Bromine Species: Ab Initio and Quantum Topology Study

by Saadullah G. Aziz, Abdulrahman O. Alyoubi, Shaaban A. Elroby, Osman I. Osman and Rifaat H. Hilal

Int. J. Mol. Sci. 2015, 16(4), 6783-6800; https://doi.org/10.3390/ijms16046783 - 25 Mar 2015

Cited by 7 | Viewed by 6244

Abstract

The present study aims at a fundamental understanding of bonding characteristics of the C–Br and O–Br bonds. The target molecular systems are the isomeric CH₃OBr/BrCH₂OH system and their decomposition products. Calculations of geometries and frequencies at different density functional [...] Read more.

The present study aims at a fundamental understanding of bonding characteristics of the C–Br and O–Br bonds. The target molecular systems are the isomeric CH₃OBr/BrCH₂OH system and their decomposition products. Calculations of geometries and frequencies at different density functional theory (DFT) and Hartree–Fock/Møller–Plesset (HF/MP2) levels have been performed. Results have been assessed and evaluated against those obtained at the coupled cluster single-double (Triplet) (CCSD(T)) level of theory. The characteristics of the C–Br and O–Br bonds have been identified via analysis of the electrostatic potential, natural bond orbital (NBO), and quantum theory of atoms in molecules (QTAIM). Analysis of the electrostatic potential (ESP) maps enabled the quantitative characterization of the Br σ-holes. Its magnitude seems very sensitive to the environment and the charge accumulated in the adjacent centers. Some quantum topological parameters, namely Ñ²ρ, ellipticity at bond critical points and the Laplacian bond order, were computed and discussed. The potential energy function for internal rotation has been computed and Fourier transformed to characterize the conformational preferences and origin of the barriers. NBO energetic components for rotation about the C–Br and O–Br bonds as a function of torsion angle have been computed and displayed. Full article

(This article belongs to the Special Issue Chemical Bond and Bonding 2015)

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17 pages, 5608 KiB

Open AccessArticle

Exploring the Nature of Silicon-Noble Gas Bonds in H₃SiNgNSi and HSiNgNSi Compounds (Ng = Xe, Rn)

by Sudip Pan, Ranajit Saha and Pratim K. Chattaraj

Int. J. Mol. Sci. 2015, 16(3), 6402-6418; https://doi.org/10.3390/ijms16036402 - 19 Mar 2015

Cited by 39 | Viewed by 7702

Abstract

Ab initio and density functional theory-based computations are performed to investigate the structure and stability of H₃SiNgNSi and HSiNgNSi compounds (Ng = Xe, Rn). They are thermochemically unstable with respect to the dissociation channel producing Ng and H₃SiNSi or [...] Read more.

Ab initio and density functional theory-based computations are performed to investigate the structure and stability of H₃SiNgNSi and HSiNgNSi compounds (Ng = Xe, Rn). They are thermochemically unstable with respect to the dissociation channel producing Ng and H₃SiNSi or HSiNSi. However, they are kinetically stable with respect to this dissociation channel having activation free energy barriers of 19.3 and 23.3 kcal/mol for H₃SiXeNSi and H₃SiRnNSi, respectively, and 9.2 and 12.8 kcal/mol for HSiXeNSi and HSiRnNSi, respectively. The rest of the possible dissociation channels are endergonic in nature at room temperature for Rn analogues. However, one three-body dissociation channel for H₃SiXeNSi and one two-body and one three-body dissociation channels for HSiXeNSi are slightly exergonic in nature at room temperature. They become endergonic at slightly lower temperature. The nature of bonding between Ng and Si/N is analyzed by natural bond order, electron density and energy decomposition analyses. Natural population analysis indicates that they could be best represented as (H₃SiNg)⁺(NSi)⁻ and (HSiNg)⁺(NSi)⁻. Energy decomposition analysis further reveals that the contribution from the orbital term (ΔE_orb) is dominant (ca. 67%–75%) towards the total attraction energy associated with the Si-Ng bond, whereas the electrostatic term (ΔE_elstat) contributes the maximum (ca. 66%–68%) for the same in the Ng–N bond, implying the covalent nature of the former bond and the ionic nature of the latter. Full article

(This article belongs to the Special Issue Chemical Bond and Bonding 2015)

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21 pages, 2410 KiB

Open AccessArticle

Multiscale Experimental and Theoretical Investigations of Spin Crossover Fe^II Complexes: Examples of [Fe(phen)₂(NCS)₂] and [Fe(PM-BiA)₂(NCS)₂]

by Samir F. Matar, Philippe Guionneau and Guillaume Chastanet

Int. J. Mol. Sci. 2015, 16(2), 4007-4027; https://doi.org/10.3390/ijms16024007 - 12 Feb 2015

Cited by 16 | Viewed by 8280

Abstract

For spin crossover (SCO) complexes, computation results are reported and confirmed with experiments at multiscale levels of the isolated molecule and extended solid on the one hand and theory on the other hand. The SCO phenomenon which characterizes organometallics based on divalent iron [...] Read more.

For spin crossover (SCO) complexes, computation results are reported and confirmed with experiments at multiscale levels of the isolated molecule and extended solid on the one hand and theory on the other hand. The SCO phenomenon which characterizes organometallics based on divalent iron in an octahedral FeN₆-like environment with high spin (HS) and low spin (LS) states involves the LS/HS switching at the cost of small energies provided by temperature, pressure or light, the latter connected with Light-Induced Excited Spin-State Trapping (LIESST) process. Characteristic infra red (IR) and Raman vibration frequencies are computed within density functional theory (DFT) framework. In [Fe(phen)₂(NCS)₂] a connection of selected frequencies is established with an ultra-fast light-induced LS → HS photoswitching mechanism. In the extended solid, density of state DOS and electron localization function (ELF) are established for both LS and HS forms, leading to characterizion of the compound as an insulator in both spin states with larger gaps for LS configuration, while keeping molecular features in the solid. In [Fe(PM-BiA)₂(NCS)₂], by combining DFT and classical molecular dynamics, the properties and the domains of existence of the different phases are obtained by expressing the potential energy surfaces in a short range potential for Fe–N interactions. Applying such Fe–N potentials inserted in a classical force field and carrying out molecular dynamics (MD) in so-called “semi-classical MD” calculations, lead to the relative energies of HS/LS configurations of the crystal and to the assessment of the experimental (P, T) phase diagram. Full article

(This article belongs to the Special Issue Chemical Bond and Bonding 2015)

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16 pages, 3861 KiB

Open AccessArticle

Experimental and Theoretical Study of O-Substituent Effect on the Fluorescence of 8-Hydroxyquinoline

by Mohie E. M. Zayed, Reda M. El-Shishtawy, Shaaban A. Elroby, Abdullah Y. Obaid and Zahra M. Al-amshany

Int. J. Mol. Sci. 2015, 16(2), 3804-3819; https://doi.org/10.3390/ijms16023804 - 10 Feb 2015

Cited by 5 | Viewed by 11017

Abstract

The synthesis and characterization of different ether and ester derivatives of 8-hydroxyquinoline have been made. UV-visible and fluorescence spectra of these compounds have revealed spectral dependence on both solvent and O-substituent. The fluorescence intensity of ether derivatives revealed higher intensity for 8-octyloxyquinoline compared [...] Read more.

The synthesis and characterization of different ether and ester derivatives of 8-hydroxyquinoline have been made. UV-visible and fluorescence spectra of these compounds have revealed spectral dependence on both solvent and O-substituent. The fluorescence intensity of ether derivatives revealed higher intensity for 8-octyloxyquinoline compared with 8-methoxyquinoline, whereas those of ester derivatives had less fluorescence than 8-hydroxyquinoline. Theoretical calculations based on Time-dependent density functional theory (TD-DFT) were carried out for the quinolin-8-yl benzoate (8-OateQ) compound to understand the effect of O-substituent on the electronic absorption of 8-hydroxyquinaline (8-HQ). The calculations revealed comparable results with those obtained from the experimental data. Optimized geometrical structure was calculated with DFT at B3LYP/6-311++G** level of theory. The results indicated that 8-OateQ is not a coplanar structure. The absorption spectra of the compound were computed in gas-phase and solvent using B3LYP and CAM-B3LYP methods with 6-311++G ** basis set. The agreement between calculated and experimental wavelengths was very good at CAM-B3LYP/6-311++G** level of theory. Full article

(This article belongs to the Special Issue Chemical Bond and Bonding 2015)

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14 pages, 1096 KiB

Open AccessArticle

Acetic Acid Can Catalyze Succinimide Formation from Aspartic Acid Residues by a Concerted Bond Reorganization Mechanism: A Computational Study

by Ohgi Takahashi, Ryota Kirikoshi and Noriyoshi Manabe

Int. J. Mol. Sci. 2015, 16(1), 1613-1626; https://doi.org/10.3390/ijms16011613 - 12 Jan 2015

Cited by 17 | Viewed by 9913

Abstract

Succinimide formation from aspartic acid (Asp) residues is a concern in the formulation of protein drugs. Based on density functional theory calculations using Ace-Asp-Nme (Ace = acetyl, Nme = NHMe) as a model compound, we propose the possibility that acetic acid (AA), which [...] Read more.

Succinimide formation from aspartic acid (Asp) residues is a concern in the formulation of protein drugs. Based on density functional theory calculations using Ace-Asp-Nme (Ace = acetyl, Nme = NHMe) as a model compound, we propose the possibility that acetic acid (AA), which is often used in protein drug formulation for mildly acidic buffer solutions, catalyzes the succinimide formation from Asp residues by acting as a proton-transfer mediator. The proposed mechanism comprises two steps: cyclization (intramolecular addition) to form a gem-diol tetrahedral intermediate and dehydration of the intermediate. Both steps are catalyzed by an AA molecule, and the first step was predicted to be rate-determining. The cyclization results from a bond formation between the amide nitrogen on the C-terminal side and the side-chain carboxyl carbon, which is part of an extensive bond reorganization (formation and breaking of single bonds and the interchange of single and double bonds) occurring concertedly in a cyclic structure formed by the amide NH bond, the AA molecule and the side-chain C=O group and involving a double proton transfer. The second step also involves an AA-mediated bond reorganization. Carboxylic acids other than AA are also expected to catalyze the succinimide formation by a similar mechanism. Full article

(This article belongs to the Special Issue Chemical Bond and Bonding 2015)

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19 pages, 915 KiB

Open AccessArticle

Excited States and Photodebromination of Selected Polybrominated Diphenyl Ethers: Computational and Quantitative Structure—Property Relationship Studies

by Jin Luo, Jiwei Hu, Xionghui Wei, Lingyun Li and Xianfei Huang

Int. J. Mol. Sci. 2015, 16(1), 1160-1178; https://doi.org/10.3390/ijms16011160 - 6 Jan 2015

Cited by 11 | Viewed by 7253

Abstract

This paper presents a density functional theory (DFT)/time-dependent DFT (TD-DFT) study on the lowest lying singlet and triplet excited states of 20 selected polybrominateddiphenyl ether (PBDE) congeners, with the solvation effect included in the calculations using the polarized continuum model (PCM). The results [...] Read more.

This paper presents a density functional theory (DFT)/time-dependent DFT (TD-DFT) study on the lowest lying singlet and triplet excited states of 20 selected polybrominateddiphenyl ether (PBDE) congeners, with the solvation effect included in the calculations using the polarized continuum model (PCM). The results obtained showed that for most of the brominated diphenyl ether (BDE) congeners, the lowest singlet excited state was initiated by the electron transfer from HOMO to LUMO, involving a π–σ* excitation. In triplet excited states, structure of the BDE congeners differed notably from that of the BDE ground states with one of the specific C–Br bonds bending off the aromatic plane. In addition, the partial least squares regression (PLSR), principal component analysis-multiple linear regression analysis (PCA-MLR), and back propagation artificial neural network (BP-ANN) approaches were employed for a quantitative structure-property relationship (QSPR) study. Based on the previously reported kinetic data for the debromination by ultraviolet (UV) and sunlight, obtained QSPR models exhibited a reasonable evaluation of the photodebromination reactivity even when the BDE congeners had same degree of bromination, albeit different patterns of bromination. Full article

(This article belongs to the Special Issue Chemical Bond and Bonding 2015)

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20 pages, 9564 KiB

Open AccessArticle

Structure–Biological Function Relationship Extended to Mitotic Arrest-Deficient 2-Like Protein Mad2 Native and Mutants-New Opportunity for Genetic Disorder Control

by Speranta Avram, Adina Milac, Maria Mernea, Dan Mihailescu, Mihai V. Putz and Catalin Buiu

Int. J. Mol. Sci. 2014, 15(11), 21381-21400; https://doi.org/10.3390/ijms151121381 - 18 Nov 2014

Cited by 4 | Viewed by 6202

Abstract

Overexpression of mitotic arrest-deficient proteins Mad1 and Mad2, two components of spindle assembly checkpoint, is a risk factor for chromosomal instability (CIN) and a trigger of many genetic disorders. Mad2 transition from inactive open (O-Mad2) to active closed (C-Mad2) conformations or Mad2 binding [...] Read more.

Overexpression of mitotic arrest-deficient proteins Mad1 and Mad2, two components of spindle assembly checkpoint, is a risk factor for chromosomal instability (CIN) and a trigger of many genetic disorders. Mad2 transition from inactive open (O-Mad2) to active closed (C-Mad2) conformations or Mad2 binding to specific partners (cell-division cycle protein 20 (Cdc20) or Mad1) were targets of previous pharmacogenomics studies. Here, Mad2 binding to Cdc20 and the interconversion rate from open to closed Mad2 were predicted and the molecular features with a critical contribution to these processes were determined by extending the quantitative structure-activity relationship (QSAR) method to large-size proteins such as Mad2. QSAR models were built based on available published data on 23 Mad2 mutants inducing CIN-related functional changes. The most relevant descriptors identified for predicting Mad2 native and mutants action mechanism and their involvement in genetic disorders are the steric (van der Waals area and solvent accessible area and their subdivided) and energetic van der Waals energy descriptors. The reliability of our QSAR models is indicated by significant values of statistical coefficients: Cross-validated correlation q² (0.53–0.65) and fitted correlation r² (0.82–0.90). Moreover, based on established QSAR equations, we rationally design and analyze nine de novo Mad2 mutants as possible promoters of CIN. Full article

(This article belongs to the Special Issue Chemical Bond and Bonding 2015)

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21 pages, 527 KiB

Open AccessArticle

3D QSAR Studies, Pharmacophore Modeling and Virtual Screening on a Series of Steroidal Aromatase Inhibitors

by Huiding Xie, Kaixiong Qiu and Xiaoguang Xie

Int. J. Mol. Sci. 2014, 15(11), 20927-20947; https://doi.org/10.3390/ijms151120927 - 14 Nov 2014

Cited by 23 | Viewed by 7105 | Correction

Abstract

Aromatase inhibitors are the most important targets in treatment of estrogen-dependent cancers. In order to search for potent steroidal aromatase inhibitors (SAIs) with lower side effects and overcome cellular resistance, comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were [...] Read more.

Aromatase inhibitors are the most important targets in treatment of estrogen-dependent cancers. In order to search for potent steroidal aromatase inhibitors (SAIs) with lower side effects and overcome cellular resistance, comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were performed on a series of SAIs to build 3D QSAR models. The reliable and predictive CoMFA and CoMSIA models were obtained with statistical results (CoMFA: q² = 0.636, r²_ncv = 0.988, r²_pred = 0.658; CoMSIA: q² = 0.843, r²_ncv = 0.989, r²_pred = 0.601). This 3D QSAR approach provides significant insights that can be used to develop novel and potent SAIs. In addition, Genetic algorithm with linear assignment of hypermolecular alignment of database (GALAHAD) was used to derive 3D pharmacophore models. The selected pharmacophore model contains two acceptor atoms and four hydrophobic centers, which was used as a 3D query for virtual screening against NCI2000 database. Six hit compounds were obtained and their biological activities were further predicted by the CoMFA and CoMSIA models, which are expected to design potent and novel SAIs. Full article

(This article belongs to the Special Issue Chemical Bond and Bonding 2015)

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21 pages, 905 KiB

Open AccessArticle

Deactivation of 6-Aminocoumarin Intramolecular Charge Transfer Excited State through Hydrogen Bonding

by Ewa Krystkowiak, Krzysztof Dobek and Andrzej Maciejewski

Int. J. Mol. Sci. 2014, 15(9), 16628-16648; https://doi.org/10.3390/ijms150916628 - 19 Sep 2014

Cited by 10 | Viewed by 7406

Abstract

This paper presents results of the spectral (absorption and emission) and photophysical study of 6-aminocoumarin (6AC) in various aprotic hydrogen-bond forming solvents. It was established that solvent polarity as well as hydrogen-bonding ability influence solute properties. The hydrogen-bonding interactions between S₁-electronic [...] Read more.

This paper presents results of the spectral (absorption and emission) and photophysical study of 6-aminocoumarin (6AC) in various aprotic hydrogen-bond forming solvents. It was established that solvent polarity as well as hydrogen-bonding ability influence solute properties. The hydrogen-bonding interactions between S₁-electronic excited solute and solvent molecules were found to facilitate the nonradiative deactivation processes. The energy-gap dependence on radiationless deactivation in aprotic solvents was found to be similar to that in protic solvents. Full article

(This article belongs to the Special Issue Chemical Bond and Bonding 2015)

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Review

Jump to: Research

72 pages, 992 KiB

Open AccessReview

Competing Intramolecular vs. Intermolecular Hydrogen Bonds in Solution

by Peter I. Nagy

Int. J. Mol. Sci. 2014, 15(11), 19562-19633; https://doi.org/10.3390/ijms151119562 - 28 Oct 2014

Cited by 150 | Viewed by 17488

Abstract

A hydrogen bond for a local-minimum-energy structure can be identified according to the definition of the International Union of Pure and Applied Chemistry (IUPAC recommendation 2011) or by finding a special bond critical point on the density map of the structure in the [...] Read more.

A hydrogen bond for a local-minimum-energy structure can be identified according to the definition of the International Union of Pure and Applied Chemistry (IUPAC recommendation 2011) or by finding a special bond critical point on the density map of the structure in the framework of the atoms-in-molecules theory. Nonetheless, a given structural conformation may be simply favored by electrostatic interactions. The present review surveys the in-solution competition of the conformations with intramolecular vs. intermolecular hydrogen bonds for different types of small organic molecules. In their most stable gas-phase structure, an intramolecular hydrogen bond is possible. In a protic solution, the intramolecular hydrogen bond may disrupt in favor of two solute-solvent intermolecular hydrogen bonds. The balance of the increased internal energy and the stabilizing effect of the solute-solvent interactions regulates the new conformer composition in the liquid phase. The review additionally considers the solvent effects on the stability of simple dimeric systems as revealed from molecular dynamics simulations or on the basis of the calculated potential of mean force curves. Finally, studies of the solvent effects on the type of the intermolecular hydrogen bond (neutral or ionic) in acid-base complexes have been surveyed. Full article

(This article belongs to the Special Issue Chemical Bond and Bonding 2015)

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23 pages, 761 KiB

Open AccessReview

Influence of Sulfur for Oxygen Substitution in the Solvolytic Reactions of Chloroformate Esters and Related Compounds

by Malcolm J. D'Souza and Dennis N. Kevill

Int. J. Mol. Sci. 2014, 15(10), 18310-18332; https://doi.org/10.3390/ijms151018310 - 10 Oct 2014

Cited by 7 | Viewed by 9024

Abstract

The replacement of oxygen within a chloroformate ester (ROCOCl) by sulfur can lead to a chlorothioformate (RSCOCl), a chlorothionoformate (ROCSCl), or a chlorodithioformate (RSCSCl). Phenyl chloroformate (PhOCOCl) reacts over the full range of solvents usually included in Grunwald-Winstein equation studies of solvolysis by [...] Read more.

The replacement of oxygen within a chloroformate ester (ROCOCl) by sulfur can lead to a chlorothioformate (RSCOCl), a chlorothionoformate (ROCSCl), or a chlorodithioformate (RSCSCl). Phenyl chloroformate (PhOCOCl) reacts over the full range of solvents usually included in Grunwald-Winstein equation studies of solvolysis by an addition-elimination (A-E) pathway. At the other extreme, phenyl chlorodithioformate (PhSCSCl) reacts across the range by an ionization pathway. The phenyl chlorothioformate (PhSCOCl) and phenyl chlorothionoformate (PhOCSCl) react at remarkably similar rates in a given solvent and there is a dichotomy of behavior with the A-E pathway favored in solvents such as ethanol-water and the ionization mechanism favored in aqueous solvents rich in fluoroalcohol. Alkyl esters behave similarly but with increased tendency to ionization as the alkyl group goes from 1° to 2° to 3°. N,N-Disubstituted carbamoyl halides favor the ionization pathway as do also the considerably faster reacting thiocarbamoyl chlorides. The tendency towards ionization increases as, within the three contributing structures of the resonance hybrid for the formed cation, the atoms carrying positive charge (other than the central carbon) change from oxygen to sulfur to nitrogen, consistent with the relative stabilities of species with positive charge on these atoms. Full article

(This article belongs to the Special Issue Chemical Bond and Bonding 2015)

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