Hydrogen bonds determine the structures of the ternary heterocyclic complexes C₂H₄O···2HF, C₂H₅N···2HF and C₂H₄S···2HF: density functional theory and topological calculations

A theoretical study of structural, electronic, topological and vibrational parameters of the ternary hydrogen-bonded complexes C₂H₄O···2HF, C₂H₅N···2HF and C₂H₄S···2HF is presented here. Different from binary systems with a single proton donor, the tricomplexes have the property of forming multiple hydrogen bonds, which are analyzed from a structural and vibrational point of view, but verified only by means of the quantum theory of atoms in molecules (QTAIM). As traditionally done in the hydrogen bond theory, the charge transfer between proton donors and acceptors was computed using the CHELPG calculations, which also revealed agreement with dipole moment variation and a cooperative effect on the tricomplexes. Furthermore, redshift events on proton donor bonds were satisfactorily identified, although, in this case, an absence of experimental data led to the use of a theoretical argument to interpret these spectroscopic shifts. It was therefore the use of the QTAIM parameters that enabled all intermolecular vibrational modes to be validated. The most stable tricomplex in terms of energy was identified via the strength of the hydrogen bonds, which were modeled as directional and bifurcated.     

Double coned inverse sandwich complexes [M-(η4-C4H4)-M′] of Gr-IA and Gr-IIA Metals: theoretical study of electronic of structure and second hyperpolarizability

Molecular interaction between dioxane and methanol involves certain polar and nonpolar bonding to form a one to one complex. Interatomic distances between hydrogen and oxygen within 3 Å have been considered as hydrogen bonding. Optimizations of the structures of dioxane-methanol complexes were carried out considering any spatial orientation of a methanol molecule around a chair/boat/twisted-boat conformation of dioxane. From 45 different orientations of dioxane and water, 23 different structures with different local minima were obtained and the structural characteristics like interatomic distances, bond angles, dihedral angles, dipole moment of each complex were discussed. The most stable structure, i.e., with minimum heat of formation is found to have a chair form dioxane, one O-H…O, and two C-H…O hydrogen bonds. In general, the O-H…O hydrogen bonds have an average distance of 1.8 Å while C-H…O bonds have 2.6 Å. The binding energy of the dioxane-methanol complex is found to be a linear function of number of O-H…O and C-H…O bonds, and hydrogen bond length. Graphical Abstract

Sixteen orientations of methanol around dioxane converge to six local minima including the global minima with one H-O…H and two C-H…O hydrogen bonds.     

The effect of a Pro²⁸Thr point mutation on the local structure and stability of human galactokinase enzyme-a theoretical study

Galactokinase is responsible for the phosphorylation of α-d-galactose, which is an important step in the metabolism of the latter. Malfunctioning of galactokinase due to a single point mutation causes cataracts and, in serious cases, blindness. This paper reports a study of the Pro²⁸Thr point mutation using a variety of theories including molecular dynamics (MD), MM-PBSA/GBSA calculations and AIM analysis. Altered H-bonding networks were detected based on geometric and electron density criteria that resulted in local unfolding of the β-sheet secondary structure. Another consequence was the decrease in stability (5–7 kcal mol⁻¹) around this region, as confirmed by ΔG_bind calculations for the extracted part of the whole system. Local unfolding was verified by several other MD simulations performed with different duration, initial velocities and force field. Based on the results, we propose a possible mechanism for the unfolding caused by the Pro²⁸Thr point mutation.     

Opposing roles of H3- and H4-acetylation in the regulation of nucleosome structure—a FRET study

Using FRET in bulk and on single molecules, we assessed the structural role of histone acetylation in nucleosomes reconstituted on the 170 bp long Widom 601 sequence. We followed salt-induced nucleosome disassembly, using donor–acceptor pairs on the ends or in the internal part of the nucleosomal DNA, and on H2B histone for measuring H2A/H2B dimer exchange. This allowed us to distinguish the influence of acetylation on salt-induced DNA unwrapping at the entry–exit site from its effect on nucleosome core dissociation. The effect of lysine acetylation is not simply cumulative, but showed distinct histone-specificity. Both H3- and H4-acetylation enhance DNA unwrapping above physiological ionic strength; however, while H3-acetylation renders the nucleosome core more sensitive to salt-induced dissociation and to dimer exchange, H4-acetylation counteracts these effects. Thus, our data suggest, that H3- and H4-acetylation have partially opposing roles in regulating nucleosome architecture and that distinct aspects of nucleosome dynamics might be independently controlled by individual histones.     

The structure and properties of tetrakis(tironato)cerate(IV), Na12[Ce(C6H2O2(SO3)2)4]·9H2O·6C3H7NO

The title complex, prepared in 1 M NaOH, was crystallized from hot N,N-dimethylformamide/ ethanol solutions to give Na₁₂[Ce(C₆H₂O₂(SO₃)₂)₄]· 9H₂O·6DMF. The purple—brown crystals were examined by X-ray diffraction while inside quartz capillaries filled with DMF, (λ_max 425 nm, ϵ 3664; λ_sh 520 nm, ϵ 2240) and belong to space group Pbca, Z=8 with a=21.846(4), b=17.348(2), c=43.103- (6) Å, V=16.335(7) ų, D_c=1.693 gcm^t−3, D_o=1.725 g cm^t−3. Diffractometer data were collected using Mo Kα radiation to 2θ=43^o. For 7331 independent data with F_o²>3σ(F_o²) full matrix least squares refinement converged to unweighted and weighted R factors of 0.072 and 0.110, respectively, with a mixture of anisotropic and isotropic thermal parameters. The disordered DMF atom parameters were not refined. The structure consists of discrete monomeric Ce(C₆H₂S₂O₈)₄¹²⁻ units with 12 Na⁺ counter cations and 10 H₂O molecules (two with half occupancy), and 6 DMF molecules of solvation filling up spaces between cations and anions. Cerium(IV) is in a general position with a coordination polyhedron close to the trigonal-faced dodecahedron, D_2d, with the angles between the two BAAB trapezoids of 2.3^o and 3.7^o. The average CeO(A) distance, 2.363(9) Å is longer than the average CeO(B) distance, 2.326(15)Å, with the reverse being true for one of the four tironato ligands. The average ring OCeO angle is 67.9(1)^o. The cerium (IV) complex is found by cyclic voltammetry to undergo a quasi-reversible one-electron reduction (in strongly basic solution with excess tiron) with Ef=−497 mV vs. SCE, hence the ratio of the formation constants for tetrakis(tironato)cerate(IV) to that for tetrakis(tironato)cerate(III), K_IV/K_III, is 10³³. Characterization of other tiron salts is reported.     

Influence of HOCl…O3 and HOCl…HOCl interactions on the stability of O3(HOCl)2 complexes: a theoretical study

We have analysed the role of HOCl…O₃ and HOCl…HOCl interactions on the stability of four estimated O₃(HOCl)₂ complexes by means of ab initio molecular orbital calculations. It is predicted that the O₃(HOCl) + HOCl reaction is more energetically favourable than (HOCl)₂ + O₃ one. In all complexes, HOCl…HOCl interaction is stronger than HOCl…O₃ one. The results show that the HOCl…O₃ interaction strengthens the HOCl…HOCl one. On the other hand, O…H interaction in HOCl…O₃ moiety is strengthened when it interacts with HOCl. Quantum theory of atoms in molecules predicts that the weak interactions in O₃(HOCl)₂ complexes have electrostatic characteristic. In all complexes, the charge transfer from O₃ to (HOCl)₂ is expected from natural bond orbital analysis.     

Insights into the crystal structure of BRD2-BD2 – phenanthridinone complex and theoretical studies on phenanthridinone analogs

Bromodomain and extra-terminal family proteins recognize the acetylated histone code on chromatin and participate in downstream processes like DNA replication, modification, and repair. As part of epigenetic approaches, BRD2 and BRD4 were identified as putative targets, for the management of chronic diseases. We have recently reported the discovery of a new scaffold of the phenanthridinone-based inhibitor (L10) of the second bromodomain of BRD2 (BRD2-BD2). Here, we present the crystal structure of the BRD2-BD2, refined to 1.4 Å resolution, in complex with β-mercaptoethanol (a component of the protein buffer). The β-mercaptoethanol covalently links to C425 of BD2 in the acetyl-lysine binding pocket, to form a modified cysteine mercaptoethanol (CME). The CME modification significantly hinders the entry of ligands into the BD2 binding pocket, suggesting that β-mercaptoethanol should be removed during protein production process. Next, to confirm whether phenanthridionone scaffold is a new inhibitor family of BRD2-BD2, we have determined the crystal structure of BD2 in complex with 6(5H)-Phenanthridinone (a core moiety of L10), refined to 1.28 Å resolution. It confirmed that the phenanthridinone molecule, unambiguously, binds to BD2. Moreover, we performed molecular docking and molecular dynamic studies on selected phenanthridinone analogs. The predicted L10 analogs are stable with essential hydrophobic and hydrophilic interactions with BD2 during molecular dynamic simulations. We propose that the predicted phenanthridinone analogs may be potential molecules for inhibiting the BD2 function of acetylated histone recognition.     

The synaptonemal complex: a structure necessary for pairing, recombination or organization of the meiotic chromosome?

The synaptonemal complex (SC) is a prominent and evolutionaly well conserved structure which is strictly meiotic. Several evidences from mutant phenotypes support the hypothesis that recombination and SC formation are mutually interdependent processes. Moreover, the SC recombination nodules correspond in number and location to the crossing-over events. However, recent data confirm that SC formation does not require initiation of recombination, and several observations indicate that full synapsis is not required for recombination. The potential roles played by the SC will be discussed in the following framework: First, although not required for homology recognition, the SC could promote interhomolog interactions in situations where the normal processes have failed (interlocking, heterologous pairing, etc.); Second, polymerization of the SC components might permit the recombination process to progress by modulating the number and localisation of reciprocal versus nonreciprocal exchanges (i.e. interference) and; Third, the SC may play an important role in meiotic chromosome structure and especially in inter-sister interactions.     

A chemometrical study of intermolecular properties of hydrogen-bonded complexes formed by C2H4O⋅⋅⋅HX and C2H5N⋅⋅⋅HX with X = F, CN, NC, and CCH

We presents a chemometrical study of the intermolecular properties of the C₂H₄O⋅⋅⋅HX and C₂H₅N⋅⋅⋅HX hydrogen-bonded complexes with X = F, CN, NC, and CCH. Through the MP2 perturbation theory and B3LYP hybrid functional, as well as modifications on 6-31ijGk basis sets with i = triple-zeta, j = diffuse and k = polarization functions, systematic tendencies in the R_{(n⋅⋅⋅HX)} hydrogen bond distances and υ_{(n⋅⋅⋅HX)} stretch frequencies were determined by the hierarchical cluster analysis, two level factorial designs and principal component analysis. Based on well-fitted math models, not only because polarization functions provide a great variance on statistical analysis, but this basis set reproduces more efficiently the available experimental results. Moreover, independent of whether the quality on basis set is increased, the effects yielded by both DFT and MP2 were not considered important in the statistical analysis.     

Calcium complexation with a highly calcium selective chelator: crystal structure of ca(CaFBAPTA) ·5H2O

The structure of the complex of calcium ions with 5,5'-difluoro-1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (FBAPTA) has been determined. The calcium complex, with stoichiometry Ca(CaFBAPTA) · 5H₂O crystallizes in a monoclinic space group P2₁/c with 4 formula units/unit cell with a(Å) = 9.767, b(Å) = 26.309,c(Å) = 11.769; β (deg) = 111.57. The structure may be considered as the calcium salt of a CaFBAPTA2- complex in which the octacoordinate calcium ion is complexed with the two ether oxygen atoms, the two nitrogens, and coordinated in a unidentate manner with the four acetate carboxyl groups. The geometry of the nitrogen atoms is nearly tetrahedral and provides a basis for the interpretation of the optical perturbations which result from calcium complexation with BAPTA type ligands. In addition, it is clear from the distance and relative orientation of the aromatic rings that ring current contributions to the fluorine chemical shifts are of negligible importance, so that such effects cannot be used in the design of NMR active indictators. Although BAPTA and analogs such as PBAPTA and quin2 have found extensive physiological applications as a consequence of the high degree of selectivity for calcium ions over magnesium ions which they exhibit, this is the first reported structural data for any of these complexes.     

Resonance Raman studies of the peroxotitanate(IV) complexes K2(Ti(O2)(SO4)2)·5H2O and K2(Ti(O2)(C2O4)2)·3H2O

The resonance Raman spectra of K₂(Ti(O₂)(SO₄)₂)·5H₂O and K₂(Ti(O₂)(C₂O₄)₂)·3H₂O are recorded. The results are consistent with the triangular structure of the peroxotitanium unit, Ti(O₂), with C_2ν symmetry. The ν(OO), ν_s(TiO) and ν_as(TiO) are observed around 890, 610 and 535 cm⁻¹, respectively. The resonance effects are shown to be associated with the 425 nm absorption band. This band is assigned to the O₂²⁻ → Ti(IV) charge-transfer transition. The calculated force constant values for the O₂²⁻ and TiO bonds are 320 and 275 N m⁻¹, respectively.     

A model of O·2 - generation in the complex III of the electron transport chain

Oxidation of semiquinone by O₂ in the Q cycle is known to be one of the sources of superoxide anion (O·₂ ^-) in aerobic cells. In this paper, such a phenomenon was analyzed using the chemical kinetics model of electron transfer from succinate to cytochrome c, including coenzyme Q, the complex III non-heme iron protein FeS_III and cytochromes b₁, b_h and c₁. Electron transfers from QH₂ to FeS_III and cytochrome b₁ were assumed to occur according to direct transfer mechanism (dynamic channelling) involving the formation of FeS^red _III -Q·^- and Q·^--cytochrome b₁ complexes. For oxidation/reduction reactions involving cytochromes b_h and b₁, the dependence of the equilibrium and elementary rate constants on the membrane potential () was taken into consideration. The rate of O·₂ ^- generation was found to increase dramatically with increase in above the values found in State 3. On the other hand, the rate of cytochrome c reduction decreased sharply at the same values of the membrane potential. This explains experimental data that the O·2^- generation at State 4 appears to be very much faster than at State 3. A mild uncoupling in State 4 can markedly decrease the superoxide generation due to a decrease in below the above mentioned critical level. pH appears to be equally effective as in stimulation of superoxide production which depends, in fact, upon the ^- _H + level.     

The Electronic Structure and Chemicai Bonding of (η5 -C5H5)2LuCl·OC4H8: a localized INDO study

A localized INDO study revealed that the monomeric (η₅-C₅H₅)₂LuCl·OC₄H₈ is covalent in character. The main contribution of the metal to bonding is due to the 5d orbitals while the 4f orbitals are strongly localized. The stability of the monomer may be attributed to the great energy gap between the HOMO and the LUMO and the steric hindrance of the THF group. The possible dimerization of dicyclopentadienyl lanthanide chlorides and the complexing activation of LnCl bond are discussed.     

The Q-cycle reviewed: How well does a monomeric mechanism of the bc1 complex account for the function of a dimeric complex?

Recent progress in understanding the Q-cycle mechanism of the bc₁ complex is reviewed. The data strongly support a mechanism in which the Q_o-site operates through a reaction in which the first electron transfer from ubiquinol to the oxidized iron–sulfur protein is the rate-determining step for the overall process. The reaction involves a proton-coupled electron transfer down a hydrogen bond between the ubiquinol and a histidine ligand of the [2Fe–2S] cluster, in which the unfavorable protonic configuration contributes a substantial part of the activation barrier. The reaction is endergonic, and the products are an unstable ubisemiquinone at the Q_o-site, and the reduced iron–sulfur protein, the extrinsic mobile domain of which is now free to dissociate and move away from the site to deliver an electron to cyt c₁ and liberate the H⁺. When oxidation of the semiquinone is prevented, it participates in bypass reactions, including superoxide generation if O₂ is available. When the b-heme chain is available as an acceptor, the semiquinone is oxidized in a process in which the proton is passed to the glutamate of the conserved -PEWY- sequence, and the semiquinone anion passes its electron to heme b_L to form the product ubiquinone. The rate is rapid compared to the limiting reaction, and would require movement of the semiquinone closer to heme b_L to enhance the rate constant. The acceptor reactions at the Q_i-site are still controversial, but likely involve a “two-electron gate” in which a stable semiquinone stores an electron. Possible mechanisms to explain the cyt b₁₅₀ phenomenon are discussed, and the information from pulsed-EPR studies about the structure of the intermediate state is reviewed.The mechanism discussed is applicable to a monomeric bc₁ complex. We discuss evidence in the literature that has been interpreted as shown that the dimeric structure participates in a more complicated mechanism involving electron transfer across the dimer interface. We show from myxothiazol titrations and mutational analysis of Tyr-199, which is at the interface between monomers, that no such inter-monomer electron transfer is detected at the level of the b_L hemes. We show from analysis of strains with mutations at Asn-221 that there are coulombic interactions between the b-hemes in a monomer. The data can also be interpreted as showing similar coulombic interaction across the dimer interface, and we discuss mechanistic implications.