Utilizing first-principles calculations, we studied the electronic and optical properties of C24, C12X6Y6, and X12Y12 fullerenes (X?=?B, Al; Y?=?N, P). These fullerenes are energetically stable, as demonstrated by their negative cohesive energies. The energy gap of C24 may be tuned by doping, and the B12N12 fullerene was found to have the largest energy gap. All of the fullerenes had finite optical gaps, suggesting that they are optical semiconductors, and they strongly absorb UV radiation, so they could be used in UV light protection devices. They could also be used in solar cells and LEDs due to their low reflectivities.
Similar to σ-hole interactions, the π-hole interaction has attracted much attention in recent years. According to the positive electrostatic potentials above and below the surface of inorganic heterocyclic compounds S2N2 and three SN2P2 isomers (heterocyclic compounds 1–4), and the negative electrostatic potential outside the X atom of XH3 (X = N, P, As), S2N2/SN2P2?XH3 (X = N, P, As) complexes were constructed and optimized at the MP2/aug-cc-pVTZ level. The X atom of XH3 (X = N, P, As) is almost perpendicular to the ring of the heterocyclic compounds. The π-hole interaction energy becomes greater as the trend goes from 1?XH3 to 4?XH3. These π-hole interactions are weak and belong to “closed-shell” noncovalent interactions. According to the energy decomposition analysis, of the three attractive terms, the dispersion energy contributes more than the electrostatic energy. The polarization effect also plays an important role in the formation of π-hole complexes, with the contrasting phenomena of decreasing electronic density in the π-hole region and increasing electric density outside the X atom of XH3 (X = N, P, As).
Graphical abstract Computed density difference plots for the complexes 3?NH 3 (a 1), 3?PH 3 (b 1), 3?AsH 3 (c 1) and electron density shifts for the complexes 3?NH 3 (a 2), 3?PH 3 (b 2),3?AsH 3 (c 2) on the 0.001 a.u. contour
THE urate-binding α1–α2 globulin has been isolated from human plasma in a highly purified state1. The protein was purified by DEAE-‘Sephadex’, ammonium sulphate precipitation and semi-preparative Polyacrylamide gel electrophoresis. The urate-binding α1–α2 globulin is a rod-shaped glycoprotein, containing 12.1% carbohydrate, with an isoelectric point of 4.6 and a molecular weight of 67,000 ± 4,000. Amino-acid analysis indicated an unknown basic compound which appeared as an extra peak just in front of lysine1. To identify this compound, high voltage paper electrophoresis has been carried out on a plate electrophoresis apparatus in pyridine-acetate buffer pH 3.5. A spot separated out corresponding to ornithine. Amino-acid analysis on a BC-200 automatic analyser (Bio-Cal Instruments Co., West Germany), with a 54 cm column at 55° C and with 0.35 M sodium citrate buffer, pH 5.28, as elution buffer at a flow-rate of 150 ml./h, showed that ornithine was present. The presence of ornithine in the protein hydrolysate was also verified by gas chromatography/mass spectrometry2. 相似文献
Different subtypes of opioid receptors (OR) were activated in rats in vivo to study the activation effect on the heart’s resistance to ischemia and reperfusion. It has been established that administration of deltorphin II, a selective δ2-OR agonist, lowered the infarct size/area at risk index (IS/AAR) by 23%. Naltrexone, naloxone methiodide (an OR inhibitor not penetrating the blood-brain barrier (BBB)), and naltriben (δ2-antagonist) eliminated the cardioprotective effect of deltorphin II, while BNTX (a δ1-antagonist) produced no effect on the cardioprotective action of the δ2-agonist. The infarct-reducing effect of deltorphin II was eliminated by administration of chelerythrine (a protein kinase C (PKC) inhibitor), glibenclamide (a KATP-channels inhibitor), and 5-hydroxydecanoate (a mitochondrial KATP-channel blocker). Administration of other opioids did not reduce the IS/AAR index. It has been established that all the deltorphins manifest antiarrhythmic potency. Other opioids do not produce any effect on the incidence of arrhythmia occurrences. The antiarrhythmic effect of deltorphin II was eliminated by preliminary administration of naltrexone, naloxone methiodide, and naltriben, but BNTX did not affect the δ2-agonist’s anti-arrhythmic effect. The preliminary administration of chelerythrine, a PKC inhibitor, eliminated the δ2 agonist’s antiarrhythmic action. However, glibenclamide and 5-hydroxydecanoate did not alter the antiarrhythmic effect by deltorphin II. Therefore, activation of the peripheral δ2-ORs reduces the infarct size and prevents the onset of arrhythmias. The antiarrhythmic effect of the δ2-OR stimulation is mediated by activating PKC and opening the mitochondrial KATP-channels. PKC participates in the antiarrhythmic effect of the δ2-OR activation, but this effect does not depend on the condition of KATP-channels. 相似文献
While ~30% of the human genome encodes membrane proteins, only a handful of structures of membrane proteins have been resolved to high resolution. Here, we studied the structure of a member of the Cys-loop ligand gated ion channel protein superfamily of receptors, human type A γ2α1β2α1β2 gamma amino butyric acid receptor complex in a lipid bilayer environment. Studying the correlation between the structure and function of the gamma amino butyric acid receptor may enhance our understanding of the molecular basis of ion channel dysfunctions linked with epilepsy, ataxia, migraine, schizophrenia and other neurodegenerative diseases. The structure of human γ2α1β2α1β2 has been modeled based on the X-ray structure of the Caenorhabditis elegans glutamate-gated chloride channel via homology modeling. The template provided the first inhibitory channel structure for the Cys-loop superfamily of ligand-gated ion channels. The only available template structure before this glutamate-gated chloride channel was a cation selective channel which had very low sequence identity with gamma aminobutyric acid receptor. Here, our aim was to study the effect of structural corrections originating from modeling on a more reliable template structure. The homology model was analyzed for structural properties via a 100 ns molecular dynamics (MD) study. Due to the structural shifts and the removal of an open channel potentiator molecule, ivermectin, from the template structure, helical packing changes were observed in the transmembrane segment. Namely removal of ivermectin molecule caused a closure around the Leu 9 position along the ion channel. In terms of the structural shifts, there are three potential disulfide bridges between the M1 and M3 helices of the γ2 and 2 α1 subunits in the model. The effect of these disulfide bridges was investigated via monitoring the differences in root mean square fluctuations (RMSF) of individual amino acids and principal component analysis of the MD trajectory of the two homology models—one with the disulfide bridge and one with protonated Cys residues. In all subunit types, RMSF of the transmembrane domain helices are reduced in the presence of disulfide bridges. Additionally, loop A, loop F and loop C fluctuations were affected in the extracellular domain. In cross-correlation analysis of the trajectory, the two model structures displayed different coupling in between the M2–M3 linker region, protruding from the membrane, and the β1-β2/D loop and cys-loop regions in the extracellular domain. Correlations of the C loop, which collapses directly over the bound ligand molecule, were also affected by differences in the packing of transmembrane helices. Finally, more localized correlations were observed in the transmembrane helices when disulfide bridges were present in the model. The differences observed in this study suggest that dynamic coupling at the interface of extracellular and ion channel domains differs from the coupling introduced by disulfide bridges in the transmembrane region. We hope that this hypothesis will be tested experimentally in the near future. 相似文献
Mitochondrial production of H2O2 is low with NAD substrates (glutamate/pyruvate, 3 and 2 mM) (G/P) and increases over ten times upon further addition of succinate,
with the formation of a sigmoidal curve (semimaximal value at 290 μM, maximal H2O2 production at 600 μM succinate). Malate counteracts rapidly the succinate induced increased H2O2 release and moves the succinate dependent H2O2 production curve to the right. Nitric oxide (NO) and carbon monoxide (CO) are cytochrome c oxidase inhibitors which increase
mitochondrial ROS production. Cyanide (CN−) was used to mimic NO and CO. In the presence of G/P and succinate (300 μM), CN− progressively increased the H2O2 release rate, starting at 1.5 μM. The succinate dependent H2O2 production curve was moved to the left by 30 μM CN−. The Vmax was little modified. We conclude that succinate is the controller of mitochondrial H2O2 production, modulated by malate and CN−. We propose that succinate promotes an interaction between Complex II and Complex I, which activates O2− production. 相似文献
In a quest to identify new ground-state triplet germylenes, the stabilities (singlet–triplet energy differences, ΔES–T) of 96 singlet (s) and triplet (t) M1-Ge-M2-M3 species were compared and contrasted at the B3LYP/6–311++G**, QCISD(T)/6–311++G**, and CCSD(T)/6–311++G** levels of theory (M1?=?H, Li, Na, K; M2?=?Be, Mg, Ca; M3?=?H, F, Cl, Br). Interestingly, F-substituent triplet germylenes (M3?=?F) appear to be more stable and linear than the corresponding Cl- or Br-substituent triplet germylenes (M3?=?Cl or Br). Triplets with M1?=?K (i.e., the K-Ge-M2-M3 series) seem to be more stable than the corresponding triplets with M1?=?H, Li, or Na. This can be attributed to the higher electropositivity of potassium. Triplet species with M3?=?Cl behave similarly to those with M3?=?Br. Conversely, triplets with M3?=?H show similar stabilities and linearities to those with M3?=?F. Singlet species of formulae K-Ge-Ca-Cl and K-Ge-Ca-Br form unexpected cyclic structures. Finally, the triplet germylenes M1-Ge-M2-M3 become more stable as the electropositivities of the α-substituents (M1 and M2) and the electronegativity of the β-substituent (M3) increase. 相似文献
Sodium Nitroprusside (SNP) and S-Nitrosoglutathione (GSNO) differently affect mitochondrial H2O2 release at Complex-I. mM SNP increases while GSNO decreases the release induced by succinate alone or added on top of NAD-linked
substrates. Stimulation likely depends on Nitric Oxide (.NO) (released by SNP but not by GSNO) inhibiting cytochrome oxidase and mitochondrial respiration. Preincubations with SNP
or high GSNO (10 mM plus DTE to increases its .NO release) induces an inhibition of the succinate dependent H2O2 production consistent with a .NO dependent covalent modification. However maximal inhibition of the succinate dependent H2O2 release is obtained in the presence of low GSNO (20–100 μM), but not with SNP. This inhibition appears independent of .NO release since μM GSNO does not affect mitochondrial respiration, or the H2O2 detection systems and its effect is very rapid. Inhibition may be partly due to an increased removal of O2.− since GSNO chemically competes with NBT and cytochrome C in O2.− detection. 相似文献
Nine minima were found on the intermolecular potential energy surface for the ternary system HNO3(CH3OH)2 at the MP2/aug-cc-pVDZ level of theory. The cooperative effect, which is a measure of the hydrogen-bonding strength, was probed in these nine conformations of HNO3…(CH3OH)2. The results are discussed here in terms of structures, energetics, infrared vibrational frequencies, and topological parameters. The cooperative effect was observed to be an important contributor to the total interaction energies of the cyclic conformers of HNO3…(CH3OH)2, meaning that it cannot be neglected in simulations in which the pair-additive potential is applied.
A new metal complex, Fe(Sal2dienNO3·H2O) (where Sal is salicylaldehyde and dien is diethylenetriamine), has been synthesized and characterized. The interactions
between the Fe(III) complex and calf thymus DNA has been investigated using UV and fluorescence spectra, viscosity, thermal
denaturation, and molecular modeling. The cleavage reaction on plasmid DNA has been monitored by agarose gel electrophoresis.
The experimental results show that the mode of binding of the complex to DNA is classical intercalation and the complex can
cleave pBR322 DNA. 相似文献
Ab initio calculations have been performed using the complete basis set model (CBS-QB3) to study the reaction mechanism of
butane radical (C4H9•) with oxygen (O2). On the calculated potential energy surface, the addition of O2 to C4H9• forms three intermediates barrierlessly, which can undergo subsequent isomerization or decomposition reaction leading to
various products: HOO• + C4H8, C2H5• + CH2CHOOH, OH• + C3H7CHO, OH• + cycle-C4H8O, CH3• + CH3CHCHOOH, CH2OOH• + C3H6. Five pathways are supposed in this study. After taking into account the reaction barrier and enthalpy, the most possible
reaction pathway is C4H9• + O2 → IM1 → TS5 → IM3 → TS6 → IM4 → TS7 → OH• + cycle-C4H8O. 相似文献
The 125I-labeled B-subunit of the cholera toxin ([125I]CT-B, specific activity of 98 Ci/mmol) was prepared. This subunit was shown to be bound to the membranes which were isolated from epithelial cells of a mucous tunic of the rat thin intestine with high affinity (Kd = 3.7 nM). The binding of the labeled protein was inhibited by the unlabeled α2-interferon (IFN-α2), α1-thymosin, (TM-α1), and the LKEKK synthetic peptide corresponding to the 16–20 sequence of TM-α1 and the 131–135 sequence of human IFN-α2 (Ki 1.0, 1.5, and 2.0 nM, respectively), whereas the KKEKL unlabeled synthetic peptide did not inhibit the binding (Ki > 100 μМ). The LKEKK peptide and CT-B were shown to dose-dependently increase an activity of the soluble guanylate cyclase (sGC) in the concentration range from 10 to 1000 nM. Thus, the binding of TM- α1, IFN-α2, and the LKEKK peptide to the CT-B receptor on a surface of the epithelial cells of the mucous tunic of the rat thin intestine resulted in an increase in the intracellular level of cGMP. 相似文献
The structures and stabilities of eleven N13+ and N13– isomers have been investigated with second-order Møller–Plesset (MP2) and density functional theory (DFT) methods. Five N13+ isomers and six N13– isomers are all reasonable local minima on their potential energy hypersurfaces. The most stable N13+ cation is structure C-2 with C2v symmetry, which contains a pentazole ring and two N4 open chains. It is different from those of the N7+ and N9+ clusters, but similar to the N11+ cluster. Meanwhile, the most stable N13– structure A-2 is composed of a pentazole ring and a six-membered ring connected by two nitrogen atoms. It is not only different from those of the N7– and N9– clusters, but also from the N11– cluster. The decomposition pathways of structures C-2 and A-2 were investigated at the B3LYP/(aug)-cc-pVDZ level. From the barrier heights of the structures C-2 and A-2 decomposition processes, it is suggested that C-2 is difficult to observe experimentally and A-2 may be observed as a short-lived species.
Figure Optimized geometrical parameters of N13+ isomer C-2相似文献
The nature of M–M bonding and aromaticity of [M2(NHCHNH)3]2(μ-E)2 (E?=?O, S; M?=?Nb, Mo, Tc, Ru, Rh) was investigated using atoms in molecules (AIM) theory, electron localization function (ELF), natural bond orbital (NBO) and molecular orbital analysis. These analyses led to the following main conclusions: in [M2(NHCHNH)3]2(μ-E)2 (E?=?O, S; M?=?Nb, Mo, Tc, Ru, Rh), the Nb–Nb, Ru–Ru, and Rh–Rh bonds belong to “metallic” bonds, whereas Mo–Mo and Tc–Tc drifted toward the “dative” side; all these bonds are partially covalent in character. The Nb–Nb, Mo–Mo, and Tc–Tc bonds are stronger than Ru–Ru and Rh–Rh bonds. The M–M bonds in [M2(NHCHNH)3]2(μ-S)2 are stronger than those in [M2(NHCHNH)3]2(μ-O)2 for M?=?Nb, Mo, Tc, and Ru. The NICS(1)ZZ values show that all of the studied molecules, except [Ru2(NHCHNH)3]2(μ-O)2, are aromaticity molecules. O-bridged compounds have more aromaticity than S-bridged compounds.
Graphical AbstractLeft Molecular graph, and right electron localization function (ELF) isosurface of [M2(NHCHNH)3]2(μ-E)2(E?=?O, S; M?=?Nb, Mo, Tc, Ru, Rh)
Ab initio (RHF, MP2) and Density Functional Theory (DFT) methods have been used to examine six isomers of the N15m cluster with the 6-31+G* basis set. Different from the known odd-numbered anionic N7m, N9m, and N11m clusters, in which the open-chain structures are the most stable species, the most stable N15m isomer is structure 1 (C1), which may be considered as a complex between the fragments cyclic N5m (D5h) and staggered N10 (D2d). The decomposition pathways of structure 2 (CS), containing two aromatic N5 rings connected by a N5 chain, and the open-chain structure 3 (C2v) were studied at the B3LYP/6-31+G* level of theory. Relative energies were refined at the level of B3LYP/6-311+G(3df,2p)//B3LYP/6-31+G*+ZPE (B3LYP/6-31+G*). The barriers for N2 and N5m (D5h) fission reactions for structure 2 are predicted to be 18.2 and 14.2 kcal x mol(-1), respectively. The corresponding N2+N3m fission barrier for structure 3 is predicted to be 11.2 kcal x mol(-1). Supplementary material is available for this article if you access the article at http://dx.doi.org/10.1007/s00894-003-0118-0. A link in the frame on the left on that page takes you directly to the supplementary material. Figure Structure 1 of the N15m cluster, showing bond distances in A and bond angles in degrees 相似文献
MHC class I molecules are heterotrimeric complexes composed of heavy chain, 2-microglobulin (2m) and short peptide. This trimeric complex is generated in the endoplasmic reticulum (ER), where a peptide loading complex (PLC) facilitates transport from the cytosol and binding of the peptide to the preassembled ER resident heavy chain/2m dimers. Association of mouse MHC class I heavy chain with 2m is characterized by allelic differences in the number and/or positions of amino acid interactions. It is unclear, however, whether all alleles follow common binding patterns with minimal contributions by allele-specific contacts, or whether essential contacts with 2m are different for each allele. While searching for the PLC binding site in the 3 domain of the mouse MHC class I molecule H-2Db, we unexpectedly discovered a site critical for binding mouse, but not human, 2m. Interestingly, amino acids in the corresponding region of another MHC class I heavy chain allele do not make contacts with the mouse 2m. Thus, there are allelic differences in the modes of binding of 2m to the heavy chain of MHC class I. 相似文献
The molecular geometries, vibrational properties, and thermodynamic properties of the clusters (Br2GaN3)n(n = 1–4) were studied at the B3LYP/6-311+G* level. The optimized clusters (Br2GaN3)n(n = 2–4) were all found to possess a cyclic structure consisting of Ga atoms bridged by the α-nitrogen of the azide groups.
A discussion of the relationships between the geometrical parameters and the degree of oligomerization n is provided. Features in the IR spectra were assigned by vibrational analysis. Trends in thermodynamic properties with temperature
and degree of oligomerization n are discussed. Thermodynamic analysis of the gas-phase reaction showed that the formation of the clusters (Br2GaN3)n(n = 2–4) is thermodynamically favorable considering the enthalpies at 298.2 K. The calculated results for the Gibbs free energies
were negative, which indicates that the oligomerizations can occur spontaneously at 298.2 K. 相似文献
Summary Phosphatidylinositol 3-kinase (PI3K) pathway is important for platelet activation. Recent studies showed that PI3K and oscillative
calcium could cross talk to each other and positively regulate integrin α IIbβ3-mediated outside-in signaling. However, the mechanism of this feedback regulation remains to be further characterized. Here
we found that treatments of both PI3K inhibitor wortmannin and P2Y1 inhibitor A3P5P could inhibit granular secretion in platelets.
Additionally, when RGD-substrate adherent platelets were treated with the ADP scavenger apyrase to deplete the granular-released
ADP, their attachments in engaging with substrates became looser and the frequency of calcium oscillation decreased. Since
it is known that ADP stimulates the PI3K and calcium signal primarily through P2Y12 and P2Y1 receptors respectively, our data
indicated that integrin αIIbβ3 downstream PI3K and calcium activation might be not completely coupled to integrin associated signaling complex, but in part
through feedback stimulation by granular released ADP. Our data indicates the important roles of PI3K and granular released
ADP in coordinating the feedback regulations in integrin αIIbβ3-mediated platelet activation. 相似文献
Molecular docking simulations were performed in this study to investigate the importance of both structural and catalytic zinc ions in the human alcohol dehydrogenase beta(2)beta(2) on substrate binding. The structural zinc ion is not only important in maintaining the structural integrity of the enzyme, but also plays an important role in determining substrate binding. The replacement of the catalytic zinc ion or both catalytic and structural zinc ions with Cu(2+) results in better substrate binding affinity than with the wild-type enzyme. The width of the bottleneck formed by L116 and V294 in the substrate binding pocket plays an important role for substrate entrance. In addition, unfavorable contacts between the substrate and T48 and F93 prevent the substrate from moving too close to the metal ion. The optimal binding position occurs between 1.9 and 2.4 A from the catalytic metal ion. 相似文献
