Quantum chemical study in the direction to design efficient donor-bridge-acceptor triphenylamine sensitizers with improved electron injection

The ground state geometries have been computed by using density functional theory. The excitation energies for dye sensitizers were performed by using time dependant density functional theory. The polarizable continuum model (PCM) has been used for evaluating bulk solvent effects at all stages. The calculations have been carried out in methanol according to the experimental set up. The long-range-corrected functional (PCM-TD-LC-BLYP) underestimate the absorption spectrum of parent molecule while PCM-TDBHandHLYP is in good agreement with the experimental data. The highest occupied molecular orbital (HOMO) is delocalized on TPA moiety while lowest unoccupied molecular orbital (LUMO) is localized on anchoring group, conjugated chain and the benzene ring near to the anchoring group. The LUMO energies of all the investigated dyes are above the conduction band of TiO(2), HOMOs are below the redox couple and HOMO-LUMO energy gaps of studied dyes are smaller compared to TC4. The 1 and 3 are 7 and 12?nm blue shifted while 2 and 4 are 25 and 22?nm red shifted, respectively compared to TC4. The trend of electron injection (ΔG(inject)), relative electron injection (ΔG (r) (inject) ()), and electronic coupling constant (|VRP|) has been observed as 3?>?1?>?4?>?2?>?TC4. The improved ΔG(inject), |VRP| and light harvesting efficiency (LHE) of new designed sensitizers revealed that these materials would be excellent sensitizers. The broken coplanarity between the benzene near anchoring group having LUMO and the last benzene attached to TPA unit in 1-4 consequently would hamper the recombination reaction.     

Cytotoxicity of N6-cycloalkylated adenine and adenosine analogs to mouse hepatoma cells

Cytotoxic effect(s) of N6-cycloalkylated adenine and adenosine derivatives, upon the viability of mouse hepatoma cells, were studied in vitro. N6-Cyclopropyl- and N6-cyclobutyladenine and adenosine derivatives (33 micrograms/ml; 24-48 h) exerted significant cytotoxic effects upon the cells. N6-Cyclopentyl- and N6-cyclohexyladenines exerted similar effects under different experimental conditions (133-166 micrograms/ml; 48-72 h), while no significant cytotoxic effect(s) were observed with the corresponding adenosine derivatives under these conditions. Observed physical changes in the treated cells included cell elongation, short stubby filaments, wide intracellular spaces and ruptured cell membranes. N6-Cycloalkylated nucleosides were usually more cytotoxic than the cycloalkylated bases.     

Quantum chemical study of the structure and properties of citrinin

Detailed structures and electronic properties of three tautomeric forms of the toxin citrinin were investigated using several quantum calculation methods. Energetic preference of the predominant p- and o-quinone methide tautomeric forms is dependent on the method of calculation. A previously unstudied carboxylic acid enol tautomer was calculated to be surprisingly stable in vacuo, being within 2.5 kcal mol^? 1 at the B3LYP/6-311++G(2d,2p) level of theory. Despite differences in bond nature and connectivity of tautomers, the natural bond orbital analysis revealed that tautomeric forms share similar natural charges and natural electron configurations. Calculated bond lengths corresponded with experimentally observed values and assignments for the calculated infrared vibrational frequencies are reported.     

Quantum chemical study of silanediols as metal binding groups for metalloprotease inhibitors

DFT (B3LYP and M06L) as well as ab initio (MP2) methods with Dunning cc-pVnZ (n?=?2,3) basis sets are employed for the study of the binding ability of the new class of protease inhibitors, i.e., silanediols, in comparison to the well-known and well-studied class of inhibitors with hydroxamic functionality (HAM). Active sites of metalloproteases are modeled by [R₃M-OH₂]²⁺ complexes, where R stands for ammonia or imidazole molecules and M is a divalent cation, namely zinc, iron or nickel (in their different spin states). The inhibiting activity is estimated by calculating Gibbs free energies of the water displacement by metal binding groups (MBGs) according to: [R₃M-OH₂]²⁺ + MBG → [R₃M-MBG]²⁺ + H₂O. The binding energy of silanediol is only a few kcal mol^?1 inferior to that of HAM for zinc and iron complexes and is even slightly higher for the triplet state of the (NH₃)₃Ni²⁺ complex. For both MBGs studied in the ammonia model the binding ability is nearly the same, i.e., Fe²⁺(t) > Ni²⁺(t) > Fe²⁺(q) > Ni²⁺(s) > Zn²⁺. However, for the imidazole model the order is slightly different, i.e., Ni²⁺(t) > Fe²⁺(t) > Fe²⁺(q) > Ni²⁺(s) ≥ Zn²⁺. Equilibrium structures of the R₃Zn ²⁺ complexes with both HAM and silanediol are characterized by the monodentate binding, but the bidentate character of binding increases on going to iron and nickel complexes. Two types of intermediates of the water displacement reactions for [(NH₃)₃M-OH₂]²⁺ complexes were found which differ by the direction of the attack of the MBG. Hexacoordinated complexes exhibit bidentate bonding of MBGs and are lower in energy for M=Ni and Fe. For Zn penta- and hexacoordinated complexes have nearly the same energy. Intermediate complexes with imidazole ligands have only octahedral structures with bidentate bonding of both HAM and dimethylsilanediol molecules.     

Quantum chemical study of agonist-receptor vibrational interactions for activation of the glutamate receptor

To understand the mechanism of activation of a receptor by its agonist, the excitation and relaxation processes of the vibrational states of the receptor should be examined. As a first approach to this problem, we calculated the normal vibrational modes of agonists (glutamate and kainate) and an antagonist (6-cyano-7-nitroquinoxaline-2,3-dione: CNQX) of the glutamate receptor, and then investigated the vibrational interactions between kainate and the binding site of glutamate receptor subunit GluR2 by use of a semiempirical molecular orbital method (MOPAC2000-PM3). We found that two local vibrational modes of kainate, which were also observed in glutamate but not in CNQX, interacted through hydrogen bonds with the vibrational modes of GluR2: (i) the bending vibration of the amine group of kainate, interacting with the stretching vibration of the carboxyl group of Glu705 of GluR2, and (ii) the symmetric stretching vibration of the carboxyl group of kainate, interacting with the bending vibration of the guanidinium group of Arg485. We also found collective modes with low frequency at the binding site of GluR2 in the kainate-bound state. The vibrational energy supplied by an agonist may flow from the high-frequency local modes to the low-frequency collective modes in a receptor, resulting in receptor activation.     

New ribose-modified fluorescent analogs of adenine and guanine nucleotides available as subtrates for various enzymes

The synthesis of fluorescent derivatives of nucleosides and nucleotides, by reaction with isatoic anhydride in aqueous solution at mild pH and temperature, yielding their 3′-O-anthraniloyl derivatives, is here described. The N-methylanthraniloyl derivatives were also synthesized by reaction with N-methylisatoic anhydride. Upon excitation at 330–350 nm these derivatives exhibited maximum fluorescence emission at 430–445 nm in aqueous solution with quantum yields of 0.12–0.24. Their fluorescence was sensitive to the polarity of the solvent; in N,N-dimethylformamide the quantum yields were 0.83–0.93. The major differences between the two fluorophores were the longer wavelength of the emission maximum of the N-methylanthraniloyl group and its greater quantum yield in water. All anthraniloyl derivatives, as well as the N-methylanthraniloyl ones, had virtually identical fluorescent properties, regardless of their base structures. The ATP derivatives showed considerable substrate activity as a replacement of ATP with adenylate kinase, guanylate kinase, glutamine synthetase, myosin ATPase and sodium-potassium transport ATPase. The ADP derivatives were good substrates for creatine kinase and glutamine syntletase (γ-glutamyl transfer activity). The GMP and adenosine derivatives were substrates for guanylate kinase and adenosine deaminase, respectively. All derivatives had only slightly altered K_m values for these enzymes. While more fluorescent in water, the N-methylanthraniloyl derivatives were found to show relatively low substrate activities against some of these enzymes. The results indicate that these ribose-modified nucleosides and nucleotides can be versatile fluorescent substrate analogs for various enzymes.     

New ribose-modified fluorescent analogs of adenine and guanine nucleotides available as substrates for various enzymes

The synthesis of fluorescent derivatives of nucleosides and nucleotides, by reaction with isatoic anhydride in aqueous solution at mild pH and temperature, yielding their 3'-O-anthraniloyl derivatives, is here described. The N-methylanthraniloyl derivatives were also synthesized by reaction with N-methylisatoic anhydride. Upon excitation at 330-350 nm these derivatives exhibited maximum fluorescence emission at 430-445 nm in aqueous solution with quantum yields of 0.12-0.24. Their fluorescence was sensitive to the polarity of the solvent; in N,N-dimethylformamide the quantum yields were 0.83-0.93. The major differences between the two fluorophores were the longer wavelength of the emission maximum of the N-methylanthraniloyl group and its greater quantum yield in water. All anthraniloyl derivatives, as well as the N-methylanthraniloyl ones, had virtually identical fluorescent properties, regardless of their base structures. The ATP derivatives showed considerable substrate activity as a replacement of ATP with adenylate kinase, guanylate kinase, glutamine synthetase, myosin ATPase and sodium-potassium transport ATPase. The ADP derivatives were good substrates for creatine kinase and glutamine synthetase (gamma-glutamyl transfer activity). The GMP and adenosine derivatives were substrates for guanylate kinase and adenosine deaminase, respectively. All derivatives had only slightly altered Km values for these enzymes. While more fluorescent in water, the N-methylanthraniloyl derivatives were found to show relatively low substrate activities against some of these enzymes. The results indicate that these ribose-modified nucleosides and nucleotides can be versatile fluorescent substrate analogs for various enzymes.     

Synthesis and kinetic study of transition state analogs for ribonuclease T1.

Based on the proposal that ribonucleases cleave the RNA phosphodiester bond with a mechanism involving pentacovalent phosphorous as transition state, complexes of guanosine and inosine with vanadate-(IV, V), molybdate-(VI), tungstate-(VI), chromate-(VI) and hexacyanochromate-(III) were synthesized and probed as inhibitors of recombinant ribonuclease T1, obtained from an E. coli. overproducing strain. The apparent dissociation constants of these inhibitors and RNase T1, as determined by Michaelis-Menten kinetics, vary between 0.5-0.9 microM and indicate very strong binding, 100- to 1000-fold stronger than the binding of guanosine (Kd = 545 microM) and inosine (Kd = 780 microM), and 50-100-fold stronger than the binding of the product 3' GMP (Kd = 55 microM). Therefore the synthesized inhibitors may be considered as genuine transition state analogs for the enzyme.     

青檀SRAP-PCR体系优化设计方案

以青檀(Pteroceltis tatarinowii Maxim.)叶片为材料,采用正交设计和均匀设计两种方法对SRAP-PCR反应体系进行优化,并对这两种设计方案优化出的最佳反应体系进行比较,结果表明:两种设计均可用于青檀SRAP-PCR体系的优化,但与正交设计相比,均匀设计在多因素多水平条件下,得到的条带更清晰、稳定性更好。通过实验比较筛选出的青檀SRAP-PCR最佳反应体系为:2.5μL 10×PCR buffer,20 ng模板DNA,Mg2+2.5 mmol/L,dNTP150μmol/L,引物0.2μmol/L,Taq DNA聚合酶1.0 U,总体积25μL。     

Quantum chemical study of relative reactivities of a series of amines and nitriles: Relevance to prebiotic chemistry

Using the Iterative Extended Hucken Theory (IEHT) calculations of the elctron distribution and orbital energies of a series of thirteen amines, nitriles and amino-nitriles relevant to prebiotic and cosmo-chemistry have been carried out. Ground state properties such as the energy and nature of the highest occupied (HOMO) and lowest empty (LEMO) molecular orbitals, net atomic charges and number of non-bonding electrons have been identified as criteria for correlating the relative nucleophilicity of amine and nitrile nitrogens and the electrophilicity of nitrile and other unsaturated carbon atoms. The results of such correlations can be partially verified by known chemical behavior of these compounds and are used to predict and understand their role in prebiotic organic synthesis.     

A sequence-based filtering method for ncRNA identification and its application to searching for riboswitch elements

MOTIVATION: Recent studies have uncovered an "RNA world", in which non coding RNA (ncRNA) sequences play a central role in the regulation of gene expression. Computational studies on ncRNA have been directed toward developing detection methods for ncRNAs. State-of-the-art methods for the problem, like covariance models, suffer from high computational cost, underscoring the need for efficient filtering approaches that can identify promising sequence segments and speedup the detection process. RESULTS: In this paper we make several contributions toward this goal. First, we formalize the concept of a filter and provide figures of merit that allow comparison between filters. Second, we design efficient sequence based filters that dominate the current state-of-the-art HMM filters. Third, we provide a new formulation of the covariance model that allows speeding up RNA alignment. We demonstrate the power of our approach on both synthetic data and real bacterial genomes. We then apply our algorithm to the detection of novel riboswitch elements from the whole bacterial and archaeal genomes. Our results point to a number of novel riboswitch candidates, and include genomes that were not previously known to contain riboswitches. AVAILABILITY: The program is available upon request from the authors.     

Synthesis of 2',5'-oligoadenylate analogs containing an adenine acyclonucleoside and their ability to activate human RNase L

This paper described synthesis of 2',5'-oligoadenylate (2-5A) analogs containing the purine acyclonucleoside, 9-[(2'S,3'R)-2',3',4'-trihydroxybutyl]adenine (2). The ability of the analogs to activate recombinant human RNase L was evaluated using 5'-32P-r(C11U2C7)-3' as a substrate. The EC50 value (the concentration of the 2-5A required to cleave half of the RNA) of the parent 2-5A tetramer 13 was 1.0 nM, whereas those of the analog 14 incorporating 2 at the second position from the 5'-end and the analog 15 incorporating 2 at the third position from the 5'-end were 9.0 and 1.7 nM, respectively. The analogs 14 and 15 were only 9- and 1.7-fold less potent than the parent 2-5A 13 itself, in RNase L activation ability. Furthermore, the oligodeoxynucleotide containing 2 was more resistant to nucleolytic hydrolysis by snake venom phosphodiesterase (a 3'-exonuclease) than the unmodified oligodeoxynucleotide. Thus, incorporation of an acyclonucleoside into 2-5A may be useful for developing an antiviral agent based on the 2-5A system.     

Quantum chemical study of the thermodynamics,kinetics of formation and bonding of H2CN relevance to prebiotic chemistry

Using the Iterative Extended Huckel Theory (IEHT), energy-conformation studies have been carried out for H₂CN (I),trans-HCNH (IIA), andcis-HCNH (IIB), three possible isomers formed by addition of a hydrogen atom to hydrogen cyanide. Calculations show that the order of decreasing thermodynamic stability is I≫IIA>IIB. Additionally, from calculated energies along simulated reaction pathways, the formation of I from HCN+H appears to be kinetically favored over IIA. Calculated properties of the minimum energy conformers of I and IIA are described and the potential role of H₂CN (I) as a reactive intermediate in prebiotic organic synthesis and its possible relevance to interstellar organic chemistry are discussed.