Effective Detection of Phenylalanine Using Pyridine Based Sensor.

Pyridine based organic molecule as probe has been synthesized for the detection of phenylalanine (PA) biomarker. The synthesized probe is characterized by 1H and 13C NMR and mass spectroscopic studies. The photophysical properties for the probe has recorded by colorimetric and fluorimetric techniques. The quenching has been observed between the probe and PA through ICT (Intermolecular Charge Transfer Mechanism). Under optimized conditions, the probe detects PA selectively in the presence of other biologically important biomolecules. The practical application for PA has been successfully applied in human blood serum and urine.

Development of Optical Biosensor for the Detection of Glutamine in Human Biofluids Using Merocyanine Dye.

Merocyanine dye based fluorescent organic compound has been synthesized for the detection of glutamine. The probe showed remarkable fluorescent intensity with glutamine through ICT (Intermolecular Charge Transfer Mechanism). Hence, it is tested for the detection of glutamine using colorimetric and fluorimetric techniques in physiological and neutral pH (7.2). Under optimized experimental conditions, the probe detects glutamine selectively among other interfering biomolecules. The probe has showed a LOD (lower limit of detection) of 9.6 × 10-8 mol/L at the linear range 0-180 µM towards glutamine. The practical application of the probe is successfully tested in human biofluids.

Atomistic simulation on flavonoids derivatives as potential inhibitors of bacterial gyrase of Staphylococcus aureus.

The bacterial DNA gyrase is an attractive target to identify the novel antibacterial agents. The flavonoid derivatives possess various biological activities such as antimicrobial, anti-inflammatory and anticancer activities. The aim of present study is to identify the potential molecule from flavonoid derivatives against Staphylococcus aureus using atomistic simulation namely Molecular Docking, Quantum Chemical and Molecular Dynamics. The molecules Cpd58, Cpd65 and Cpd70 are identified as potential molecules through molecular docking approaches by exploring through the N - H…O hydrogen bonding interactions with Asn31 and Glu35 of Gyrase B. To confirm the intramolecular charge transfer in the flavonoid derivatives, Frontier Molecular Orbital (FMO) calculation was performed at M06/6-31g(d) level in gas phase. The lowest HOMO-LUMO gap was calculated for Cpd58, Cpd65 and Cpd70 among the selected compounds used in this study. Molecular dynamics simulation were carried out for Cpd58 and Cpd70 for a time period of 50 ns and found to be stable throughout the analysis. Therefore, the identified compounds are found to be a potent inhibitor for GyrB of S. aureus that can be validated by experimental studies. Communicated by Ramaswamy H. Sarma.

Rationally designed imidazole derivative as colorimetric and fluorometric sensor for selective, qualitative and quantitative cyanide ion detection in real time samples.

A new imidazole derivative of 1,2-diaminoanthraquinone and fluorene-2-carboxaldehyde was designed as a sensor B2 to selectively detect the cyanide (CN-) ion through colorimetric and/or fluorometric methods. The photochemical characterizations of sensor B2 were tested using absorption and emission spectral studies in CH3CN-H2O (8:2) semi-aqueous medium. An excited state proton transfer process (ESIPT) was proved by theoretical and spectral studies. The colorimetric and fluorescence detection limit of CN- ion was found to be 5.3 × 10-6 M and 4.11 × 10-8 M, respectively. 1H NMR titration, electrochemical and DFT studies were supported the removal of -NH proton from B2. In order to utilize this sensor in real-time applications, we developed a test cassette which is coated with sensor B2 detected the presence of CN- ion in the food sample with endogenous cyanide ion.

Eco-Friendly Sustainable Poly(benzoxazine-co-urethane) with Room-Temperature-Assisted Self-Healing Based on Supramolecular Interactions.

This work is an attempt to develop bio-based eco-friendly poly(benzoxazine-co-urethane) [poly(U-co-CDL-aee)] materials using cardanol-based benzoxazines (CDL) and hexamethylene diisocyanate (HMDI) to check their self-healing ability and thermal properties. CDL monomers were synthesized using cardanol, amino ethoxyethanol (aee) or 3-aminopropanol (3-ap), and paraformaldehyde through the Mannich reaction. Later, CDL-aee or CDL-3-ap monomers were copolymerized with a urethane precursor (HMDI), followed by ring-opening polymerization through thermal curing. The thermal properties of poly(U-co-CDL) were evaluated by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). The self-healing behavior of the bio-based poly(U-co-CDL) was checked by applying a mild external pressure. The results revealed that the developed poly(U-co-CDL) showed repeatable self-healing ability due to supramolecular hydrogen-bonding interactions. Further, the self-healing ability of poly(U-co-CDL) was studied using density functional theory (DFT). From the above results, the developed material with superior self-healing ability can be used in the form of self-healing coatings and composites for various applications with extended shelf-life and reliability.

Highly Selective and Sensitive Colorimetric and Fluorimetric Sensor for Cu2.

A newly designed fluorescent and colorimetric probe was synthesized and selective detection of cu2+ was successful in aqueous medium. The design strategy exhibited strongly fluorescent when binding with cu2+ based on the change in structure between spirocyclic to a non-cyclic form of rhodamine based dye. The UV visible spectra of probe (6GS2) exhibited three absorption peaks at 229, 309 and 530 nm respectively. The emission spectra of fluorescent probe exhibited wavelength at 550 nm. The peak intensity increases during the addition of copper ion to probe through n-π transition. The probe characterized by different techniques like NMR, absorption, emission, mass and test strips methods. Graphical Abstract .

On the misincorporation of nucleotides opposite mutagenic cyclic 1,N2-propanoguanine: A computational investigation.

The misincorporation properties of exocyclic DNA adduct, cyclic 1,N2-propanoguanine with nucleobases have been investigated using DFT and DFT-D methods. Number of possible and stable mispairing conformations of cyclic 1,N2-propanoguanine with A,T,G and C have been considered for our investigation. The single point energy calculations have been carried out at the M06/6-311++G**, ωB97XD/6-311++G** and MP2/6-311++G** levels on corresponding optimized geometries. The reaction enthalpy values were employed at the M06/6-31 + G* and ωB97XD/6-31 + G* levels. The energies have been compared among the cyclic 1,N2-propanoguanine adduct with nucleobases to find the most stable conformer. The CPCM model was utilized on account of solvent phase and overall polarizability. The computed binding energies follow the order as CPr-Gua-G(2)(-23.2 kcal/mol) > CPr-Gua-C(1) (-16.1 kcal/mol) > CPr-Gua-A(2)(-10.6 kcal/mol) > CPr-Gua-T(2)(-9.6 kcal/mol) in the gas phase at M06 level, which indicates the guanine and cytosine are favorable for mispairing with the cyclic 1,N2-propanoguanine adduct. The obtained results using computational tools are in good agreement with the experimental observation.

Intramolecular hydroarylation of aryl propargyl ethers catalyzed by indium: the mechanism of the reaction and identifying the catalytic species.

The mechanism and regioselectivity of the intramolecular hydroarylation of phenyl propargyl ether catalyzed by indium in gas and solvent phases were investigated by means of the density functional theory method. The computed results revealed that the reaction proceeds through initial π-coordination of the propargyl moiety to the catalyst, which triggers the nucleophilic attack of the phenyl ring via an exo- or endo-dig pathway in a Friedel-Crafts type mechanism. Calculation results obtained employing InI2(+) as the possible catalyst show similar activation energies for the 5-exo-dig and 6-endo-dig pathways. In contrast, the neural catalyst InI3 shows a kinetic preference for 6-endo-dig versus 5-exo-dig cyclizations leading to the experimentally observed product, 2H-chromene. The calculation results suggest that InI3 could be the real catalytic species for this reaction as it shows regioselectivity in agreement with the experimental observation. Furthermore, the 6-endo-dig cyclization through deprotonation/protonation steps is kinetically more favored than the stepwise two consecutive [1,2]-H shift steps. The rate determining step of the whole catalytic cycle is the deprotonation step with an energy barrier of 18.9 kcal mol(-1) in toluene solvent. The effects of substituents on both the phenyl ring and the propargyl moiety on the selectivity and elementary steps of the hydroarylation process were investigated. A methoxy group, particularly at the meta-position, on the phenyl ring largely decreases the energy barrier of the first step for the 6-endo path, though it shows little effect on the activation energies of the second and third steps. Our calculation results are in good agreement with the experimental results.

Quantum mechanistic insights on aryl propargyl ether Claisen rearrangement.

The mechanism of aryl propargyl ether Claisen rearrangement in gas and solvent phase was investigated using DFT methods. Solvent phase calculations are carried out using N,N-diethylaniline as a solvent in the PCM model. The most favorable pathways involve a [3,3]-sigmatropic reaction followed by proton transfer in the first two steps and then deprotonation or [1,5]-sigmatropic reaction. Finally, cyclization yields benzopyran or benzofuran derivatives. The [3,3]-sigmatropic reaction is the rate-determining step for benzopyran and benzofuran with ΔG(‡) value of 38.4 and 37.9 kcal mol(-1) at M06/6-31+G**//B3LYP/6-31+G* level in gas and solvent phase, respectively. The computed results are in good agreement with the experimental results. Moreover, it is found that the derivatives of aryl propargyl ether proceeded Claisen rearrangement and the rate-determining step may be shifted from the [3,3]-sigmatropic reaction to the tautomerization step. The NBO analysis revealed that substitution of the methyl groups on the aliphatic segment has decreased the stabilization energy E(2) and favors the aryl propargyl ether Claisen rearrangement.

Spectroscopic probe on N-H⋯N, N-H⋯O and controversial C-H⋯O contact in A-T base pair: a DFT study.

DNA base pair A-T has been investigated by IR and NMR spectroscopy using DFT methods. The results have been analyzed in terms of infrared vibrational frequencies and (1)H NMR chemical shifts. Different types of interactions N-H⋯N, N-H⋯O and C-H⋯O types have been investigated in DNA base pairs. Although, previous reports argued about the third C-H⋯O type interaction in A-T base pair, such typical interaction has been analyzed thoroughly by IR and NMR spectroscopy using DFT methods. Our results show that the CH⋯O interaction in the A-T base pair is a weak interaction compared to normal hydrogen bond interactions.

Correlation between substituent constants and hyperpolarizabilities for di-substituted trans-azobenzenes.

Nonlinear optical properties of a series of disubstituted trans-azobenzenes were studied. The structures were fully optimized by B3LYP/6-31+G* and both static polarizabilities and hyperpolarizabilities were then calculated by the derivative method. In order to show the relationships between dipole moments, (hyper)polarizabilities and the structures, three kinds of substituent constants were applied to correlate with both ground state dipole moment and hyperpolarizabilities. Both physical properties have a satisfactory correlation with substituent constants Σσ(+/-) and bond length alternation. Overall, the electronic excitation contribution to the hyperpolarizabilities is rationalized in terms of the two-level model.

Stability computations for isomers of La@C(n) (n = 72, 74, 76).

Density-functional theory calculations are presented for low-energy La@C72, La@C74 and La@C76 isomers with IPR (isolated pentagon rule) and non-IPR cages. The relative isomeric production yields at high temperatures are evaluated using the calculated terms, and the relationships to observations are discussed.

Quantum mechanical calculations for the misincorporation of nucleotides opposite mutagenic 3,N4-ethenocytosine.

The ubiquitous nature and persistence of exocyclic DNA adducts suggest their involvement as initiators of carcinogenesis. We have investigated the misincorporation properties of the exocyclic DNA adduct, 3,N(4)-ethenocytosine, using DFT and DFT-D methods. Computational investigations have been carried out by using the B3LYP, M062X, and wB97XD methods with the 6-31+G* basis set to determine the hydrogen bonding strengths, binding energy, and physical parameters. The single point energy calculations have been carried out at MP2/6-311++G** on corresponding optimized geometries. The energies were compared among the 3,N(4)-ethenocytosine adduct with DNA bases to find the most stable conformer. The solvent phase calculations have also been carried out using the CPCM model. The computed reaction enthalpy values provide computational insights to the earlier experimental observation in in vitro, E.coli, and mammalian cells of a high level of substitution mutation in which C → A transversion results from εC-T pairing [εC-T3 and εC-T4] in the adduct containing DNA sequence.

Computational investigation on microsolvation of the osmolyte glycine betaine [GB (H(2)O)(1-7)].

The preferential interactions of glycine betaine (GB) with solvent components and the effect of solvent on its stability have been examined. In particular, the microsolvation of organic osmolyte and widely important osmoprotectant in nature as glycine betaine has been reported by using M06 method. A number of configurations (b(X) (a-z)) of the clusters for one to seven water molecules (× = 1-7) have been considered for the microsolvation. Structures of stable conformers are obtained and denoted as b1a, b2a, b3a, b4a, b5a, b6a and b7a. It is observed from the interaction energy difference (∆E) that only seven water molecules can be accommodated in the first solvation shell to stabilize GB. It is also observed that the calculated relative energy using M06 is in close agreement with calculations at the MP2 level of theory.

Cooperativity effects in linear formaldehyde oligomers using density functional theory calculations.

This work reports hydrogen bonding interaction in linear formaldehyde oligomers using density functional theory method. Many-body analysis technique has been used to study the various interactions in these oligomers and to obtain % contributions from individual many-body energy terms to the binding energies of these oligomers. Co-operativity effects are studied using different indicators viz. hydrogen bond strength, inter- and intramolecular distances, dissociation energy, dipole co-operativity, energy per hydrogen bond, excess energy and non-additive energy. All these indicators show strong positive hydrogen bond co-operativity in linear formaldehyde oligomers. The dipole moment changes from 2.51 D in monomer to 20.92 D in formaldehyde heptamer.

Verification of DFT-predicted hydrogen storage capacity of VC3H3 complex using molecular dynamics simulations.

Density functional theory (DFT) and Fourth-order Möller-Plesset (MP4) perturbation theory calculations are performed to examine the possibility of hydrogen storage in V-capped VC(3)H(3) complex. Stability of bare and H(2) molecules adsorbed V-capped VC(3)H(3) complex is verified using DFT and MP4 method. Thermo-chemistry calculations are carried out to estimate the Gibbs free corrected averaged H(2) adsorption energy which reveals whether H(2) adsorption on V-capped VC(3)H(3) complex is energetically favorable, at different temperatures. We use different exchange and correlation functionals employed in DFT to see their effect on H(2) adsorption energy. Molecular dynamic (MD) simulations are performed to confirm whether this complex adsorbs H(2) molecules at a finite temperature. We elucidate the correlation between H(2) adsorption energy obtained from density functional calculations and retaining number of H(2) molecules on VC(3)H(3) complex during MDs simulations at various temperatures.

Model calculations for the misincorporation of nucleotides opposite five-membered exocyclic DNA adduct: N(2),3-ethenoguanine.

Five-membered exocyclic DNA adducts are biologically very significant because of their potential to block DNA replication and transcription. N(2),3-Ethenoguanine (N(2,3)-εG) has been identified in the liver DNA of vinyl chloride-exposed rats as a five-membered DNA adduct. Singer et al. ( Carcinogenesis 1987 , 8 , 745 - 747 ) reported that the misincorporation of thymine (T), with two hydrogen bonds to N(2,3)-εG, represents the mutagenic event. Although the base-pairing specificity and mode of misincorporation have been studied experimentally for the N(2),3-ethenoguanine adduct, molecular-level information is not yet clear. In this study, we have considered all four different DNA nucleotides paired with the N(2),3-ethenoguanine adduct for model calculations toward the determination of base-pairing specificity. To provide insight into the mutagenic process of DNA damage based on geometric characteristics and electronic properties, the B3LYP and M06 methods were employed for these model calculations. Single-point energy calculations at the MP2/6-311++G** level on the corresponding optimized geometries were also carried out to better estimate the hydrogen-bonding strengths. The polarizable conductor calculation model (CPCM), which accounts for the overall polarizability of the solvent, was also employed. The computed reaction enthalpy values lie in the order εG-G(2) (10.3 kcal/mol) > εG-G(4) (9.6 kcal/mol) > εG-T(4) (9.2 kcal/mol) > εG-G(1) (9.1 kcal/mol) > εG-A(5) (8.2 kcal/mol) > εG-C(2) (7.9 kcal/mol) at the M06 level, which indicates that guanine and thymine are most favorable for mispairing with the N(2),3-ethenoguanine adduct.

Many-body energies during proton transfer in an aqueous system.

The energetics of the mechanism of proton transfer from a hydronium ion to one of the water molecules in its first solvation shell are studied using density functional theory and the Møller-Plesset perturbation (MP2) method. The potential energy surface of the proton transfer mechanism is obtained at the B3LYP and MP2 levels with the 6-311++G** basis set. Many-body analysis is applied to the proton transfer mechanism to obtain the change in relaxation energy, two-body, three-body and four-body energies when proton transfer occurs from the hydronium ion to one of the water molecules in its first solvation shell. It is observed that the binding energy (BE) of the complex decreases during the proton transfer process at both levels of theory. During the proton transfer process, the % contribution of the total two-body energy to the binding energy of the complex increases from 62.9 to 68.09% (39.9 to 45.95%), and that of the total three-body increases from 25.9 to 27.09% (24.16 to 26.17%) at the B3LYP/6-311++G** (MP2/ 6-311++G**) level. There is almost no change in the water-water-water three-body interaction energy during the proton transfer process at both levels of theory. The contribution of the relaxation energy and the total four-body energy to the binding energy of the complex is greater at the MP2 level than at the B3LYP level. Significant differences are found between the relaxation energies, the hydronium-water interaction energies and the four-body interaction energies at the B3LYP and MP2 levels.

Interaction of serotonin and fluoxetine: toward understanding the importance of the chirality of fluoxetine (S form and R form).

The present investigation reports the importance of the S and R forms of fluoxetine, as an antidepressant with regards to the chirality taking different types of interactions associated with the neurotransmitter, serotonin. The goal of the present study is to provide predictions and to help experimental and theoretical studies toward understanding the chirality of fluoxetine in drug-ligand interaction, associated with serotonin-reuptake inhibitor drug design studies. Several different conformations for serotonin and fluoxetine complexes have been considered for quantum mechanical calculations. Both the S and R forms of fluoxetine associated with serotonin and fluoxetine complexes are found to be similar in total energy and binding energy values. The present study also supports the conformational effect of the 3-phenyl group of fluoxetine as stereo independent and is consistent with in vitro and in vivo data which indicates that the the eudismic ratio of fluoxetine enantiomers is near unity. The calculated highest stabilization energy values, binding energy values, both in the gas and aqueous phases at MP2/6-31+G*//B3LYP/6-31+G* identify the most possible stable conformer for the serotonin-fluoxetine complex.

Effect of microsolvation on zwitterionic glycine: an ab initio and density functional theory study.

The effect of microsolvation on zwitterionic glycine, considering both (-NH3(+)) as proton donor and (-COO(-)) as proton acceptor at correlated ab initio (MP2) level and density functional methods (B3LYP, PW91, MPW1PW91 and PBE) using 6-311++G** basis set has been reported. DFT methods have been employed so as to compare the performance/quality of different gradient-corrected correlation functionals (PW91, PBE), hybrid functionals (B3LYP, MPW1PW91) and to predict the near quantitative structural and vibrational properties, at reduced computational cost. B3LYP method outperforms among the different DFT methods for the computed hydrogen bond distances and found closer to the value obtained by correlated MP2 level, whereas MPW1PW91 and PBE methods shows very similar values but approximately 0.03 A less, compared to B3LYP method. MP2 calculation and single point CCSD(T)//MP2 calculation have been considered to decompose the interaction energy, including corrections for basis set superposition error (BSSE). Moreover, charge distribution analysis has also been carried out to understand the long raised questions, how and why the two body energies have significant contribution to the total binding energy.