Pabitra Narayan Samanta

Noncovalent interaction assisted fullerene for the transportation of some brain anticancer drugs: A theoretical study

The treatment of brain cancer like glioblastoma multiforme often uses chemotherapeutic drugs like temozolomide, procarbazine, carmustine, and lomustine. Fullerene loaded with these drugs help to cross the blood brain barriers. The adsorptions of the four drug molecules on the surface of the fullerene are studied mostly by using density functional theory (DFT) based method at the M06-2X/6-31G(d) level of calculations. In all four cases, the estimated interactions are noncovalent type and the average adsorption energy lies in between -5 and -11kcal/mol in the gas phase. In the aqueous and protein environment such interactions are weakened further. The binding affinity is further assessed by performing MP2 based calculations to provide interaction energies with a reasonable accuracy. Stabilities and reactivities of the drug adsorbed fullerene complexes are determined from chemical reactivity descriptors. The attached drug molecules increase the polarity of the pristine C60 thus facilitating the drug delivery within the biological systems. The semiconducting behavior of C60 is retained in the C60-drug composite systems. The computed DOS, IR, UV spectra, and molecular orbitals in the vicinity of Fermi level are analyzed to reveal the nature of the noncovalent interactions between C60 and drug molecules. The Wiberg bond order values are used to estimate the strength of the adsorption of the drug molecule on C60. In all four C60-drug interactions, the chemical characteristics of the drug molecule are least perturbed by the C60 moiety thereby suggesting it to be a good carrier for the delivery of these brain anticancer drug molecules to the target cells.

Prediction of binding modes and affinities of 4-substituted-2,3,5,6-tetrafluorobenzenesulfonamide inhibitors to the carbonic anhydrase receptor by docking and ONIOM calculations.

Inhibition activities of a series of 4-substituted-2,3,5,6-tetrafluorobenzenesulfonamides against the human carbonic anhydrase II (HCAII) enzyme have been explored by employing molecular docking and hybrid QM/MM methods. The docking protocol has been employed to assess the best pose of each ligand in the active site cavity of the enzyme, and probe the interactions with the amino acid residues. The docking calculations reveal that the inhibitor binds to the catalytic Zn(2+) site through the deprotonated sulfonamide nitrogen atom by making several hydrophobic and hydrogen bond interactions with the side chain residues depending on the substituted moiety. A cross-docking approach has been adopted prior to the hybrid QM/MM calculation to validate the docked poses. A correlation between the experimental dissociation constants and the docked free energies for the enzyme-inhibitor complexes has been established. Two-layered ONIOM calculations based on QM/MM approach have been performed to evaluate the binding efficacy of the inhibitors. The inhibitor potency has been predicted from the computed binding energies after taking into account of the electronic phenomena associated with enzyme-inhibitor interactions. Both the hybrid (B3LYP) and meta-hybrid (M06-2X) functionals are used for the description of the QM region. To improve the correlation between the experimental biological activity and the theoretical results, a three-layered ONIOM calculation has been carried out and verified for some of the selected inhibitors. The charge transfer stabilization energies are calculated via natural bond orbital analysis to recognize the donor-acceptor interaction in the binding pocket of the enzyme. The nature of binding between the inhibitors and HCAII active site is further analyzed from the electron density distribution maps.

5-Aminolevulinic acid functionalized boron-nitride and carbon nanotubes as drug delivery vehicles for skin anticancer drugs: a theoretical study

An improved delivery of 5-aminolevulinic acid (ALA), a drug used for skin anticancer therapy depends on the nature of the drug carrier. The electronic structure and properties of ALA functionalized zigzag and armchair boron-nitride nanotubes (BNNTs) are studied using density functional theory (DFT) calculations at the B3LYP/6-31G(d) level. A comparison has been made with the results of the corresponding carbon nanotube (CNT)–ALA complexes. The computed interaction energies and changes in Gibbs free energies suggest that the functionalization of BNNTs with ALA are more favorable than those of CNTs. IR vibrational analyses of some important chemical bonds in BNNT–ALA and CNT–ALA complexes have been made to explore any changes in the binding characteristics of the drug molecule after its attachment to the nanotubes. The calculated NBO charges, HOMO–LUMO gaps, and DOS spectra of the pristine and ALA functionalized nanotubes indicate that the end functionalization of the nanotubes by the ALA molecule does not alter the electronic properties of the pristine nanostructures or ALA significantly. The attachment of the drug molecule to the nanotube changes the polarity of the pristine nanotube as shown by the computed dipole moment values. The stabilities and reactivities of these nanotube–drug complexes have been tested from the magnitudes of the chemical reactivity descriptors such as chemical potential, hardness, and electrophilicity index. The effects of the protein core and aqueous environment on the BNNT–ALA interaction energies have been investigated by using the IEF-PCM model. The computed solvation energies show that the solubilities of ALA functionalized BNNTs are enhanced to a greater extent compared to the pristine ones. BNNTs can thus act as a drug delivery vehicle for the transportation of skin anticancer drugs within the biological system.

Adsorption of CO, SO2, HCN, NH3, and H2CO on zigzag GaP nanotubes: a QM/MM study

The interactions of the single-walled zigzag (5, 0), (6, 0), and (7, 0) GaP nanotubes (GaPNTs) with CO, SO2, HCN, NH3, and H2CO molecules are theoretically studied at the ONIOM(B3LYP/6-31G(d):UFF) level. A pyrene-like ring of the nanotube is chosen as an adsorption site in the high layer of the ONIOM calculations for the adsorption of a single molecule. Binding energy, Gibbs free energy change, density of states, and Mulliken charge transfer are computed to analyze the nature of the binding between GaPNT and the adsorbate molecule. The bindings of CO and H2CO towards GaPNTs are weaker than those of NH3, SO2, and HCN molecules. The strongest adsorption is found to be with NH3. The dispersion corrected functional (wB97XD) has been introduced to compare the results with those of the B3LYP functional.

Electronic structures, stabilities and spectroscopic properties of Pb m Si n (m + n ≤ 6) clusters

Electronic structures of neutral lead–silicon clusters of up to six atoms are determined by global optimization of the potential energy hyper surface using Metropolis Monte Carlo and genetic algorithm (GA) methods followed by a bond strength propensity model, and by local optimization using density functional theory at the B3LYP/aug-cc-pVTZ-pp level. For each cluster, geometries of those stable isomers whose relative energies are within 1.0 eV are reported. Average binding energy per atom, band gap, ionization potential (IP), electron affinity (EA), and vertical detachment energy of the most stable isomer of each type of cluster are computed to study their dependences on the size of the cluster. Polarizability, chemical potential, hardness and electrophilicity index of the most stable isomers are estimated to study their relative stabilities and chemical reactivities. Relative strengths of metal–metal interactions are determined from a study of all one-step fragmentation processes. IR intensities and Raman activities for all the vibrational modes of the most stable isomers are calculated.

Inhibition activities of catechol diether based non-nucleoside inhibitors against the HIV reverse transcriptase variants: Insights from molecular docking and ONIOM calculations

The therapeutic effectiveness of the catechol diether analogs against both the wild-type and drug-resistant reverse transcriptase (RT) mutants of HIV strains are investigated by performing molecular docking and hybrid ONIOM calculations. The docking protocol has been used to predict the binding modes of the non-nucleoside inhibitors inside the active site cavity of the viral enzymes. For each enzyme-inhibitor adduct, the predicted docked poses are assessed by employing different scoring function based programs. However, the docking protocol fails to explain satisfactorily the antiviral activities of the drug molecules. Two-layered ONIOM calculations have been carried out to compute the relative binding affinities of the catechol diether derivatives to the binding pockets of RT variants. The binding efficacies of the inhibitors are significantly suppressed by the Y181C and K103N mutations, as revealed by the computed interaction energies at the ONIOM [B3LYP/6-31G(d,p):PM6] level of theory. Deformation energies for each bound ligand conformer are also estimated. The nature of interactions between the drug molecules and the active site residues are analyzed from the reduced density gradient (RDG) isosurfaces. The simulated ECD spectra support the conformational adaption upon inhibitor binding in the binding pockets of HIV strains.

Structural and electronic properties of covalently functionalized 2-aminoethoxy-metallophthalocyanine–graphene hybrid materials: a computational study

The formation of a strong covalent bond between graphene and 2-aminoethoxy metallophthalocyanine (AEMPc) with the metal atom (M) being Zn, Fe, and Ni is established from density functional theory (DFT) based calculations at the B3LYP/6-31G(d)/LANL2DZ level of theory. The optimized structures of the hybrid complexes, represented by AEMPc–graphene, are reported. The projected density of states (PDOS) spectrum of each molecule has been calculated to explore the change in the HOMO–LUMO gap due to anchoring of AEMPc to graphene. The IR peak-positions and intensities obtained for the newly formed C–H and C–N bonds confirm the covalent link between the two moieties. The computed Raman spectra of the hybrid complexes show some changes in the relative intensities of D and G bands of graphene in accordance to those observed experimentally in a similar graphene based hybrid material. TDDFT calculations are carried out to study their absorption spectra in DMF solvent. For all three metal atoms in the composite molecules, there appears a charge transfer band in the range 600–630 nm. Three long-range corrected functionals such as M06-2X, CAM-B3LYP, and wB97XD are used to compare the results with those of the hybrid B3LYP functional.

MRDCI study of the low-lying electronic states of PbSi.

Electronic states of the PbSi molecule up to 4 eV have been studied by carrying out ab initio based MRDCI calculations which include relativistic effective core potentials (RECPs) of both the atoms. The use of semicore RECPs of Pb produces better dissociation limits than the full-core one. However, the (3)P(0)-(3)P(1) splitting due to Pb is underestimated by about 4000 cm(-1). At least 25 bound electronic states of the Λ-S symmetry are predicted for PbSi. The computed zero-field-splitting in the ground state is about 544 cm(-1). A strong spin-orbit mixing changes the nature of the potential energy curves of many Ω states. The overall splitting among the spin components of A(3)Π is computed to be 4067 cm(-1). However, the largest spin-orbit splitting is reported for the (3)Δ state. A number of spin-allowed and spin-forbidden transitions are predicted. The partial radiative lifetime for the A(3)Π-X(3)Σ(-) transition is of the order of milliseconds. The computed bond energy in the ground state is 1.68 eV, considering the spin-orbit coupling. The vertical ionization energy for the ionization to the X(4)Σ(-) ground state of PbSi(+) is about 6.93 eV computed at the same level of calculations.