Theoretical studies of phosphorene as a drug delivery nanocarrier for fluorouracil.

The interactions between phosphorene nanosheets (PNSs) and 5-fluorouracil (FLU) were explored using the density functional theory (DFT) method and molecular dynamics (MD) simulations. DFT calculations were performed utilizing M06-2X functional and the 6-31G(d,p) basis set in both gas and solvent phases. Results showed that the FLU molecule is adsorbed horizontally on the PNS surface with an adsorption energy (Eads) of -18.64 kcal mol-1. The energy gap (Eg) between the highest occupied and lowest unoccupied molecular orbitals (HOMO and LUMO, respectively) of PNS remains constant after the adsorption process. The adsorption behavior of PNS is not affected by carbon and nitrogen doping. The dynamical behavior of PNS-FLU was studied at T = 298, 310, and 326 K reminiscent of room temperature, body temperature, and temperature of the tumor after exposure to 808 nm laser radiation, respectively. The D value decreases significantly after the equilibration of all systems so that the equilibrated value of D is about 1.1 × 10-6, 4.0 × 10-8, and 5.0 × 10-9 cm2 s-1 at T = 298, 310, and 326 K, respectively. About 60 FLU molecules can be adsorbed on both sides of each PNS, indicating its high loading capacity. PMF calculations demonstrated that the release of FLU from PNS is not spontaneous, which is favorable from a sustained drug delivery point of view.

Exploration of phosphorene as doxorubicin nanocarrier: An atomistic view from DFT calculations and MD simulations.

Potential capability of phosphorene nanosheet (PNS) as doxorubicin (DOX) nanocarrier was investigated using density functional theory (DFT) method and molecular dynamics (MD) simulations. Both DFT calculations and MD simulations revealed that the DOX molecule is adsorbed horizontally onto the PNS surface with the nearest interaction distance of 2.5 Å. The binding energy of DOX is predicted to be about - 49.5 kcal.mol-1, based on the DFT calculations. After DOX adsorption, the Eg value of PNS remains almost constant in both gas and solvent phases. The dynamical behavior of PNS-DOX was studied at T = 298, 310, and 326 K that reminiscent of room temperature, body temperature, and temperature of tumor after exposure to 808 nm laser radiation, respectively. The diffusion coefficient values of DOX molecule are proportional to temperature. We found that PNS can hold a high amount of DOX on both sides of its surface (66% in weight). MD simulations showed that the dynamical behavior of simulated systems are not affected by pH variances.

PAMAM and polyester dendrimers as favipiravir nanocarriers: a comparative study using DFT method.

The electronic sensitivity and reactivity of polyamidoamine (PAMAM) and polyester dendrimers toward favipiravir (T705) were inspected using density functional theory method. The T705 drug is adsorbed on the surface of PAMAM and polyester dendrimers with the binding energy of -27.26 and -26.80 kcal mol-1, respectively, in the solvent phase. The energy gap of PAMAM and polyester dendrimers reduced by about 32% and 27%, indicating that the electrical conductance of carriers become 8.16 × 1023 and 4.41 × 1022 times higher, upon T705 adsorption. The work function (Φ) value of PAMAM and polyester is changed about 1.53 and 0.71 eV, respectively. Thus, PAMAM dendrimer is about 2.5 times stronger Φ-type sensor than polyester dendrimer. The recovery time for T705 desorption from the PAMAM and polyester surface is predicted to be 9.2 × 103 and 4.2 × 103 s, respectively, at physiological environment.

CNT-based nanocarrier loaded with pyrimethamine for adipose mesenchymal stem cells differentiation and cancer treatment: The computational and experimental methods.

Pyrimethamine is an effective drug in the cancer cell treatment and is a dihydrofolate reductase inhibitor. In this work, the amount of drug loading up on CNT and its cytotoxicity effect upon MCF-7 cell lines was surveyed. The novel applications of some drugs and nanocarriers can induce the differentiation of adipose mesenchymal cells into nerve cells. Hence carbon nanotube-pyrimethamine was used to differentiate mesenchymal stem cells into the neural category, for the first time. The results of NSE and NFM gene expression level were evaluated using the real-time PCR. A detailed study on the interaction between pyrimethamine anticancer drug and (6, 0) zigzag single-walled carbon nanotube was performed by DFT/B3LYP and DFT/M06-2X with 6-31G* basis set calculations in gas phase and in solvent using the PCM. Different configurations of the adsorbed pyrimethamine onto the CNT surface were studied. Based on the results, the process of pyrimethamine adsorption on diff ;erent sites on the outer wall of the nanotube was exothermic and configurations were stable. The adsorption energy values indicated that the pyrimethamine molecule could be physically adsorbed on the external surface of the SWCNT. The QTAIM was used for characterizing the nature of the interactions between the pyrimethamine and the selected nanocarrier.

Tracing chirality, diameter dependence, and temperature-controlling of single-walled carbon nanotube non-covalent functionalization by biologically compatible peptide: insights from molecular dynamics simulations.

Biological applications of single-walled carbon nanotubes (SWCNTs), including drug delivery, require their functionalization with various functional groups such as peptides. Recently, a biologically compatible peptide (named PW3 with the sequence of NH2-Trp-Val-Trp-Val-Trp-Val-Lys-Lys-COOH) has been introduced as a good candidate for modification of carbon nanotubes due to its high affinity toward the exterior surface of these nano-carriers. In order to optimize the process of SWCNT peptide functionalization, the effects of chirality and diameter of SWCNTs as well as the temperature on PW3 adsorption were systematically investigated using molecular dynamics (MD) simulation. It was found that modification of chiral/zigzag SWCNT by PW3 peptide was more suitable compared with the armchair system due to the strong peptide-nanotube interactions and more water solubility at 310 K which can be well explained by microscopic structural investigations. Regarding the enhanced peptide-chiral nanotube interactions at the low temperature of 277 K, chiral nanotubes can be effective structures for SWCNT functionalization process at reduced temperatures. Our analysis indicated that disrupted PW3 and SWCNT hydration patterns and fewer internal interactions within the peptide could be responsible for the stronger peptide modification of SWCNT at higher temperatures. Additionally, "PW3/SWCNT" systems containing larger tube diameters formed more stable complexes owing to their effective surface area increment.

Density functional theory evaluation of pristine and BN-doped biphenylene nanosheets to detect HCN.

Hydrogen cyanide (HCN) adsorption on pristine and B-N doped biphenylene nanosheets was investigated by means of density functional theory calculations. According to biphenylene geometry, all distinct possible B-N substitutions were designed. Adsorption energy and electronic structure at the level of M062X/6-31 g (d,p) theory were computed for all possible geometries. Our results reveal that pristine biphenylene nanosheet is not a suitable candidate for HCN detection. Also, for B-N doping, the sensitivity of the nanosheet depends on the B-N doped configuration. One of these derivative structures shows higher sensitivity to HCN adsorption due to the greater change in electronic properties. Moreover, atoms in molecules and natural bond orbital analysis were performed to obtain more in-depth knowledge about the adsorption mechanism. The range of energy for interaction between HCN and the nanosheets belongs to physical adsorption.

Influence of dendrimer surface chemistry and pH on the binding and release pattern of chalcone studied by molecular dynamics simulations.

Poly(amidoamine) (PAMAM) dendrimers are promising nanocarriers that can enhance the solubility of hydrophobic drugs. The surface chemistry of dendrimers is of great relevance as end groups of these nanocarriers can be easily modified to improve the bioavailability and sustained release of the cargo. Therefore, a molecular-level understanding of the host-guest interactions that can give both qualitative and quantitative information is particularly desirable. In this work, fully atomistic molecular dynamics simulations were used to study the association of a bioactive natural product, ie, chalcone, with amine-, acetyl-, and carboxyl-terminated PAMAM dendrimers at physiological and acidic pH environments. Amine- and carboxyl-terminated PAMAM dendrimers have an open microstructure at low pH that is not able to hold the ligand tightly, resulting in an unfavorable encapsulation of the chalcone molecule. In the case of acetyl-terminated dendrimer, chalcone molecule diffuses out of the dendritic cavities a few times during the simulation time and prefers to locate close to the surface of dendrimer. Average center of mass distance values at neutral pH showed that the chalcone molecule bounds firmly in the internal pockets of amine-, acetyl-, and carboxyl-terminated dendrimers and forms stable complexes with these nanovectors. The potential of mean force calculations showed that the release of the ligand from the dendrimers occurs at a controlled rate in the body.

Bare surface of gold nanoparticle induces inflammation through unfolding of plasma fibrinogen.

The surface of nanoparticles (NPs) get coated by a wide range of biomolecules, upon exposure to biological fluids. It is now being increasingly accepted that NPs with particular physiochemical properties have a capacity to induce conformational changes to proteins and therefore influence their biological fates, we hypothesized that the gold NP's metal surface may also be involved in the observed Fg unfolding and inflammatory response. To mechanistically test this hypothesis, we probed the interaction of Fg with gold surfaces using molecular dynamic simulation (MD) and revealed that the gold surface has a capacity to induce Fg conformational changes in favor of inflammation response. As the integrity of coatings at the surface of ultra-small gold NPs are not thorough, we also hypothesized that the ultra-small gold NPs have a capacity to induce unfolding of Fg regardless of the composition and surface charge of their coatings. Using different surface coatings at the surface of ultra-small gold NPs, we validated this hypothesis. Our findings suggest that gold NPs may cause unforeseen inflammatory effects, as their surface coatings may be degraded by physiological activity.

Atomistic computer simulations on multi-loaded PAMAM dendrimers: a comparison of amine- and hydroxyl-terminated dendrimers.

Poly(amidoamine) (PAMAM) dendrimers have been extensively studied as delivery vectors in biomedical applications. A limited number of molecular dynamics (MD) simulation studies have investigated the effect of surface chemistry on therapeutic molecules loading, with the aim of providing insights for biocompatibility improvement and increase in drug loading capacity of PAMAM dendrimers. In this work, fully atomistic MD simulations were employed to study the association of 5-Fluorouracil (5-FU) with amine (NH2)- and hydroxyl (OH)-terminated PAMAM dendrimers of generations 3 and 4 (G3 and G4). MD results show a 1:12, 1:1, 1:27, and 1:4 stoichiometry, respectively, for G3NH2-FU, G3OH-FU, G4NH2-FU, and G4OH-FU complexes, which is in good agreement with the isothermal titration calorimetry results. The results obtained showed that NH2-terminated dendrimers assume segmented open structures with large cavities and more drug molecules can encapsulate inside the dendritic cavities of amine terminated dendrimers. However, OH-terminated have a densely packed structure and therefore, 5-FU drug molecules are more stable to locate close to the surface of the dendrimers. Intermolecular hydrogen bonding analysis showed that 5-FU drug molecules have more tendency to form hydrogen bonds with terminal monomers of OH-terminated dendrimers, while in NH2-terminated these occur both in the inner region and the surface. Furthermore, MM-PBSA analysis revealed that van der Waals and electrostatic energies are both important to stabilize the complexes. We found that drug molecules are distributed uniformly inside the amine and hydroxyl terminated dendrimers and therefore, both dendrimers are promising candidates as drug delivery systems for 5-FU drug molecules.

DFT, QTAIM, and NBO studies on the trimeric interactions in the protrusion domain of a piscine betanodavirus.

Crystal structure of the protrusion domain (P-domain) of the grouper nervous necrosis virus (GNNV) shows the presence of three-fold trimeric protrusions with two asymmetrical calcium cations along the non-crystallographic three-fold axis. The trimeric interaction natures of the interacting residues and the calcium cations with the neighboring residues within the trimeric interface have been studied by the quantum theory of atoms in molecules (QTAIM) and natural bond orbital (NBO) analyses in the framework of the density-functional theory (DFT) approach. The results revealed that residues Leu259, Val274, Trp280, and Gln322 of subunit A, Arg261, Asp275, Ala277, and Gln322 of subunit B, Leu259, Asp260, Arg261, Ala277, Val278, and Leu324 of subunit C are the main residues involved in the trimeric interactions. Charge-dipole, dipole-dipole, and hydrogen bonding interactions make the significant contributions to these trimeric interactions. Among different interacting residues within trimeric interface, residue pair Arg261 B-Leu259C forms the strongest hydrogen bond inside the interface between subunits B and C. It was also found that calcium cations interact with residues Asp273, Val274, and Asp275 of subunits A, B, and C through charge-charge and charge transfer interactions.

DFT Studies of NH-Cl Hydrogen Bond of Amino Acid Hydrochloride Salts in Ion Channels.

Quantum chemical calculations were made, to study NH-Cl hydrogen bonds of two amino acid hydrochloride salts called alanine and threonine. The Nuclear Magnetic Resonance and Nuclear Quadrupole Resonance parameters for nitrogen and chlorine were calculated via four functionals such as, B3LYP, M062X, M06L, and CAM-B3LYP and by applying the 6-311++G(d,p) basis set. One of the functionals produced more accurate results. Geometry optimization was performed using the M062X/6-31++G(d,p) method, and Natural Bond Orbitals analysis was performed by applying the M062X/6-311++G(d,p) level. This study examined Nuclear Magnetic Resonance and Nuclear Quadrupole Resonance parameters with changes in structure from monomer to pentamer and investigated correlations between Natural Bond Orbitals parameters and Nuclear Magnetic Resonance or Nuclear Quadrupole Resonance parameters. The Natural Bond Orbitals parameters were used to investigate changes in structural parameters along with crystal development.

A theoretical study on the characteristics of the intermolecular interactions in the active site of human androsterone sulphotransferase: DFT calculations of NQR and NMR parameters and QTAIM analysis.

A theoretical study at the level of density functional theory (DFT) was performed to characterize noncovalent intermolecular interactions, especially hydrogen bond interactions, in the active site of enzyme human androsterone sulphotransferase (SULT2A1/ADT). Geometry optimization, interaction energy, (2)H, (14)N, and (17)O electric field gradient (EFG) tensors, (1)H, (13)C, (17)O, and (15)N chemical shielding (CS) tensors, Natural Bonding Orbital (NBO) analysis, and quantum theory of atoms in molecules (QTAIM) analysis of this active site were investigated. It was found that androsterone (ADT) is able to form hydrogen bonds with residues Ser80, Ile82, and His99 of the active site. The interaction energy calculations and NBO analysis revealed that the ADT molecule forms the strongest hydrogen bond with Ser80. Results revealed that ADT interacts with the other residues through electrostatic and Van der Waals interactions. Results showed that these hydrogen bonds influence on the calculated (2)H, (14)N, and (17)O quadrupole coupling constants (QCCs), as well as (1)H, (13)C, (17)O, and (15)N CS tensors. The magnitude of the QCC and CS changes at each nucleus depends directly on its amount of contribution to the hydrogen bond interaction.

Interplay between tetrel and triel bonds in RC6H4CN⋯MF3CN⋯BX3 complexes: A combined symmetry-adapted perturbation theory, Møller-Plesset, and quantum theory of atoms-in-molecules study.

Intermolecular ternary complexes composed of: (1) the centrally placed trifluoroacetonitrile or its higher analogs with central carbon exchanged by silicon or germanium (M = C, Si, Ge), (2) the benzonitrile molecule or its para derivatives on one side, and (3) the boron trifluoride of trichloride molecule (X = F, Cl) on the opposite side as well as the corresponding intermolecular tetrel- and triel-bonded binary complexes, were investigated by symmetry-adapted perturbation theory (SAPT) and the supermolecular Møller-Plesset method (MP2) at the complete basis set limit for optimized geometries. A character of interactions was studied by quantum theory of atoms-in-molecules (QTAIM). A comparison of interaction energies and QTAIM bond descriptors for dimers and trimers reveals that tetrel and triel bonds increase in their strength if present together in the trimer. For the triel-bonded complex, this growth leads to a change of the bond character from closed-shell to partly covalent for Si or Ge tetrel atoms, so the resulting bonding scheme corresponds to a preliminary stage of the SN2 reaction. Limitations of the Lewis theory of acids and bases were shown by its failure in predicting the stability order of the triel complexes. The necessity of including interaction energy terms beyond the electrostatic component for an elucidation of the nature of σ- and π-holes was presented by a SAPT energy decomposition and by a study of differences in monomer electrostatic potentials obtained either from isolated monomer densities, or from densities resulting from a perturbation with the effective field of another monomer.

Structure and Energetics of Complexes of B12N12 with Hydrogen Halides-SAPT(DFT) and MP2 Study.

Molecular complexes of a fullerene analogue B12N12 with hydrogen halides (HCl, HBr, and HI) were studied with symmetry-adapted perturbation theory with density-functional theory applied for a description of monomers (SAPT(DFT)), Møller-Plesset theory to the second order (MP2), and its spin-component-scaled variant (SCS-MP2) in a limit of a complete basis set. For each halide five symmetry-distinct minimum structures of the complex have been found on the potential energy hypersurface, with interaction energies ranging from -6 to -18 kJ/mol. The natural bond orbital and the atom-in-molecules analysis of noncovalent bonds resulted in a division of these configurations into three categories: hydrogen-bonded, halogen-bonded, and those of a mixed type, involving simultaneously a hydrogen bonding and a π-hole bonding between halogen and boron atoms. A comparison of various approaches for the calculation of interaction energies shows that the SCS-MP2 supermolecular method gives results which are in a close agreement with SAPT(DFT), while the MP2 interaction energies are systematically more negative than the SAPT values. The ability of the B12N12 nanocage to bind hydrogen halides through several active sites on its surface puts under question the selectivity of the binding necessary in crystal engineering, especially for the hydrogen bromide and hydrogen iodide cases, which show small differences in stabilization energies for their minimum structures. The directionality of noncovalent bonds is explained on grounds of the anisotropy of some SAPT components, like electrostatics and induction, as well as by the σ-hole and π-hole models.

Theoretical investigation on the selective detection of SO2 molecule by AlN nanosheets.

Theoretical calculations focused on the ability of an AlN nanosheet to detect O(3) and SO(2) molecules based on the dispersion corrected B3LYP (B3LYP-D) and B97D density functionals. Equilibrium geometries, stabilities, and the electronic properties of O(3) and SO(2) adsorptions on the surface of an AlN sheet were explored. The adsorption energies were calculated to be about -17.80 and -21.51 kcal mol(-1) at B3LYP-D level for O(3) and SO(2) corresponding to the most stable configurations, respectively. It was shown that the electrical conductance of the AlN sheet may be increased after the SO(2) adsorption, being somewhat insensitive to the O(3) adsorption. Thus, the AlN sheet may selectively detect SO(2) molecules in the presence of O(3) molecules.

DFT studies of acrolein molecule adsorption on pristine and Al-doped graphenes.

The ability of pristine graphene (PG) and Al-doped graphene (AlG) to detect toxic acrolein (C3H4O) was investigated by using density functional calculations. It was found that C3H4O molecule can be adsorbed on the PG and AlG with adsorption energies about -50.43 and - v30.92 kcal mol(-1) corresponding to the most stable configurations, respectively. Despite the fact that interaction of C3H4O has no obvious effects on the of electronic properties of PG, the interaction between C3H4O and AlG can induce significant changes in the HOMO/LUMO energy gap of the sheet, altering its electrical conductivity which is beneficial to sensor designing. Thus, the AlG may be sensitive in the presence of C3H4O molecule and might be used in its sensor devices. Also, applying an external electric filed in an appropriate orientation (almost stronger than 0.01 a.u.) can energetically facilitate the adsorption of C3H4O molecule on the AlG.

Covalent hybridization of CNT by thymine and uracil: a computational study.

We have investigated the electronic and structural properties of covalent functionalization of the tip of (5,0) carbon nanotube (CNT) by di-keto and keto-enol forms of thymine (T) and uracil (U) nucleobases. Density functional theory (DFT) calculations have been performed to optimize the investigated structures and to calculate the properties such as dipole moment, bond length, band gap, total energy, binding energy and quadrupole coupling constant. The results indicated that, due to the functionalization of CNT by T and U, the hybrids exhibit new properties in which they are similar in both types of CNT-T and CNT-U hybrids.

Characterization of cooperative effects in linear alpha-glycylglycine clusters.

The aspects of N-H...O=CNH, N-H...O=CO and C-H...O=CNH interactions are analyzed by applying ab initio and DFT methods as well as Bader theory. We investigated geometry, binding energies, (17)O, (15)N chemical shift tensors, and Atoms in Molecules (AIM) properties of alpha-glycylglycine (alpha-glygly) clusters, via MP2, B3LYP and PW91(XC) methods. Dimer stabilization energies and equilibrium geometries are studied in various levels of theory. MP2 and DFT calculations reveal that for alpha-glygly clusters, stability of N-H...O and C-H...O hydrogen bonds are enhanced significantly as a result of cooperativity effects. Furthermore, a covalent nature is also detected for some hydrogen bondings. The n-dependent trend of (17)O and (15)N chemical shift tensors was reasonably correlated with cooperative effects in hydrogen-bond interactions. Regarding the various N-H...O=CNH, N-H...O=CO and C-H...O=CNH hydrogen bondings, capability of the alpha-glygly clusters for electron localization at the N-H...O and C-H...O bond critical points, depends on the cluster size. This leads to cooperative changes in the hydrogen-bond length and strength as well as (17)O and (15)N chemical shift tensors.

A theoretical study of repeating sequence in HRP II: a combination of molecular dynamics simulations and (17)O quadrupole coupling tensors.

Histidine rich protein II derived peptide (HRP II 169-182) was investigated by molecular dynamics, MD, simulation and (17)O electric field gradient, EFG, tensor calculations. MD simulation was performed in water at 300 K with alpha-helix initial structure. It was found that peptide loses its initial alpha-helix structure rapidly and is converted to random coil and bent secondary structures. To understand how peptide structure affects EFG tensors, initial structure and final conformations resulting from MD simulations were used to calculate (17)O EFG tensors of backbone carbonyl oxygens. Calculations were performed using B3LYP method and 6-31+G basis set. Calculated (17)O EFG tensors were used to evaluate quadrupole coupling constants, QCC, and asymmetry parameters, eta(Q). Difference between the calculated QCC and eta(Q) values revealed how hydrogen-bonding interactions affect EFG tensors at the sites of each oxygen nucleus.

Theoretical 14N nuclear quadrupole resonance parameters for sulfa drugs: sulfamerazine and sulfathiazole.

A density functional theory investigation was carried out to characterize (14)N electric field gradient tensors, EFG, in crystalline sulfamerazine and sulfathiazole. To include hydrogen-bonding effects in the calculations, the most probable interacting molecules with the target were considered as tetrameric and pentameric clusters, respectively. The calculated EFG tensors were used to evaluate nuclear quadrupole coupling tensors (chi(ii)) and asymmetry parameters (eta(Q)) for the target molecule in the clusters. Results are in satisfactory agreement with the experimental data. The EFG calculations reveal different contributions of nitrogen atoms in hydrogen-bonding network of the sulfamerazine and sulfathiazole. Moreover, based on the results obtained via atoms in molecules (AIM) analyses, an acceptable linear relation between (14)N nuclear quadrupole coupling constants and charge density values at N-H...N and N-H...O bond critical points, rho(b)(r(cp)), is observed.