Simulations on the possibility of formation of complexes between fluorouracil drug and cucurbit[n]urils: ab initio van der Waals DFT study

The binding geometry of fluorouracil/cucurbit[n]urils (CB[n]s) complexes with n?=?5–8 is investigated using the first-principles van der Waals density functional (vdW-DF) method, involving full geometry optimization. Such host-guest complexes are typically calculated using conventional DFT method, which significantly underestimates non-local dispersion forces (or vdW contributions) and therefore affects interactions between respected entities. We address here the role of vdW forces for the fluorouracil and CB[n]s molecules which can form directional hydrogen bonds with each other. It was found that the inclusion of dispersion interactions significantly affects the host-guest binding properties and the hydrogen bonding between the molecules provides the main binding mechanism, while results in the same geometries for the considered complexes. The 0.84 eV binding energy, for the thermodynamically favorable state, reveals that the interaction of fluorouracil with CB[n]s is an exothermic interaction and typical for strong hydrogen bonding. Furthermore, we have investigated the binding nature of these host-guest systems in aqueous solution with ab initio MD simulations adopting vdW-DF method. These findings afford evidence for the applicability of the vdW-DF approach and provide a realistic benchmark for the investigation of the host-guest complexes.

Ab initio molecular dynamics simulation on the formation process of He@C60 synthesized by explosion

The applications of endohedral non-metallic fullerenes are limited by their low production rate. Recently, an explosive method developed in our group shows promise to prepare He@C₆₀ at fairly high yield, but the mechanism of He inserting into C₆₀ cage at explosive conditions was not clear. Here, ab initio molecular dynamics analysis has been used to simulate the collision between C₆₀ molecules at high-temperature and high-pressure induced by explosion. The results show that defects formed on the fullerene cage by collidsion can effectively decrease the reaction barrier for the insertion of He into C₆₀, and the self-healing capability of the defects was also observed.

Theoretical study on aluminum carbide endohedral fullerene-Al4C@C80

The possibility of a new endohedral fullerene with a trapped aluminum carbide cluster, Al₄C @C₈₀-I _h , was theoretical investigated. The geometries and electronic properties of it were investigated using density functional theory methods. The Al₄C unit formally transfers six electrons to the C₈₀ cage which induces stabilization of Al₄C@C₈₀. A favorable binding energy, relatively large HOMO-LUMO gap, electron affinities and ionization potentials suggested the Al₄C@C₈₀ is rather stable. The analysis of vertical ionization potential and vertical electron affinity indicate Al₄C@C₈₀ is a good electron acceptor.

The effect of C-vacancy on hydrogen storage and characterization of H2 modes on Ti functionalized C60 fullerene A first principles study

Density functional theory calculations were performed to examine the effect of a C vacancy on the physisorption of H₂ onto Ti-functionalized C₆₀ fullerene when H₂ is oriented along the x-, y-, and z-axes of the fullerene. The effect of the C vacancy on the physisorption modes of H₂ was investigated as a function of H₂ binding energy within the energy window (?0.2 to ?0.6 eV) targeted by the Department of Energy (DOE), and as functions of a variety of other physicochemical properties. The results indicate that the preferential orientations of H₂ in the defect-free (i.e., no C vacancy) C₆₀TiH₂ complex are along the x- and y-axes of C₆₀ (with adsorption energies of ?0.23 and ?0.21 eV, respectively), making these orientations the most suitable ones for hydrogen storage, in contrast to the results obtained for defect-containing fullerenes. The defect-containing (i.e., containing a C vacancy) C₅₉TiH₂ complex do not exhibit adsorption energies within the targeted energy range. Charge transfer occurs from Ti 3d to C 2p of the fullerene. The binding of H₂ is dominated by the pairwise support–metal interaction energy E(i)^Cn...Ti, and the role of the fullerene is not restricted to supporting the metal. The C vacancy enhances the adsorption energy of Ti, in contrast to that of H₂. A significant reduction in the energy gap of the pristine C₆₀ fullerene is observed when TiH₂ is adsorbed by it. While the C _n fullerene readily participates in nucleophilic processes, the adjacent TiH₂ fragment is available for electrophilic processes.

Theoretical study on cooperative effects between X⋯N and X⋯Carbene halogen bonds (X = F,Cl,Br and I)

Quantum chemical calculations are performed to study the interplay between halogen?nitrogen and halogen?carbene interactions in NCX?NCX?CH₂ complexes, where X?=?F, Cl, Br and I. Molecular geometries and interaction energies of dyads and triads are investigated at the MP2/aug-cc-pVTZ level of theory. It is found that the X?N and X?C_carbene interaction energies in the triads are larger than those in the dyads, indicating that both the halogen bonding interactions are enhanced. The estimated values of cooperative energy E _coop are all negative with much larger E _coop in absolute value for the systems including iodine. The nature of halogen bond interactions of the complexes is analyzed using parameters derived from the quantum theory atoms in molecules methodology and energy decomposition analysis.

Synthesis and biological evaluation of cationic fullerene quinazolinone conjugates and their binding mode with modeled Mycobacterium tuberculosis hypoxanthine-guanine phosphoribosyltransferase enzyme

The present work reports a series of novel cationic fullerene derivatives bearing a substituted-quinazolinone moiety as a side arm. Fullerene-quinazolinone conjugates synthesized using the 1,3-dipolar cycloaddition reaction of C₆₀ with azomethine ylides generated from the corresponding Schiff bases of substituted quinazolinone were characterized by elemental analysis, FT-IR, ¹H NMR, ¹³C NMR and ESI-MS and screened for their antibacterial activity against Mycobacterium tuberculosis (H ₃₇ Rv strain). All the compounds exhibited significant activity with the most effective having MIC in the range of 1.562–3.125 μg/mL. Compound 9f exhibited good biological activity compared to standard drugs. We developed a computational strategy based on the modeled M. tuberculosis hypoxanthine-guanine phosphoribosyltransferase (HGPRT) using homology modeling techniques and studied its binding pattern with synthesized fullerene derivatives. We then explored the surface geometry of the protein to place the cage adjacent to the active site while optimizing its quinazolinone side arm to establish H bonding with active site residues.

Simple benzene derivatives adsorption on defective single-walled carbon nanotubes: a first-principles van der Waals density functional study

We have investigated the interaction between open-ended zig-zag single-walled carbon nanotube (SWCNT) and a few benzene derivatives using the first-principles van der Waals density functional (vdW-DF) method, involving full geometry optimization. Such sp ²-like materials are typically investigated using conventional DFT methods, which significantly underestimate non-local dispersion forces (vdW interactions), therefore affecting interactions between respected molecules. Here, we considered the vdW forces for the interacting molecules that originate from the interacting π electrons of the two systems. The ?0.54 eV adsorption energy reveals that the interaction of benzene with the side wall of the SWCNT is typical of the strong physisorption and comparable with the experimental value for benzene adsorption onto the graphene sheet. It was found that aromatics are physisorbed on the sidewall of perfect SWCNTs, as well as at the edge site of the defective nanotube. Analysis of the electronic structures shows that no orbital hybridization between aromatics and nanotubes occurs in the adsorption process. The results are relevant in order to identify the potential applications of noncovalent functionalized systems.

A theoretical study on the halogen bonding interactions of C6F5I with a series of group 10 metal monohalides

The halogen bonding interactions between C₆F₅I and a series of transition metal monohalides trans-[M(X)(2-C₅NF₄)-(PR₃)₂] (M = Ni, Pd, Pt; X = F, Cl, Br; R = Me, Cy) have been studied with quantum chemical calculations. Optimized geometries of the halogen bonding complexes indicate that angles C₁-I···X are basically linear (178–180°) and angles I···X-M mainly range from 90 to 150°. The strength of these metal-influenced halogen bonds alters with different metal centers, metal-bound halogen atoms and the substitutes on phosphine ligands. Electrostatic potential and natural bond orbital analysis show that both of the electrostatic and orbital interactions make a contribution to the formation of halogen bonds, while the electrostatic term plays a dominant role. AIM analysis suggests that, for trans-[M(F)(2-C₅NF₄)-(PR₃)₂] (M = Ni, Pd, Pt) monomers, the formed halogen bonding complexes are stabilized by local concentration of the charge of intermediate character, while for the metal monomers containing chlorine and bromine, a typical closed-shell interaction exist. These results prove that the structures and geometries of these halogen bonding complexes can be tuned by changing the halogen atoms and metal centers, which may provide useful information for the design and synthesis of new functional materials.

Dynamic motion of La atom inside the C74 (D 3h) cage: a relativistic DFT study

The interaction between lanthanum atom (La) and C₇₄ (D _3h) was investigated by all-electron relativistic density function theory (DFT). With the aid of the representative patch of C₇₄ (D _3h), we studied the interaction between C₇₄ (D _3h) and La and obtained the interaction potential. Optimized structures show that there are three equivalent stable isomers, with La located about 1.7 Å off center. There is one transition state between every two stable isomers. According to the minimum energy pathway, the possible movement trajectory of La atoms in the C₇₄ (D _3h) cage was explored. The calculated energy barrier for La atoms moving from the stable isomer to the transition state is 18.4 kcal mol^?1. In addition, the dynamic NMR spectra of La@C₇₄ according to the trajectory was calculated.

A B3LYP and MP2(full) theoretical investigation into the cooperativity effect between dihydrogen-bonding and H–M∙∙∙π (M = Li, Na, K) interactions among HF, MH with the π-electron donor C2H2, C2H4 or C6H6

The DFT-B3LYP/6-311++G(3df,2p) and MP2(full)/6-311++G(3df,2p) calculations were carried out on the binary complex formed by HM (M?=?Li, Na, K) and HF or the π-electron donor (C₂H₂, C₂H₄, C₆H₆), as well as the ternary system FH???HM???C₂H₂/C₂H₄/C₆H₆. The cooperativity effect between the dihydrogen-bonding and H–M???π interactions was investigated. The result shows that the equilibrium distances R _H???H and R _M???π in the ternary complex decrease and both the H???H and H–M???π interactions are strengthened when compared to the corresponding binary complex. The cooperativity effect of the dihydrogen bond on the H–M???π interaction is more pronounced than that of the M???π bond on the H???H interaction. Furthermore, the values of cooperativity effect follow the order of FH???HNa???π?>?FH???HLi???π?>?FH???HK???π and FH???HM???C₆H₆?>?FH???HM???C₂H₄?>?FH???HM???C₂H₂. The nature of the cooperativity effect was revealed by the analyses of the charge of the hydrogen atoms in H???H moiety, atom in molecule (AIM) and electron density shifts methods.

Relativistic theoretical studies on hydrogen bonds and the electronic structure of aqueous solvated bis(uranyl) complex: an insight into explicit and/or implicit solvent effects

To understand the chemical behavior of uranyl complexes in water, a bis-uranyl [(phen)(UO₂)(μ₂–F)(F)]₂ (A; phen?=?phenanthroline, μ₂?=?doubly bridged) and its hydrated form A?·?(H₂O)_n (n?=?2, 4 and 6) were examined using scalar relativistic density functional theory. The addition of water caused the phen ligands to deviate slightly from the U₂(μ₂–F)₂ plane, and red-shifts the U–F-terminal and U?=?O stretching vibrations. Four types of hydrogen bonds are present in the optimized hydrated A?·?(H₂O)_n complexes; their energies were calculated to fall within the range 4.37–6.77 kcal mol^-1, comparable to the typical values of 5.0 kcal mol^-1 reported for hydrogen bonds. An aqueous environment simulated by explicit and/or implicit models lowers and re-arranges the orbitals of the bis-uranyl complex.

Cyclo-hexa-peptides at the water/cyclohexane interface: a molecular dynamics simulation

Molecular dynamic (MD) simulations have been performed to study the behaviors of ten kinds of cyclo-hexa-peptides (CHPs) composed of amino acids with the diverse hydrophilic/hydrophobic side chains at the water/cyclohexane interface. All the CHPs take the “horse-saddle” conformations at the interface and the hydrophilicity/hydrophobicity of the side chains influences the backbones’ structural deformations. The orientations and distributions of the CHPs at the interface and the differences of interaction energies (ΔΔE) between the CHPs and the two liquid phases have been determined. RDF analysis shows that the H-bonds were formed between the O_C atoms of the CHPs’ backbones and H_w atoms of water molecules. N atoms of the CHPs’ backbones formed the H-bonds or van der Waals interactions with the water solvent. It was found that there is a parallel relationship between ΔΔE and the lateral diffusion coefficients (D _xy ) of the CHPs at the interface. The movements of water molecules close to the interface are confined to some extent, indicating that the dynamics of the CHPs and interfacial water molecules are strongly coupled.

DFT study of the mechanism of the reaction of aminoguanidine with methylglyoxal

Density functional theory calculations were used in the theoretical investigation of the adsorption properties of sumanene towards molecules considered as common air pollutants: CO, CO₂ and NH₃. The insignificant perturbation of sumanene after adsorption and the adsorption energies obtained indicate a physisorption mechanism. It was shown that, contrary to carbon nanotubes, sumanene is able to adsorb CO molecules, and that adsorption of CO₂ by sumanene is stronger than adsorption of CO₂ by C₆₀. To better understand the adsorption characteristics of sumanene, density of states and natural bond order analyses were performed, which showed that chemical interactions exist and that these are more important mostly on the convex side. Better adsorption properties were obtained for the concave side as adsorption is dictated by physisorption mechanisms due to the specific bowl-shaped geometry of sumanene, because of which more negative charge is located precisely on the concave side. Molecular electrostatic potential surfaces were also used in order to better locate the adsorption sites and gain additional details about adsorption.

Stability and isomerization of complexes formed by metal ions and cytosine isomers in aqueous phase

We present a systematic study of the stability of the formation of complexes produced by four metal ions (M^+/2+) and 14 cytosine isomers (C_n). This work predicts theoretically that predominant product complexes are associated with higher-energy C₄M^+/2+ and C₅M^+/2+ rather than the most stable C₁M^+/2+. The prediction resolves successfully several experimental facts puzzling two research groups. Meanwhile, in-depth studies further reveal that direct isomerization of C₁?C₄ is almost impossible, and also that the isomerization induced by either metalation or hydration, or by a combination of the two unfavorable. It is the single water molecule locating between the H1(?N1) and O2 of the cytosine that plays the dual roles of being a bridge and an activator that consequently improves the isomerization greatly. Moreover, the cooperation of divalent metal ion and such a monohydration actually leads to an energy-free C₁←C₄ isomerization in the gas phase. Henceforth, we are able to propose schemes inhibiting the free C₁←C₄ isomerization, based purely on extended hydration at the divalent metal ion.

A comparative study on carbon, boron-nitride, boron-phosphide and silicon-carbide nanotubes based on surface electrostatic potentials and average local ionization energies

A density functional theory study was carried out to predict the electrostatic potentials as well as average local ionization energies on both the outer and the inner surfaces of carbon, boron-nitride (BN), boron-phosphide (BP) and silicon-carbide (SiC) single-walled nanotubes. For each nanotube, the effect of tube radius on the surface potentials and calculated average local ionization energies was investigated. It is found that SiC and BN nanotubes have much stronger and more variable surface potentials than do carbon and BP nanotubes. For the SiC, BN and BP nanotubes, there are characteristic patterns of positive and negative sites on the outer lateral surfaces. On the other hand, a general feature of all of the systems studied is that stronger potentials are associated with regions of higher curvature. According to the evaluated surface electrostatic potentials, it is concluded that, for the narrowest tubes, the water solubility of BN tubes is slightly greater than that of SiC followed by carbon and BP nanotubes.

Deamination features of 5-hydroxymethylcytosine,a radical and enzymatic DNA oxidation product

Geometric consequences of electron delocalization were studied for all possible adenine tautomers in aqueous solution by means of ab initio methods {PCM(water)//DFT(B3LYP)/6-311+G(d,p)} and compared to those in the gas phase {DFT(B3LYP)/6-311+G(d,p)}. To measure the consequences of any type of resonance conjugation (π-π, n-π, and σ-π), the geometry-based harmonic oscillator model of electron delocalization (HOMED) index, recently extended to the isolated (DFT) and hydrated (PCM//DFT) molecules, was applied to the molecular fragments (imidazole, pyrimidine, 4-aminopyrimidine, and purine) and also to the whole tautomeric system. For individual tautomers, the resonance conjugations and consequently the bond lengths strongly depend on the position of the labile protons. The HOMED indices are larger for tautomers (or their fragments) possessing the labile proton(s) at the N rather than C atom. Solvent interactions with adenine tautomers slightly increase the resonance conjugations. Consequently, they slightly shorten the single bonds and lengthen the double bonds. When going from the gas phase to water solution, the HOMED indices increase (by less than 0.15 units). There is a good relation between the HOMED indices estimated in water solution and those in the gas phase for the neutral and ionized forms of adenine. Subtle effects, being a consequence of intramolecular interactions between the neighboring groups, are so strongly reduced by solvent that the relation between the HOMED indices and the relative energies for the neutral adenine tautomers seems to be better in water solution than in the gas phase.

DFT study on the reactions of ClO–/BrO– with RCl (R = CH3, C2H5, and C3H7) in gas phase

Gas-phase reactions of ClO^–/BrO^– with RCl (R = CH₃, C₂H₅, and C₃H₇) have been investigated in detail using the popular DFT functional BHandHLYP/aug-cc-pVDZ level of theory. As a result, our findings strongly suggest that the type of reaction is firstly initiated by a typical S_N2 fashion. Subsequently, two competitive substitution steps, named as S_N2-induced substitution and S_N2-induced elimination, respectively, would proceed before the initial S_N2 product ion-dipole complex separates, in which the former exhibits less reactivity than the latter. Those are consistent with relevant experimental results. Moreover, we have also explored reactivity difference for the title reactions in term of some factors derived from methyl group, p-π electronic conjugation, ionization energy (IE), as well as molecular orbital (MO) analysis.

Insights into the structural determinants for selective inhibition of nitric oxide synthase isoforms

Selective inhibition of the nitric oxide synthase isoforms (NOS) is a promising approach for the treatment of various disorders. However, given the high active site conservation among all NOS isoforms, the design of selective inhibitors is a challenging task. Analysis of the X-ray crystal structures of the NOS isoforms complexed with known inhibitors most often gives no clues about the structural determinants behind the selective inhibition since the inhibitors share the same binding conformation. Aimed at a better understanding of the structural factors responsible for selective inhibition of NOS isoforms we have performed MD simulations for iNOS, nNOS and eNOS complexed with N^ω-NO₂-L-Arg (1), and with the aminopyridine derivatives 2 and 3. The slightly better selectivity of 1 for nNOS may be assigned to the presence of extra charge–charge interactions due to its “extended” conformation. While the high affinity of 2 for iNOS can be explained by the formation of an iNOS-specific subpocket upon binding, the lack of affinity for eNOS is associated to a conformational change in Glu363. The strong van der Waals and electrostatic interactions between 3 and the active site of nNOS are most likely responsible for its higher affinity for this isoform. Owing to the elongated and narrow binding pocket of iNOS, the correct positioning of 3 over the heme group is difficult, which may account for its lower affinity toward this isoform. Brought together, our results might help to rationalize the design of selective NOS inhibitors.

GIAO-DFT-NMR characterization of fullerene-cucurbituril complex: the effects of the C<Subscript>60</Subscript>@CB[9] host-guest mutual interactions

Magnetic shielding constants for an isolated fullerene C₆₀, cucurbituril CB[9], and the host-guest complex C₆₀@CB[9] were calculated as a function of separation of the monomers. Our results in the gas phase and water indicate a significant variation of the magnetic properties for all atoms of the monomers in the complex and after liberation of fullerene C₆₀ from the interior of the CB[9] cavity. The interaction between the two monomers results in a charge transfer that collaborates with a redistribution of electron density to deshield the monomers.

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Graphical Abstract NMR spectroscopy alteration on C₆₀@CB[9] host-guest mutual interactions?

     

B30H8, B39H9 2−, B42H10, B48H10, and B72H12: polycyclic aromatic snub hydroboron clusters analogous to polycyclic aromatic hydrocarbons

Calculations performed at the ab initio level using the recently reported planar concentric π-aromatic B₁₈H₆ ²⁺(1) [Chen Q et al. (2011) Phys Chem Chem Phys 13:20620] as a building block suggest the possible existence of a new class of B_3n H _m polycyclic aromatic hydroboron (PAHB) clusters—B₃₀H₈(2), B₃₉H₉ ^2?(3), B₄₂H₁₀(4/5), B₄₈H₁₀(6), and B₇₂H₁₂(7)—which appear to be the inorganic analogs of the corresponding C _n H _m polycyclic aromatic hydrocarbon (PAHC) molecules naphthalene C₁₀H₈, phenalenyl anion C₁₃H₉ ^?, phenanthrene/anthracene C₁₄H₁₀, pyrene C₁₆H₁₀, and coronene C₂₄H₁₂, respectively, in a universal atomic ratio of B:C?=?3:1. Detailed canonical molecular orbital (CMO), adaptive natural density partitioning (AdNDP), and electron localization function (ELF) analyses indicate that, as they are hydrogenated fragments of a boron snub sheet [Zope RR, Baruah T (2010) Chem Phys Lett 501:193], these PAHB clusters are aromatic in nature, and exhibit the formation of islands of both σ- and π-aromaticity. The predicted ionization potentials of PAHB neutrals and electron detachment energies of small PAHB monoanions should permit them to be characterized experimentally in the future. The results obtained in this work expand the domain of planar boron-based clusters to a region well beyond B₂₀, and experimental syntheses of these snub B_3n H _m clusters through partial hydrogenation of the corresponding bare B_3n may open up a new area of boron chemistry parallel to that of PAHCs in carbon chemistry.