Cyclophosphamides as hypoxia-activated diffusible cytotoxins: A theoretical study

Cyclophosphamides have been in clinical use as anti-cancer drugs for a long time and much research has been directed towards reducing their side effects. Here we have performed a theoretical investigation into the possibility of designing bioreductive analogues of cyclophosphamides. Our calculations have employed semiempirical molecular orbital AM1-SM2 and PM3-SM3 calculations, as implemented in MOPAC 93, which include a modified Born method for the treatment of solvation. We have investigated the effect of bioreductive activation on the -elimination reaction that is central to the activation of cyclophosphamides. The approach was tested on two known bioreductive agents, including CB1954, and gave results in agreement with experiment. Non-local density functional calculations on CB1954 and its metabolites, including the radical anion, were in agreement with the semiempirical calculations. The calculations have identified a number of potentially novel bioreductive cyclophosphamides. In particular, our calculations identified compounds in which the initial one-electron reduction was not activating. Such compounds are likely to be more effective bioreductive agents, as the -elimination will not compete under oxic conditions with the important re-oxidation required for the protection of oxic tissue.     

A theoretical study of micro-domain formation in mixed lipid membranes

The thermodynamic stability of micro-clusters in a membrane built-up by charged and uncharged lipid molecules is discussed. A simple variational function is proposed in order to describe the essential structure of such lipid domains. Solvent-screened electrostatic repulsion between the lipid ionic head groups, short-range forces between the lipid hydrophobic taisl and entropic effects are taken into account. The stability conditions as well as the composition and the size of the lipid micro-domains are calculated and expressed as a function of molecular parameters for the membrane and its environment (for example, short-range forces, surface charge density of the lipid bilayer, ion concentration of the electrolyte solution in contact with the lipid membrane and temperature). As an application, the effect of micro-domain formation on the number of adsorbed ions on a charged lipid membrane has been calculated.     

Iminophosphanes: Unconventional Compounds of Main Group Elements

The large number of known stable compounds in which phosphorus has a low coordination number makes it clear that such compounds can no longer be regarded as “exotic” in main group chemistry. While the rich chemistry of P? C multiply bonded systems makes clear their affinity to their organic congeners, iminophosphanes in particular are also of increasing importance. The linkage of a phosphinidine fragment with an imine fragment via a multiple bond gives rise to a class of compounds with an unusually wide range of structural types. This in turn leads to a broad spectrum of chemical behavior which makes iminophosphanes extremely useful synthetic building blocks in organoelement chemistry.     

A theoretical study of carbon-carbon bond formation by a Michael-type addition

A theoretical study of the Michael-type addition of 1,3-dicarbonyl compounds to α,β-unsaturated carbonyl compounds has been performed in the gas phase by means of the AM1 semiempirical method and by density functional theory (DFT) calculations within the B3LYP and M06-2X hybrid functionals. A molecular model has been selected to mimic the role of a base, which is traditionally used as a catalyst in Michael reactions, an acetate moiety to modulate its basicity, and point charges to imitate the stabilization of the negative charge developed in the substrate during the reaction when taking place in enzymatic environments. Results of the study of six different reactions obtained at the three different levels of calculations show that the reaction takes place in three steps: in the first step the α proton of the acetylacetone is abstracted by the base, then the nucleophilic attack on the β-carbon of the α,β-unsaturated carbonyl compound takes place generating the negatively charged enolate intermediate, and finally the product is formed through a proton transfer back from the protonated base. According to the energy profiles, the rate limiting step corresponds to the abstraction of the proton or the carbon-carbon bond formation step, depending on substituents of the substrates and method of calculation. The effect of the substituents on the acidity of the α proton of the acetylacetone and the steric hindrance can be analyzed by comparing these two separated steps. Moreover, the result of adding a positive charge close to the center that develops a negative charge during the reaction confirms the catalytic role of the oxyanion hole proposed in enzyme catalysed Michael-type additions. Stabilization of the intermediate implies, in agreement with the Hammond postulate, a reduction of the barrier of the carbon-carbon bond formation step. Our results can be used to predict the features that a new designed biocatalyst must present to efficiently accelerate this fundamental reaction in organic synthesis.     

A theoretical study of the formation of phosphaacetylene by thermolysis of triallylphosphine

A theoretical study of the decomposition of triallylphosphine into phosphaacetylene at the B3LYP/6-311++G(3df,2p) level has shown that the most likely mechanism involves two retroene eliminations of propene leading to vinylphosphaacetylene. Two mechanisms can account for the formation of HCP from vinylphosphaacetylene, either by a 1,2 or a 1,3 hydrogen shift. The first pathway was found to be the most favored kinetically. It is quite similar to the pathway proposed for the thermal decomposition of vinylacetylene into acetylene in the shock tube.     

纤维素热解形成左旋葡聚糖机理的理论研究

采用密度泛函理论UB3LYP/6-31G(d)方法,对模型化合物纤维二糖热解反应机理进行了量子化学理论计算研究。设计了三种可能的热解反应途径,对各种反应的反应物、产物、中间体和过渡态的结构进行了能量梯度全优化,计算了不同温度下热解反应的标准热力学和动力学参数。计算结果表明,糖苷键均裂而形成两个自由基中间体IM₁a和IM₁b,吸收热量为321.26kJ/mol,中间体IM₁a经过渡态TS₁a进一步形成左旋葡聚糖P₁,反应势垒为202.72kJ/mol;与分步反应相比,纤维二糖经过渡态TS₂协同反应直接形成左旋葡聚糖P₁和吡喃葡萄糖P₂的反应势垒低于分步反应的总势垒,其反应势垒为377.54kJ/mol;H⁺的加入有利于糖苷键的断裂,断裂形成的中间体IM₃很难进一步反应形成左旋葡聚糖。     

Chalcanthrene-fullerene complexes: A theoretical study

In this work we have considered a series of 10 chalcanthrenes-fullerene complexes that were studied by the BLYP density functional theory (DFT) approach. A complete series of chalcanthrenes (C₁₂H₈XY, in which X, Y = O, S, Se, Te) where computed in several combinations in order to demonstrate the effect of structural changes on the electronic properties of the complexes under consideration. The optimized geometries, dissociation energies, and vibrational spectra of the chalcanthrenes-fullerene complexes are reported.     

Photochromic spironaphthoxazines: A theoretical study

Photochromic spironaphthoxazines and their open merocyanine forms were studied via semiempirical Hartree–Fock SCF quantum chemical calculations. The most stable of the merocyanine isomers were found to have a cis–trans–cis conformation and the zwitterionic form is, generally, more stable than is the quinoidal tautomer. The calculated activation energy for the thermal bleaching reaction is in good agreement with the experimental one.     

Effect of methyl hydrogen sulfate on the formation of sulfuric acid-ammonia clusters: A theoretical study

Methyl hydrogen sulfate (MHS) as a common nucleation precursor that has important effect on new particle formation (NPF). Liu et al. showed that MHS and sulfuric acid (SA) generation are competitive due to consumption of the common precursor SO₃, and the nucleation ability of SA is better than MHS. Thus, MHS inhibits the SA-DMA-based clusters formation particularly in regions with high [MO] (methanol) (Liu et al., Proc. Natl. Acad. Sci. U.S.A. 2019, 116, 24,966). However, in regions where [H₂O] is much higher than [MO] ([SA] > > [MHS]), the SO₃ consumed by the generation of less MHS will not significantly reduce the [SA], whether MHS still inhibits SA-A-based clusters formation and how MHS affects the growth pathways of MHS-SA-A-based clusters remains unclear. Hence, quantum chemistry calculations combining Atmospheric Cluster Dynamics Code (ACDC) are used to investigate the role of MHS in the SA-A-based system. Our conclusions show two different effects of MHS in NPF process: “inhibiting” in regions with high [MO] and “weakly facilitating” in regions with high [H₂O] and low [MO]. The growth pathways show that with the increasing [MHS], the role of MHS in NPF gradually changes from “transporter” to “participator”, and the contribution to the pathways increases from 7 to 85%. Our results contribute to understanding the NPF in low-temperature regions with different concentrations of MO and H₂O.     

Unusual bond formation in aspartic protease inhibitors: a theoretical study

The origin of the formation of the weak bond N|C...O involved in an original class of aspartic protease inhibitors was investigated by means of the electron localization function (ELF) and explicitly correlated wave-function (MRCI) analysis. The distance between the electrophilic C and the nucleophilic N centers appears to be controlled directly by the polarity and proticity of the medium. In light of these investigations, an unusual dative N-C bonding picture was characterized. Formation of this bond is driven by the enhancement of the ionic contribution C(+)-O(-) induced mainly by the polarization effect of the near N lone pair, and to a lesser extent by a weak charge delocalization N-->CO. Although the main role of the solvating environment is to stabilize the ionic configuration, the protic solvent can enhance the C(+)-O(-) configuration through a slight but cumulative charge transfer towards water molecules in the short N-C distance regime. Our revisited bond scheme suggests the possible tuning of the N-CO interaction in the design of specific inhibitors.     

Synthesis and Coordination Chemistry of Iminophosphanes

Iminophosphanes are a new group of 1,3‐P,N‐ligands, readily obtainable from secondary phosphanes and nitrilium ions, having a tunable N‐donor site by means of varying the imine substituents. These ligands give, in high yields, monodentate gold complexes and bidentate rhodium and iridium complexes. Crystal structures are reported for both the ligands and the complexes.     

Graphdiyne as a novel nonactive anode for wastewater treatment: A theoretical study

Electrochemical oxidation of water to produce highly reactive hydroxyl radicals (OH) is the dominant factor that accounts for the organic compounds removal efficiency in water treatment. As an emerging carbon-based material, the investigation of electrocatalytic of water to produce OH on Graphdiyne (GDY) anode is firstly evaluated by using first-principles calculations. The theoretical calculation results demonstrated that the GDY anode owns a large oxygen evolution reaction (OER) overpotential (η^OER = 1.95 V) and a weak sorptive ability towards oxygen evolution intermediates (HO*, not OH). The high Gibbs energy change of HO* (3.18 eV) on GDY anode makes the selective production of OH (ΔG = 2.4 eV) thermodynamically favorable. The investigation comprises the understanding of the relationship between OER to electrochemical advanced oxidation process (EAOP), and give a proof-of-concept of finding the novel and robust environmental EAOP anode at quantum chemistry level.     

Gas-phase acidity, bond dissociation energy and enthalpy of formation of fluorine-substituted benzenes: A theoretical study

A variety of theoretical methods have been used to study the gas-phase acidity of benzene and its eleven fluorine-substituted derivatives: fluorobenzene, three isomers of difluorobenezene, three isomers of trifluorobenzene, three isomers of tetrafluorobenzene and 1,2,3,4,5-pentafluorobenzene. The high-level ab initio methods, G3//B3-LYP and CBS-QB3, are shown to reproduce experimental data to within an average of 1.9 and 1.4 kcal mol⁻¹, respectively. Of the lower-cost methods studied, M05-2X and MP2 showed the best overall performance with mean absolute deviations of just 1.2 and 1.1 kcal mol⁻¹, respectively. The effect of substitution and position on the acidity of the protons in the various compounds are studied and the structure-reactivity trends in these heterolytic C-H bond dissociation energies (BDEs) are compared with the corresponding homolytic C-H BDEs for the same species.     

离子对生成反应截面的量子散射理论研究

将Miller的S-矩阵变分法推广到离子对生成反应动力学的研究。M＋X~2→M^+＋X~2^-反应体系包括共价态(M＋X~2)和离子态(M^+＋X~2^-)两个势能面及其交叉效应,本文在此两态模型下导出了生成截面公式。在矩阵元计算中,平动波函数采用分布Gauss基作展开。作为上述公式的应用,对Cs＋O~2→Cs^+＋O~2^-反应体系作了数值计算并取得了满意结果。     

Cyclododecane and cyclotridecane complexes with cobalt as potent histidine chelators: A theoretical study

Density functional theory calculations have been employed to study the interaction between cyclododecane and cyclotridecane derivatives complexing cobalt and interacting with histidine. The results suggest that some of these derivatives have high molecular affinities toward histidine, higher than in the commonly used iminodiacetate–cobalt system. Those derivatives may become new, potent chelators for use in the immobilized-metal-ion-affinity chromatography to immobilize and/or purify peptides and proteins.     

p-benzoquinone-benzene clusters as potential nanomechanical devices: a theoretical study

The equilibrium structures and binding energies of the benzene complexes of p-benzoquinones (PBQ) and its negatively charged anionic species (PBQ- and PBQ2-) have been investigated theoretically using second-order M?ller-Plesset calculations. While neutral p-benzoquinone-benzene clusters (PBQ-Bz) prefer to have a parallel displaced geometry (P-c), CH...pi interactions (T-shaped geometries) prevail in the di-anionic PBQ-benzene (PBQ2- -Bz) complexes (T-e2-). Studies on dianionic p-benzoquinone-benzene clusters showed that two nonbonded intermolecular interactions compete in the most stable conformation. One is H-bonding interaction (C-H...O type) between carbonyl oxygen of p-benzoquinone and one of the hydrogen atoms of benzene, and the other is a pi-H interaction between pi-electron cloud of PBQ2- and another hydrogen atom of benzene. Blueshifted H-bonds were observed in T-shaped clusters. The changes in the geometrical preference of PBQ-Bz complex upon addition of electrons would be useful in designing optimized molecular mechanical devices based on the edge-to-face and face-to-face aromatic interactions.     

Alternant boron nitride cages: A theoretical study

Heteroatomic cages (B_N/2N_N/2) with borons and nitrogens fully replacing alternant sets of carbons in cages are built graph-theoretically and investigated via the semiempirical MNDO Hamiltonian. The comparison with their parent carbon cages C_N is made in terms both of electronic and of geometric changes. Infinite classes first of octahedral symmetry and second of hexagonal-bipyramidal symmetry fullerenoid cages are considered in detail. The difference in the electronegativities for boron and nitrogen implies the opening of HOMO-LUMO gaps for alternant BN clusters. In general, the borons prefer planar geometry (sp² hybridization) while the nitrogens prefer pyramidalization (sp³ hybridization). © 1997 John Wiley & Sons, Inc.     

A theoretical study of the heats of formation of some small molecules using non-empirical wavefunctions

Total energies, obtained from non-empirical LCAO-MO-SCF calculations on a series of reactions involving only closed-shell molecules and ions, have been used to calculate the heats of formation H ₂₉₈ ⁰ of a large number of small molecules. The Double- basis set calculations, after empirical corrections for inadequacies in the basis set and systematic errors found in all calculations involving oxygen and carbon atoms, usually predict the heats of formation within 10 kcal/mole of the experimental value. A series of similar calculations predicts the heats of formation of some negative ions for which experimental values are either not available or are unreliable.     

Reaction of propionitrile with methylidyne: A theoretical study

The results of a CCSD(T)-F12/cc-pVTZ-f12//ωB97XD/cc-pVTZ quantum-chemical study of the potential energy surface (PES) for the reaction of propionitrile with methylidyne are combined with Rice-Ramsperger-Kassel-Marcus (RRKM) calculations of the reaction rate constants and product branching ratios in the deep space conditions corresponding to the zero-pressure limit at various collision energies. The most energetically favorable reaction pathways have been identified. The reaction outcome has been shown to strongly depend on the branching in the entrance reaction channel, between CH additions and insertions into various C-H and C-C bonds. For instance, CH addition to the N atom predominantly leads to 3H-pyrrole + H (p9), with CH₂NC + C₂H₄ (p2) also being a significant product. CH addition to the triple C≡N bond mostly results in 2-methylene-2H-azirine + CH₃ (p13), whereas CH insertions into C-H bonds in the CH₃ and CH₂ groups of propionitrile form CH₂CN + C₂H₄ (p1) and CH₂CHCN + CH₃ (p7) respectively. Less likely CH insertions into single C-C bonds yield CH₃CHCHCN + H (p5) and CH₂CHCH₂CN + H (p8). The results indicate that the methylidyne + propionitrile reaction may represent a critical step toward the formation of heterocyclic N-containing molecules in the interstellar medium and in planetary atmospheres.     

The formation of Lewis acid/base stabilised phosphanyltrielanes - A theoretical and experimental study

Theoretical investigations on the thermochemistry and the reaction mechanism of the formation of Lewis acid/base stabilised phosphanyltrielanes D · H₂EPH₂ · A (D = Lewis base, A = Lewis acid) were conducted. The reactions of EH₃ · D with A · PH₃ to form D · H₂EPH₂ · A and H₂ (E = B, Al, Ga; D = NH₃; A = BH₃, Cr(CO)₅) are all exothermic, regardless of whether donors and acceptors are present or absent. The lithium chloride elimination reactions between EH₂Cl · D and A · PH₂Li to give D · H₂EPH₂ · A and LiCl are endothermic for donor/acceptor stabilised compounds, if formation of gaseous LiCl is considered. If solid lithium chloride is considered all reactions are strongly exothermic. Studies of the transition state for H₂-elimination reactions between EH₃ · D and A · PH₃ to yield D · H₂EPH₂ · A and H₂ were only successful for E = Al, Ga. In these cases the reaction proceeds via a transition state featuring a five or six-coordinate group 13 element. Different donor molecules do not influence the activation energy of such H₂-elimination reactions, but nevertheless they have an effect on the reaction energy. The synthesis of the Cr(CO)₅ substituted phosphanyltrielanes [(CO)₅Cr(H₂PBH₂ · NMe₃)] (3a) and [(CO)₅Cr(H₂PAlH₂ · NMe₃)] (3b), as well as of the dinuclear complex [(CO)₈Cr₂(μ-HPBH₂ · NMe₃)₂] (4) are described, the latter as a subsequent reaction product of the photolysis of 3a. All compounds were characterised spectroscopically and by X-ray structure analysis.