On the Stereochemistry of the NH Bond Activation of Ammonia or Amines by Disilenes: Predictability.

The stereochemistry of the addition of NH3 to the stereoisomers of 1,2-di-tert-butyl-1,2-bis(2,4,6-triisopropylphenyl)disilene (Z-5 or E-5) is 100 % stereospecific giving two isomeric disilylamines 6 and 7, respectively, derived from syn-addition to the stereoisomeric disilenes. Variable time normalization analysis studies of the reaction of tetramesityldisilene (3) with isopropylamine (i PrNH2 ) revealed that the order in both amine and disilene is 1. The kinetic isotope effect for the addition of i PrNH2 /i PrND2 to tetramesityldisilene was determined to be 3.04±0.06 at 298 K, a primary KIE, indicating that the proton is transferred in the rate determining step. Competition studies between the addition of PrNH2 and i PrNH2 to tetramesityldisilene resulted in the exclusive formation of the PrNH2 adduct consistent with a nucleophilic addition. Computational studies of the mechanism of the addition of ammonia to E-5 revealed the lowest energy pathway involves the formation of the donor adduct derived from syn-addition, followed by intramolecular syn-transfer of the proton. The formation of the donor adduct is the rate determining step. The results of this study, together with previous studies on the addition of ammonia and amines to disilenes, allow for a refinement of our understanding of the mechanism of this important fundamental reaction in disilene chemistry, and allow us to understand our ability to reliably predict the stereochemical outcomes of future NH σ-bond activation reactions.

Norbornene based-sulfide-stabilized silylium ions: synthesis, structure and application in catalysis.

A norbornene-based sulfide stabilized silylium ion 4 has been synthesized. The S-Si interaction was studied in solution and in the solid state by NMR spectroscopy and X-ray diffraction analysis as well as DFT calculations. Unlike the previously reported phosphine-stabilized silylium ion VII, behaving as a Lewis pair, calculations predict that 4 should behave as a Lewis acid toward acrylate derivatives. Indeed, the base-stabilized silylium ion 4 has emerged as an easy-to-handle silylium ion-based Lewis acid catalyst, particularly for the Diels-Alder cycloaddition, with poorly reactive dienes, and hydrodefluorination reactions.

NH bond activation of ammonia and amines by ditetrelenes: key insights into the stereochemistry of nucleophilic addition.

The NH bond activation of ammonia, primary and secondary amines by tetramesityldisilene and -digermene was investigated. In each case, a disilyl- or digermylamine was formed as the only product of amine addition. The mechanism of the addition of ammonia to tetramesityldisilene was computed and revealed a three-step reaction pathway: formation of the anti-ammonia-disilene adduct, inversion at the ß-silicon, and syn-transfer of the proton to give the syn-product, where each step follows a distinct stereochemical course. Examination of the reaction landscape also revealed several additional insights: (a) that, in the initial step, the formation of the anti-oriented zwitterionic intermediate is kinetically more preferable than formation of the syn-oriented zwitterionic intermediate, (b) that intermolecular transfer of a proton is not energetically feasible in non-polar solvents, and (c) that the bulk of the substituents can have a profound effect on the stereochemical course of the reaction. With this detailed understanding, nucleophilic additions to ditetrelenes can be exploited in the future.

The Combination of Cross-Hyperconjugation and σ-Conjugation in 2,5-Oligosilanyl Substituted Siloles.

Reaction of a 2,5-dilithiated silole with excess dichlorodimethylsilane gives the respective 2,5-bis(chlorodimethylsilyl) substituted silole. This compound can be converted to 2,5-bis(oligosilanyl) substituted siloles by addition of a suitable oligosilanide. In the UV spectra of the thus obtained compounds the lowest energy absorptions are bathochromically shifted compared to the absorptions of the two constituents, namely the 2,5-disilyl substituted silole and a trisilane. The bathochromic shift is interpreted as being caused by a mixed σ-conjugation/cross-hyperconjugation. This assumption is supported by TD-DFT calculations, which show a significant contribution from Si-Si bonds to the HOMO of the molecule.

Intramolecular excimer formation in hexakis(pyrenyloxy)cyclotriphosphazene: photophysical properties, crystal structure, and theoretical investigation.

A hexakis(pyrenyloxy)cyclotriphosphazene is synthesized by the reaction of N3P3Cl6 with 2-hydroxypyrene, and its excimer emission through intramolecular interactions in solution and in the solid state has been investigated by fluorescence spectroscopy and X-ray crystallography. Thermal and electrochemical properties were investigated. A DFT benchmark study has been performed to evaluate the intramolecular interactions and molecular orbital levels by comparing with the experimental results.

Quantum chemical modeling of the inhibition mechanism of monoamine oxidase by oxazolidinone and analogous heterocyclic compounds.

Monoamine oxidase (MAO, EC 1.4.3.4) is responsible from the oxidation of a variety of amine neurotransmitters. MAO inhibitors are used for the treatment of depression or Parkinson's disease. They also inhibit the catabolism of dietary amines. According to one hypothesis, inactivation results from the formation of a covalent adduct to a cysteine residue in the enzyme. If the adduct is stable enough, the enzyme is inhibited for a long time. After a while, enzyme can turn to its active form as a result of adduct breakdown by ß-elimination. In this study, the proposed inactivation mechanism was modeled and tested by quantum chemical calculations. Eight heterocyclic methylthioamine derivatives were selected to represent the proposed covalent adducts. Activation energies related to their ß-elimination reactions were calculated using ab initio and density functional theory methods. Calculated activation energies were in good agreement with the relative stabilities of the hypothetical adducts predicted in the literature by enzyme inactivation measurements.

A test of improved force field parameters for urea: molecular-dynamics simulations of urea crystals.

Molecular-dynamics (MD) simulations of urea crystals of different shapes (cubic, rectangular prismatic, and sheet) have been performed using our previously published force field for urea. This force field has been validated by calculating values for the cohesive energy, sublimation temperature, and melting point from the MD data. The cohesive energies computed from simulations of cubic and rectangular prismatic urea crystals in vacuo at 300 K agreed very well with the experimental sublimation enthalpies reported at 298 K. We also found very good agreement between the melting points as observed experimentally and from simulations. Annealing the crystals just below the melting point leads to reconstruction to form crystal faces that are consistent with experimental observations. The simulations reveal a melting mechanism that involves surface (corner/edge) melting well below the melting point, and rotational disordering of the urea molecules in the corner/edge regions of the crystal, which then facilitates the translational motion of these molecules.

Formation of the Vilsmeier-Haack complex: the performance of different levels of theory.

Because of discrepancies in the available experimental data, an extensive theoretical investigation of the formation of the Vilsmeier-Haack (VH) complex has been carried out. The barriers to complex formation calculated using eight different density functional methods (BLYP, B2-PLYP, B3LYP, B3PW91, MPW1K, M06-2X, and PBE1PBE), MP2, and extrapolation techniques (CBS-QB3, G3B3) with several basis sets (6 - 31 + G, 6 - 311++G, 6 - 311 + (3df,2p), aug-cc-pVDZ, and aug-cc-pVTZ) were compared with experimental data. For the overall reaction, MP2/aug-cc-pVDZ and M06-2X/6-31 + G(d,p) perform best compared to the CBS techniques. The results help clarify some open mechanistic questions.

An improved generalized AMBER force field (GAFF) for urea.

We describe an improved force field parameter set for the generalized AMBER force field (GAFF) for urea. Quantum chemical computations were used to obtain geometrical and energetic parameters of urea dimers and larger oligomers using AM1 semiempirical MO theory, density functional theory at the B3LYP/6-31G(d,p) level, MP2 and CCSD ab initio calculations with the 6-311++G(d,p), aug-cc-pVDZ, aug-cc-pVTZ, and aug-cc-pVQZ basis sets, and with the CBS-QB3 and CBS-APNO complete basis set methods. Seven different urea dimer structures were optimized at the MP2/aug-cc-pVDZ level to obtain accurate interaction energies. Atomic partial charges were calculated at the MP2/aug-cc-pVDZ level with the restrained electrostatic potential (RESP) fitting approach. The interaction energies computed with these new RESP charges in the force field are consistent with those obtained from CCSD and MP2 calculations. The linear dimer structure calculated using the force field with modified geometrical parameters and the new RESP charge set agrees well with available experimental data.

QSPR study on the bioconcentration factors of nonionic organic compounds in fish by characteristic root index and semiempirical molecular descriptors.

The characteristic root index (CRI) was modeled together with four semiempirical molecular descriptors, namely-energies of the highest occupied and the lowest unoccupied molecular orbital (E(HOMO) and E(LUMO)), heat of formation (DeltaH(f)), and dipole moment (micro)-to predict the fish bioconcentration factor (BCF) of 122 nonionic organic compounds. The best fit equation found by "forward multiple linear regression" showed that the topology based CRI was the most important parameter. The addition of quantum chemical descriptors made only a slight improvement in the predictive capability of the Quantitative Structure-Property Relationship (QSPR) model. The CRI was followed by E(HOMO). A two-parameter equation with a correlation coefficient of r = 0.921 was obtained for a diverse set of nonionic organic chemicals. Statistical robustness of the developed model was validated by modified jackknife tests where random deletion of a class of compounds and specific deletion of a set of compounds were both performed. The predictive accuracy of the proposed model was compared with the commonly used K(ow) model and recently published studies in which BCF models were developed. Particular emphasis has been made to clearly define the boundaries for the application of the alternative developed model as well as the quality of estimates.