Thermodynamic parameters ΔΔH and ΔΔS as probes for the transition state in the reaction of N-phenyltriazolinedione with alkenes in nucleophilic solvents

The thermodynamic parameters, ΔΔH^# and ΔΔS^#, were determined for the interception of an intermediate, with the structural characteristics of an aziridinium imide, by nucleophilic solvents during the reaction of 2-methyl-2-butene with N-phenyltriazolinedione. The experimentally measured parameters were found to be in favor of an S_N2-‘like’ transition state and showed strong dependence on the bulkiness of the incoming molecule of the nucleophile-solvent.     

Reaction of a triazolinedione with simple alkenes. Isolation and characterization of hydration products

The reaction of N-phenyltriazolinedione with three simple alkyl-substituted alkenes in water/alcohol or water/acetone solution was found to give a mixture of the corresponding ene and water addition products. The new hydration products were characterized by spectroscopy, and in one case, also by X-ray diffraction analysis. Thermodynamic parameters were determined for the reactions involving 2-methylbut-2-ene, TriME, and 2,3-dimethylbut-2-ene, TetraMe, in accordance with an ‘S_N2-like’, nucleophilic attack on a closed aziridinium imide (AI) intermediate by water.     

Stereoelectronic and solvent effects on the allylic oxyfunctionalization of alkenes with singlet oxygen

The factors that control the stereochemistry of sensitized photooxygenation of alkenes via singlet oxygen (ene reaction) are selectively reported. We also introduce our most recent stereoelectronic effects on the singlet oxygen-ene reaction. The origin of site selectivity and solvent-dependent stereoselectivity in this classical ene reaction with simple as well as functionalized alkenes is highlighted. These studies and other similar studies have enhanced substantially the utility of singlet oxygen in the synthesis of natural and non-natural products.     

The scaled-particle theory and solvent isotope effects on the thermodynamic properties of inert solutes in water and methanol

The scaled-particle theory has been applied to the calculation of the thermodynamic changes associated with the formation of a cavity in several isotopic varieties of liquid water and methanol. From these results, the thermodynamic functions for the transfer of a cavity (or a hard-sphere solute) have been computed for the following solvent pairs: H₂OD₂O, H₂OH₂ ¹⁸O, H₂ ¹⁸OD₂ ¹⁸O, D₂OD₂ ¹⁸O, CH₃OHCH₃OD. For the last two of these solvents, density measurements required for the calculations were carried out as a function of temperature. The calculated deuterium solvent isotope effect on the heats and entropies of hard-sphere solutes in water is much greater than the¹⁸O isotope effect; the former also exhibits a more pronounced temperature dependence. The transfer functions computed for hard-sphere solutes are compared to experimental data on the transfer of various solutes from H₂O to D₂O and from CH₃OH to CH₃OD. In most of the cases examined, the cavity effect accounts for a large part of the transfer quantities measured for rare gases, hydrocarbons, and solutes containing a significant hydrocarbon substituent.     

Volumetric properties of mixtures of water and methanol H/D-isotopomers between 5 and 45°C

Densities of H/D-isotopomers mixtures of water (H₂O, D₂O) and methanol (CH₃OH, CD₃OH, CH₃OD, and CD₃OD) over the full range of compositions were measured at 5, 15, 25, 35, and 45°C. Results have been used to calculate molar volumes, excess molar volumes, apparent molar volumes, and isotope effects of the mixtures. The volumetric properties are discussed in terms of the structural changes in water-methanol solutions under the influence of isotope substitution.     

D2O–H2O solvent isotope effects on the volumetric properties of aqueous 1,3-dimethyl-2-imidazolidinone between (278.15 and 318.15) K

Densities of dilute solutions of 1,3-dimethyl-2-imiazolidinone in H₂O and D₂O, with the solute mole-fractions ranging up to 0.01, have been measured with an error of 1.5 · 10⁻⁵ g · cm⁻³ at (278.15, 288.15, 298.15, 308.15, 313.15, and 318.15) K and atmospheric pressure using a vibrating-tube densimeter. The partial molar volumes of the dissolved DMI (down to the infinite dilution) and solvent (H₂O or D₂O) as well as the excess molar volumes of the isotopically distinguishable solutions have been calculated. The effects of the solvent isotope substitution, solute concentration and temperature on the volume changes caused by DMI hydration have been considered. The obvious relationship between the D₂O–H₂O solvent isotope effects on the partial molar volume and enthalpy of solution of DMI has been discovered.     

Solvent isotope effects on the phase-transition properties of lipid bilayers

Highly sensitive differential scanning microcalorimetry (DSC) has been used to investigate the phase transition properties of lipid vesicles prepared from 1,2-distearoyl-L-3-glyceryl-phosphatidylcholine (DSPC) in H(2)O and D(2)O. The data show that the response of pre-transition properties to D(2)O-->H(2)O substitution is stronger than the main transition properties. We find that there is a small increase in the phase transition temperature (DeltaT approximately 0.5 K) and in the co-operative unit in the main transition. The increase in enthalpy (DeltaH congruent with1 kJ(.)mol(-1)) and in transition temperature (DeltaT congruent with2 K) observed in the pre-transition is comparable with that observed in quite different processes and systems, i.e. melting of nucleic acids and proteins and gel formation. It is suggested that D(2)O-->H(2)O substitution affects the thermal transition in these systems in such a way that the contributions of enthalpy and entropy to structural reorganization of water in these processes is modified.     

Effect of H/D isotope substitution on polarizability of methanol molecules

The electron polarizabilities (α₀·10²⁴/cm³ molec.⁻¹) were estimated from the data on refractive indices and molar volumes of H/D isotopomers of methanol at 25 °C using the Lorentz-Lorentz formula: 3.265 (CH₃OH), 3.260 (CH₃OD), 3.235 (CD₃OH), and 3.231 (CD₃OD). A relationship between the isotope effects for α₀ and volume (packing) changes in the structure of liquid methanol induced by deuterosubstitution in the methanol molecule was proposed. __________ Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1927–1928, August, 2005.     

Solvent isotope effects on the complexation and exchange kinetics of Tl(I), K and Na with 18-crown-6 by competitive NMR spectroscopy: Competition between homo- and heterobimolecular cations exchange

The thermodynamic properties of complexation and exchange kinetics of thallium by 18-crown-6 have been studied by thallium NMR spectroscopy. Effects of solvent isotope, counterion (ClO₄⁻ and NO₃⁻) and presence of competitive cations, such as Na⁺ and K⁺, on the exchange characteristics of the system have been considered. The obvious relationships between the effects of D₂O-H₂O solvent isotope on the thermodynamic properties and activation parameters of complexation have been investigated. In the absence of competitor cations, the mechanism of thallium exchange is unimolecular decomplexation and in the presence of competitor cations, homobimolecular cation exchange is the predominant mechanism at low concentrations of the ligand. At higher concentrations of the ligand, the measured rate constants show that the complexation/decomplexation process obeys a heterobimolecular cation interchange mechanism. The rate constants ratios (k_D2O/k_H2O < 1) for unimolecular mechanisms also show an inverse solvent isotope effect.     

Synthesis of the C(1)-C(16) fragment of bryostatins using an ‘ene’ reaction between an allylsilane and an alkynone

The zinc(II) iodide mediated ‘ene’ reaction between (4R)-4,5-bis-(tert-butyldimethylsilyloxy)-2-(trimethylsilylmethyl)pent-1-ene (43) and (5S,7R,9S)-5,11-dibenzyloxy-4,4-dimethyl-7,9-dihydroxy-7,9-O-isopropylideneundec-1-yn-3-one (53) gave the (E)-vinylsilane 54 with excellent stereoselectivity. Simultaneous deprotection and cyclisation via a stereoselective oxy-Michael reaction gave the bicyclic acetal 57 after treatment with trimethyl orthoformate. A synthesis of the ester 60 corresponding to the C(1)-C(16) fragment of the bryostatins was then completed by O-silylation, oxidative cleavage of the methylene group and a stereoselective condensation of the resulting ketone 59 with the chiral phosphonate 61.     

Energy‐dependent normal and unusually large inverse chlorine kinetic isotope effects of simple chlorohydrocarbons in collision‐induced dissociation by gas chromatography‐electron ionization‐tandem mass spectrometry

Kinetic isotope effects (KIEs) occurring in mass spectrometry (MS) can provide in‐depth insights into the fragmentation behaviors of compounds of interest in MS. Yet, the fundamentals of KIEs in collision‐induced dissociation (CID) in tandem mass spectrometry (MS/MS) are unclear, and information about chlorine KIEs (Cl‐KIEs) of organochlorines in MS is particularly scarce. This study investigated the Cl‐KIEs of dichloromethane, trichloroethylene, and tetrachloroethylene during CID using gas chromatography‐electron ionization triple‐quadrupole MS/MS. Cl‐KIEs were evaluated with MS signal intensities. All the organochlorines presented large inverse Cl‐KIEs (<1, the departures of Cl‐KIEs from 1 denote the magnitudes of Cl‐KIEs), showing the largest magnitudes of 0.797, 0.910, and 0.892 at the highest collision energy (60 eV) for dichloromethane, trichloroethylene, and tetrachloroethylene, respectively. For dichloromethane, both intra‐ion and inter‐ion Cl‐KIEs were studied, within the ranges of 0.820–1.020 and 0.797–1.016, respectively, showing both normal and inverse Cl‐KIEs depending on collision energies. The observed Cl‐KIEs generally declined from large normal to extremely large inverse values with increasing collision energies from 0 to 60 eV but were inferred to be independent of MS signal intensities. The Cl‐KIEs are dominated by critical energies at low internal energies of precursor ions, resulting in normal Cl‐KIEs; while at high internal energies, the Cl‐KIEs are controlled by rotational barriers (or looseness/tightness of transition states), which lead to isotope‐competitive reactions in dechlorination and thereby inverse Cl‐KIEs. It is concluded that the Cl‐KIEs may depend on critical energies, bond strengths, available internal energies, and transition state looseness/tightness. The findings of this study yield new insights into the fundamentals of Cl‐KIEs of organochlorines during CID and may be conducive to elucidating the underlying mechanisms of KIEs in collision‐induced and photo‐induced reactions in the actual world.     

Theoretical study on the substitution and insertion reactions of silylenoid H2SiLiF with CH3XHn−1 (X = F, Cl, Br, O, N; n = 1, 1, 1, 2, 3)

The substitution and insertion reactions of H₂SiLiF (A) with CH₃XH_n−1 (X = F, Cl, Br, O, N; n = 1, 1, 1, 2, 3) have been studied using density functional theory. The results indicate that the substitution reactions of A with CH₃XH_n−1 proceed via two reaction paths, I and II, forming the same product H₂SiFCH₃. The insertion reactions of A with CH₃XH_n−1 form H₂SiXH_n−1CH₃. The following conclusions emerge from this work. (i) The substitution reactions of A with CH₃XH_n−1 occur in a concerted manner. The substitution barriers of A with CH₃XH_n−1 for both pathways decrease with the increase of the atomic number of the element X for the same family systems or for the same row systems. Path I is more favorable than path II. (ii) A inserts into a C-X bond via a concerted manner, and the reaction barriers increase for the same-row element X from right to left in the periodic table, whereas change very little for the systems of the same-family element X. (iii) The substitution reactions occur more readily than the insertion reactions for A with CH₃XH_n−1 systems. (iv) All substitution and insertion reactions of A with CH₃XH_n−1 are exothermic. (v) In solvents, the substitution reaction process of A with CH₃XH_n−1 is similar to that in vacuum. The barrier heights in solvents increase in the order CH₃F < CH₃Cl < CH₃Br < CH₃OH < CH₃NH₂. The solvent polarity has little effects on the substitution barriers. The calculations are in agreement with experiments.     

Deuterium isotope effects observed during competitive binding chiral recognition electrospray ionization--mass spectrometry of cinchona alkaloid-based systems

Deuterium isotope effects are reported for binding between tert-butylcarbamoyl-quinine/quinidine chiral selectors and isotopomeric quasienantiomers of N-(3,5-dinitrobenzoyl)leucine measured using electrospray ionization-mass spectrometry (ESI-MS) and competitive binding. Evaluation of mixtures of each selector with one labeled and one unlabeled enantiomeric selectand of identical configuration showed a significant difference in measured ion abundances of diastereomeric complexes between the selector and each selectand. It was found that in some cases, the complex containing the nondeuterated selectand was 15% more abundant than its deuterated counterpart. On the basis of an assessment of solution- and gas-phase isotope effects reported in the literature, a series of control experiments were performed to study the origin of the effects. On the basis of these measurements, our preliminary conclusion is that the differing gas-phase physicochemical nature of the deuterated versus nondeuterated selectand represents the strongest contribution to the observed effect in this chiral molecular recognition system.     

Ab initio path‐integral calculations of kinetic and equilibrium isotope effects on base‐catalyzed RNA transphosphorylation models

Detailed understandings of the reaction mechanisms of RNA catalysis in various environments can have profound importance for many applications, ranging from the design of new biotechnologies to the unraveling of the evolutionary origin of life. An integral step in the nucleolytic RNA catalysis is self‐cleavage of RNA strands by 2′‐O‐transphosphorylation. Key to elucidating a reaction mechanism is determining the molecular structure and bonding characteristics of transition state. A direct and powerful probe of transition state is measuring isotope effects on biochemical reactions, particularly if we can reproduce isotope effect values from quantum calculations. This article significantly extends the scope of our previous joint experimental and theoretical work in examining isotope effects on enzymatic and nonenzymatic 2′‐O‐transphosphorylation reaction models that mimic reactions catalyzed by RNA enzymes (ribozymes), and protein enzymes such as ribonuclease A (RNase A). Native reactions are studied, as well as reactions with thio substitutions representing chemical modifications often used in experiments to probe mechanism. Here, we report and compare results from eight levels of electronic‐structure calculations for constructing the potential energy surfaces in kinetic and equilibrium isotope effects (KIE and EIE) computations, including a “gold‐standard” coupled‐cluster level of theory [CCSD(T)]. In addition to the widely used Bigeleisen equation for estimating KIE and EIE values, internuclear anharmonicity and quantum tunneling effects were also computed using our recently developed ab initio path‐integral method, that is, automated integration‐free path‐integral method. The results of this work establish an important set of benchmarks that serve to guide calculations of KIE and EIE for RNA catalysis. © 2014 Wiley Periodicals, Inc.     

On the theory of solvent effects

A simple electrostatic analysis is given of the virtual charge (solvaton) model to represent the environment effect on the electronic wave function of a solute immersed in a polarizable surrounding. New features of this model are found. The classical aspects are discussed and secondly the quantal implications are considered. A correct Hartree-Fock-like operator is derived which represents an electron in a molecular orbital subjected to the average effect of the other electrons and to the reaction field produced by the virtual charges on the atomic centers.A general formalism based on the preceding model is presented in appendix. The final equations have a form similar to Newton's equation to represent a solvated electron. Unlike some other theories in this field, there is no cut-off involved in the evaluation of the molecular integrals.