Mechanistic models for the intramolecular hydroxycarbene–formaldehyde conversion and their intermolecular interactions: Theory and chemistry of radicals,mono‐, and dications of hydroxycarbene and related configurations

We have studied with theoretical and mechanistic models the intramolecular 1,2‐hydrogen shift in trans‐hydroxycarbene‐formaldehyde and trans‐methylhydroxycarbene‐acetaldehyde/vinyl alcohol, and the corresponding intermolecular complexation between hydroxycarbene (cis and trans) with formaldehyde. The purpose of our work is making an analysis of the proposed intramolecular hydrogen shifts mainly based on thermodynamic principles and the product selectivity on monochromatic irradiation of trans‐hydroxycarbene in carbon monoxide and molecular hydrogen, and formaldehyde. A geometric visualization of the various intermolecular complexes between hydroxycarbene and formaldehyde, based on ab initio results, is demonstrated and discussed with a concept abstracted from the van't Hoff dynamics for a regular tetrahedron in which the interstitial carbon changes its position from tetrahedral into a trigonal‐bipyramidal configuration. This concept has been also used for interactions via proton transfer, concretized as hydrogen‐bonded complexation in hydroxycarbene‐formaldehyde. With the introduced definitions for various van't Hoff ratio numbers, it was possible to judge the ab initio results of the intermolecular complexes between the hydroxycarbenes and formaldehyde. To make an eye‐opener, we discuss the role of the carbene lone pair in hydroxycarbene extended to the formation of mono‐ and dications demonstrating intermediates or transition states with an exclusive mechanistic behavior. Especially, substituted diaryl methylene dications are of interest for nucleophilic substitution reactions, which occur via an in‐plane tetracoordinate carbon intermediate, showing coherence with the orbital organization of methylene dications. A reaction of this type differs fundamentally from the classical S reaction. © 2012 Wiley Periodicals, Inc.     

The unique chemistry of platina-beta-diketones

This review presents syntheses, structures and the reactivity of platina-beta-diketones [Pt2{(COR)2H}2(mu-Cl)2] (R = alkyl, omega-phenylalkyl), being the first electronically unsaturated (16 ve; ve-valence electrons) and kinetically labile metalla-beta-diketones. They were found to react with amines, yielding platina-beta-diketonates of platina-beta-diketones having Pt(4) zigzag chains analogous to platinum blue complexes. Reactions of platina-beta-diketones with monodentate and bidentate N-, P-, As-, O-, and S-donor ligands are described resulting in the formation of acyl(hydrido)platinum(IV) complexes, acyl(chloro)platinum(II) complexes, platinum complexes having enamine-amide type ligands, and of platinum(II) complexes with cyclic aminocarbene ligands, respectively. These reactions are discussed in terms of oxidative addition and reductive elimination reactions showing that platina-beta-diketones react as hydroxycarbene complexes whose OH groups are intramolecularly hydrogen-bridged to acyl ligands. Furthermore, the synthesis and structures of dinuclear platinum(II) complexes with bridging mu-acyl(hydroxycarbene) ligands are presented.     

Tautomerization in the formation and collision-induced dissociation of alkali metal cation-cytosine complexes

Noncovalent interactions between alkali metal cations and the various low-energy tautomeric forms of cytosine are investigated both experimentally and theoretically. Threshold collision-induced dissociation (CID) of M(+)(cytosine) complexes with Xe is studied using guided ion beam tandem mass spectrometry, where M(+) = Li(+), Na(+), and K(+). In all cases, the only dissociation pathway observed corresponds to endothermic loss of the intact cytosine molecule. The cross-section thresholds are interpreted to yield 0 and 298 K bond dissociation energies (BDEs) for the M(+)(cytosine) complexes after accounting for the effects of multiple ion-neutral collisions, the kinetic and internal energy distributions of the reactants, and dissociation lifetimes. Ab initio calculations are performed at the MP2(full)/6-31G* level of theory to determine the structures of the neutral cytosine tautomers, the M(+)(cytosine) complexes, and the TSs for unimolecular tautomerization. The molecular parameters derived from these structures are employed for the calculation of the unimolecular rates for tautomerization and the thermochemical analysis of the experimental data. Theoretical BDEs of the various M(+)(cytosine) complexes and the energy barriers for the unimolecular tautomerization of these complexes are determined at MP2(full)/6-311+G(2d,2p) level of theory using the MP2(full)/6-31G* optimized geometries. In addition, BDEs for the Li(+)(cytosine) complexes are also determined at the G3 level of theory. Based upon the tautomeric mixture generated upon thermal vaporization of cytosine, calculated M(+)-cytosine BDEs and barriers to tautomerization for the low-energy tautomeric forms of M(+)(cytosine), and measured thresholds for CID of M(+)(cytosine) complexes, we conclude that tautomerization occurs during both complex formation and CID.     

Novel view on the mechanism of water-assisted proton transfer in the DNA bases: bulk water hydration

In the present work, the conventional static ab initio picture of a water-assisted mechanism of the tautomerization of Nucleic Acid Bases (NABs) in an aqueous environment is enhanced by the classical and Car-Parrinello molecular dynamics simulations. The inclusion of the dynamical contribution is vital because the formation and longevity of the NAB-water bridge complexes represent decisive factors for further tautomerization. The results of both molecular dynamic techniques indicate that the longest time when such complexes exist is significantly shorter than the time required for proton transfer suggested by the static ab initio level of theory. New rate constants of tautomerization corrected for the dynamic effect of environment are proposed based on the first principles molecular dynamics data. Those values are used for the evaluation of a water-assisted mechanism that is feasible in such biological systems as E. coli cell.     

Effect of Sr2+ association on the tautomerization processes of uracil and its dithio- and diseleno-derivatives

The structures and relative stabilities of the complexes formed by uracil and its thio- and seleno-derivatives with the Sr(2+) cation, in the gas phase, have been analyzed by means of G96LYP density functional theory (DFT) calculations. The attachment of the Sr(2+) cation to the heteroatom at position 4 is preferred systematically. Although the enolic forms of uracil and its derivatives should not be observed in the gas phase, the corresponding Sr(2+) complexes are the most stable. The enhanced stability of these tautomers is two-fold, on the one hand Sr(2+) interacts with two basic sites simultaneously, and on the other hand an aromatization of the six-membered ring takes place upon Sr(2+) association. Sr(2+) attachment also has a clear catalytic effect in the tautomerization processes involving uracil and its derivatives. This catalytic effect increases when oxygen is replaced by sulfur or selenium. The Sr(2+) binding energy with uracil and its derivatives is bigger than the tautomerization barriers connecting the dioxo forms with the corresponding enolic tautomers. Consequently, when associated with Sr(2+), all tautomers are energetically accessible and should all be observed in the gas phase.     

Gas-Phase Hydration Thermochemistry of Sodiated and Potassiated Nucleic Acid Bases

Hydration reactions of sodiated and potassiated nucleic acid bases (uracil, thymine, cytosine, and adenine) produced by electrospray have been studied in a gas phase using the pulsed ion-beam high-pressure mass spectrometer. The thermochemical properties, ΔH ( o ) ( n ), ΔS ( o ) ( n ), and ΔG ( o ) ( n ), for the hydrated systems were obtained from hydration equilibrium measurement. The structural aspects of the hydrated complexes are discussed in conjunction with available literature data. The correlation between water binding energies in the hydrated complexes and the corresponding metal ion affinities of nucleobases suggests that a significant (if not dominant) amount of the canonical structure of cytosine undergoes tautomerization during electrospray ionization, and the thermochemical values for cationized cytosine probably correspond to a mixture of tautomeric complexes.     

DFT calculations of amine‐imine tautomerism in some pyrimidine derivatives and their 1:1 and 1:2 complexes with water

Amine‐Imine tautomerization in 2‐amino‐pyrimidine (I), 2‐amino‐4,6‐dichloropyrimidine (II), 2‐amino‐4,6‐dimethylpyrimidine (III), and 2‐amino‐4,6‐dimethoxypyrimidine (IV) and their 1:1 and 1:2 H‐bonded complexes with water have been studied using the B3LYP/6‐31++G** method. Optimum molecular geometries, electronic properties, and energetics of these systems have been discussed. © 2011 Wiley Periodicals, Inc. Int J Quantum Chem, 2011     

CH···O interaction lowers hydrogen transfer barrier to keto-enol tautomerization of β-cyclohexanedione: combined infrared spectroscopic and electronic structure calculation study

Molecular association and keto-enol tautomerization of β-cyclohexanedione (β-CHD) have been investigated in argon matrix and also in a thin solid film prepared by depositing pure β-CHD vapor on a cold (8 K) KBr window. Infrared spectra reveal that, in low-pressure vapor and argon matrix, the molecules are exclusively in diketo tautomeric form. The CH···O hydrogen bonded dimers of the diketo tautomer are produced by annealing the matrix at 28 K. No indication is found for keto-enol tautomerization of β-CHD in dimeric complexes in argon matrix within the temperature range of 8-28 K. On the other hand, in thin film of pure diketo tautomer, the conversion initiates only when the film is heated at temperatures above 165 K. The observed threshold appears to be associated with excitation of the intermolecular modes, and the IR spectra recorded at high temperatures display narrowing of vibrational bandwidths, which has been associated with reorientations of the molecules in the film. The nonoccurrence of tautomerization of the matrix isolated dimer is consistent with the barrier predicted by electronic structure calculations at B3LYP/6-311++G** and MP2/6-311++G** levels of theory. The transition state calculation predicts that CH···O interaction has a dramatic effect on lowering of the tautomerization barrier, from more than 60 kcal/mol for the bare molecule to ~35-45 kcal/mol for dimers.     

Thermodynamics and kinetics of intramolecular water assisted proton transfer in Na+ -1-methylcytosine water complexes

High-level ab initio predictions of the tautomerization equilibrium and rate constants of water-assisted proton transfer of 1-methyl-cytosine (MeC) to its MeC* imino tautomeric form in the presence of up to two water molecules (W) and the Na(+) cation were carried out. The calculated energy values were used to obtain the thermodynamic parameters and equilibrium concentration of MeC, its rare tautomer, and their complexes with up to two water molecules and the Na (+) cation. The rate constants for the tautomerization were obtained by using the instanton approach (a quasiclassical method based on the least-action principle). Hydration of MeC by one water molecule leads to an increase of the concentration of the MeC* tautomer in the equilibrium mixture and a decrease of the barrier of the MeC* formation (to 15.6 kcal/mol). If the Na(+) cation is present, the tautomeric form is much less favored, and the tautomerization barrier increases to 25.2 kcal/mol. It was found that MeC monohydrate has both the highest equilibrium (2.9 x 10(-2)) and rate (7.9 x 10(5) s(-1)) constants of tautomerization in comparison to the MeC*NaW and MeC*Na2W complexes containing the Na(+) cation. Moreover, this study also allows one to estimate the concentration of MeC present in the cell during DNA synthesis as the unwanted tautomer, which in forming a mismatched base pair can cause spontaneous point mutations. Kinetic simulations have demonstrated that the low values of equilibrium (10(-14)-10(-13)) and rate constants (10(-17)-10(-16) s(-1)) of tautomerization make contribution of the MeC*Na(+)W and MeC*Na(+)2W complexes to the point mutations in DNA unlikely. In contrast to these Na(+) complexes, MeC*W can reach an equilibrium concentration of 2.9 x 10(-2) within 10(-7) s; thus, it can increase the probability of the point mutations.     

Theoretical studies of proton-transfer reactions of 2-hydroxypyridine--(H2O)n (n = 0-2) in the ground and excited states

The potential energy profiles for proton-transfer reactions of 2-hydroxypyridine and its complexes with water were determined by MP2, CASSCF and MR-CI calculations with the 6-31G** basis set. The tautomerization reaction between 2-hydroxypyridine (2HP) and 2-pyridone (2PY) does not take place at room temperature because of a barrier of approximately 35 kcal/mol for the ground-state pathway. The water-catalyzed enol-keto tautomerization reactions in the ground state proceed easily through the concerted proton transfer, especially for the two-water complex. The S1 tautomerization between the 2HP and 2PY monomers has a barrier of 18.4 kcal/mol, which is reduced to 5.6 kcal/mol for the one-water complex and 6.4 kcal/mol for the two-water complex. The results reported here predict that the photoinduced tautomerization reaction between the enol and keto forms involves a cyclic transition state having one or two water molecules as a bridge.     

Interaction of Ca2+ with uracil and its thio derivatives in the gas phase

The structures and relative stabilities of the complexes formed by uracil and its sulfur derivatives, namely, 2-thio-, 4-thio, and 2,4-dithio-uracil when interacting with Ca(2+) in the gas phase have been analyzed by means of density functional theory (DFT) calculations carried out at the B3LYP/6-311++G(3df,2p)//B3LYP/6-31+G(d,p) level. For uracil and 2,4-dithiouracil, where the two basic sites are the same, Ca(2+) attachment to the heteroatom at position 4 is preferred. However, for the systems where both types of basic centers, a carbonyl or a thiocarbonyl group, are present, Ca(2+)-oxygen association is favored. The most stable complexes correspond to structures with Ca(2+) bridging between the heteroatom at position 2 of the 4-enol (or the 4-enethiol) tautomer and the dehydrogenated ring nitrogen, N3. The enhanced stability of these enolic forms is two-fold, on the one hand Ca(2+) interacts with two basic sites and on the other triggers a significant aromatization of the ring. Besides, Ca(2+) association has a clear catalytic effect on the tautomerization processes which connect the oxo-thione forms with the enol-enethiol tautomers. Hence, although the enol-enethiol tautomers of uracil and its thio derivatives should not be observed in the gas phase, the corresponding Ca(2+) complexes are the most stable species and should be accessible, because the tautomerization barriers are smaller than the Ca(2+) binding energies.     

Facile oxygenation reactions of ruthenium acetylide complex containing substituted olefinic group

Reaction of the ruthenium acetylide complex Cp(dppe)RuC≡CCH(OMe)CPh(2)-CH(2)CH=CMe(2) (5a) with oxygen readily gives acetone and the acyl complex 6 in almost quantitative yield. Protonation of 5a is followed by an elimination of MeOH and a hydroxyl addition at Cα in the presence of water to give the hydroxycarbene complex 7a. The structures of the acyl complex 6 and the hydroxycarbene complex 7c are fully characterized by single crystal X-ray diffraction analysis.     

Mechanistic aspects regarding the formation of metal vinylidenes from alkynes and related reactions

This review focuses on the tautomerization mechanism between alkynes and vinylidene units taking place in the coordination sphere of transition metal fragments. Reactions of vinylidene complexes as well as catalytic reactions involving a metal-vinylidene intermediate are also reviewed from the mechanistic point of view.     

2-巯基苯并咪唑及其类似物互变异构的理论研究

采用B3LYP/6-311G**方法, 计算了2-巯基苯并咪唑及其类似物(2-巯基苯并噁唑、2-巯基苯并噻唑、2-羟基苯并咪唑、2-羟基苯并噁唑、2-羟基苯并噻唑以及2-巯基咪唑、2-巯基噁唑、2-巯基噻唑、2-羟基咪唑、2-羟基噁唑、2-羟基噻唑)的(硫)醇式与(硫)酮式结构进行质子迁移的3种可能途径: (a)分子内质子迁移; (b)水助质子迁移; (c)甲醇助质子迁移．结果表明, 途经b和c所需要的活化能较小, 氢键在降低反应活化能方面起重要作用．采用PCM方法研究了反应体系的溶剂化效应．结果表明孤立分子、一水合物和一甲醇合物的最稳定异构体相同, 都为(硫)酮式, 与气相结论一致．溶剂化效应对异构化能垒的影响较小.     

硫、氮双齿配体与Cd(II)和Hg(II)配合物的合成与表征

以HMFC[(反)-肉桂酰基二茂铁缩(S)-甲基二硫代碳酰腙]与HBFC[(反)-肉桂酰基二茂铁缩(S)-苄基二硫代碳酰腙]两种Schiff碱分别与醋酸镉[Cd(OAc)2?2H2O]、醋酸汞[Hg(OAc)2]反应,合成了6个未见文献报道的配合物Cd(MFC)2?H2O,Cd(MFC)OAc,Cd(BFC)2,Hg(MFC)2,Hg(MFC)OAc,Hg(BFC)2,考察了其物理性质,并利用元素分析、IR,1HNMR及摩尔电导表征了其组成、可能结构,推断了配位过程.结果表明:这两种Schiff碱都是反式双齿配体,经烯硫醇化并失去质子后,以负硫离子与过渡金属离子形成共价键,氮原子与中心金属离子形成配位键.     

Excited-State Double Proton Transfer in 1-Azacarbazole Hydrogen Bonded Complexes

Excited-state double proton transfer (ESDPT) has been studied in a variety of 1-azacarbazole (1AC) hosted hydrogen-bonded complexes. In 1 AC/carboxylic acids hydrogen bonded complexes, large association constants of > 1.0 × 10⁴ M^?1 are measured in the ground state and the rate of ESDPT is » 5.0 × 10⁹ s^?1, resulting in a dominant proton-transfer tautomer emission. In several 1 AC/lactam hydrogen bonded complexes, however, spectral and dynamic results show the existence of a fast excited-state equilibrium between normal and proton-transfer tautomer states. The result can be tentatively rationalized by a non-catalytic ESDPT mechanism incorporating tautomerization energy of the guest molecule.     

Effects of the ionization in the tautomerism of uracil: A reaction electronic flux perspective

The one‐step tautomerization processes of uracil and its radical cation and radical anion have been investigated in the light of the reaction force and reaction electronic flux (REF) formalisms. The relative energies of the different tautomers as well as the corresponding tautomerization barriers have been obtained through the use of the G4 high‐level ab initio method and by means of B3LYP/6‐311+G(3df,2p)//B3LYP/6‐311+G(d, p) calculations. Systematically, the enol radical cations are more stable in relative terms than the neutral, due to the higher ionization energy of the diketo forms with respect to the enolic ones. Conversely, the enol radical anions, with the only exception of the 2‐keto‐N1 anion, are found to be less stable than the neutral. The effects of the ionization are also sizable on the tautomerization barriers although this effect also depends on the particular tautomerization process. The reaction force analysis shows that all reactions are mainly activated through structural rearrangements that initiate the electronic activity. This electronic activity is monitored along the reaction coordinate through the REF that obeys a delicate balance between the acid and basic character of the atoms involved in the hydrogen transfer. © 2015 Wiley Periodicals, Inc.     

Density functional study on the reaction mechanism of proton transfer in 2-pyridone: effect of hydration and self-association

The proton-transfer mechanism in the isolated, mono, dehydrated forms and dimers of 2-pyridone and the effect of hydration or self-assistance on the transition state structures corresponding to proton transfer from the keto form to the enol form have been investigated using B3LYP and BH-LYP hybrid density functional methods at the 6-311++G (2d, 2p) basis set level. The barrier heights for both H2O-assisted and self-assisted reactions are significantly lower than that of the bare tautomerization reaction from 2-pyridone to 2-hydroxypyridine, implying the importance of the superior catalytic effect of H2O and (H2O)2 and the important role of 2-pyridone itself for the intramolecular proton transfer. Long-range solvent effects have also been taken into account by using the continuum model (Onsager model and polarizable continuum model (PCM)) of water. The tautomerization energies and the potential energy barriers are increased both for the water-assisted and for the self-assisted reaction because of the bulk solvent, which imply that the tautomerization of PY becomes less favorable in the polar solvent.     

Ab initio study of gas phase and water-assisted tautomerization of maleimide and formamide

Maleimide serves as an important starting material in the synthesis of drugs and enzyme inhibitors. In the present paper, knowing the importance of tautomerization in maleimide for its drug action, potential energy surface of maleimide is studied and its tautomerization has been discussed and compared with tautomerization of formamide. Gas phase tautomerization of maleimide requires large amount of energy (23·21 kcal/mol) in comparison to formamide (15·05 kcal/mol) at HF/6-31+G* level. Thus making the proton transfer reaction a difficult process in gas phase. Water molecule lowers the energy barrier of tautomerization thus facilitating the tautomerization of maleimide to 5-hydroxy-pyrrol-2-one. Water assisted tautomerization of maleimide requires 19·60 kcal/mol energy at HF/6-31+G* and 17·63 kcal/mol energy at B3LYP/6-31+G* level, a decrease of 3·61 and 5·96 kcal/mol over gas phase tautomerization. Whereas, tautomerization of formamide requires 14·16 and 12·84 kcal/mol energy, a decrease of 0·89 and 2·01 kcal/mol energy over gas phase tautomerization at HF/6-31+G* and B3LYP/6-31+G* level, respectively. Water-assisted tautomerization in maleimide and formamide showed that difference in energy barrier reduces to 2·83 kcal/mol from 10·41 kcal/mol (in gas phase) at B3LYP level, which resulted that maleimide readily undergoes tautomerization in water molecule.     

Theoretical studies of iridium-mediated tautomerization of substituted pyridines

Room temperature reaction of [Ir(COD)₂]BF₄ (COD = 1,5-cyclooctadiene) and amide-tethered or simple 2,3′-bipyridyls gave iridium(I) complexes bearing chelating protic pyridylidenes. This protic pyridylidene tautomer is stabilized by both chelation effect and by hydrogen bonding. The mechanistic details of this tautomerization of N-heterocycles to N-heterocyclic carbenes (NHCs) were investigated using the density functional theory (DFT). DFT studies suggested that cyclometalation of 2,3′-bipyridyls took place to give an iridium(III) hydride, which subsequently undergoes formal 1,3-hydrogen shift from the iridium to the pyridyl nitrogen atom. Two possible mechanisms of this formal 1,3-hydrogen shift process have been examined: the β-insertion of the hydride into an olefin followed by proton abstraction and the water-assisted proton transfer via a cyclic transition state. The latter mechanism is strongly favored in the presence of a catalytic amount of water, and this mechanism is applicable to the tautomerization of both amide-tethered and amide-free 2,3′-bipyridyls.