The acidity and proton affinity of the damaged base 1,N6-ethenoadenine in the gas phase versus in solution: intrinsic reactivity and biological implications

1,N(6)-ethenoadenine (epsilonA) is a highly mutagenic lesion that is excised from human DNA by the enzyme alkyladenine DNA glycosylase (AAG). In an effort to understand the intrinsic properties of 1,N(6)-ethenoadenine, we examined its gas phase acidity and proton affinity using quantum mechanical calculations and mass spectrometric experimental methods. We measure two acidities for epsilonA: a more acidic site (DeltaH(acid) = 332 kcal mol(-1); DeltaG(acid) = 325 kcal mol(-1)) and a less acidic site (DeltaH(acid) = 367 kcal mol(-1); DeltaG(acid) = 360 kcal mol(-1)). We also find that the proton affinity of the most basic site of 1,N(6)-ethenoadenine is 232-233 kcal mol(-1) (GB = 224 kcal mol(-1)). These measurements, when compared to calculations, establish that, under our experimental conditions, we have only the canonical tautomer of 1,N(6)-ethenoadenine present. We also compare the gas phase acidic properties of epsilonA with that of the normal bases adenine and guanine and find that epsilonA is the most acidic. This supports the theory that AAG and other related enzymes may cleave damaged bases as anions. Furthermore, comparison of the gas phase and aqueous acidities indicates that the nonpolar environment of the enzyme enhances the acidity differences of epsilonA versus adenine and guanine.     

Acidity of adenine and adenine derivatives and biological implications. A computational and experimental gas-phase study

The gas-phase acidities of adenine, 9-ethyladenine, and 3-methyladenine have been investigated for the first time, using computational and experimental methods to provide an understanding of the intrinsic reactivity of adenine. Adenine is found to have two acidic sites, with the N9 site being 19 kcal mol(-1) more acidic than the N10 site; the bracketed acidities are 333 +/- 2 and 352 +/- 4 kcal mol(-1), respectively. Because measurement of the less acidic site can be problematic, we benchmarked the adenine N10 measurement by bracketing the acidity of 9-ethyladenine, which has the N9 site blocked and allows for exclusive measurement of the N10 site. The acidity of 9-ethyladenine brackets to 352 +/- 4 kcal mol(-1), comparable to that of the N10 site of the parent adenine. Calculations and experiments with 3-methyladenine, a harmful mutagenic nucleobase, uncovered the surprising result that the most commonly written tautomer of 3-methyladenine is not the most stable in the gas phase. We have found that the most stable tautomer is the "N10 tautomer" 10, as opposed to the imine tautomer 3. The bracketed acidity of 10 is 347 +/- 4 kcal mol(-1). Since 10 is not a viable species in DNA, 3 is a likely tautomer; calculations indicate that this form has an extremely high acidity (320-323 kcal mol(-1)). The biological implications of these results, particularly with respect to enzymes that cleave alkylated bases from DNA, are discussed.     

On the unusual stability of valence anions of thymine based on very rare tautomers: A computational study

We characterized anionic states of thymine using various electronic structure methods, with the most accurate results obtained at the CCSD(T)/aug-cc-pVDZ level of theory followed by extrapolations to complete basis set limits. We found that the most stable anion in the gas phase is related to an imino-oxo tautomer, in which the N1H proton is transferred to the C5 atom. This valence anion, aT(c5)(nl), is characterized by an electron vertical detachment energy (VDE) of 1251 meV and it is adiabatically stable with respect to the canonical neutral nT(can) by 2.4 kcal/mol. It is also more stable than the dipole-bound (aT(dbs)(can)), and valence anion aT(val)(can) of the canonical tautomer. The VDE values for aT(dbs)(can)and T(val)(can) are 55 and 457 meV, respectively. Another, anionic, low-lying imino-oxo tautomer with a VDE of 2458 meV has a proton transferred from N3H to C5 aT(c5)(n3). It is less stable than aT(val)(can) by 3.3 kcal/mol. The mechanism of formation of anionic tautomers with the carbons C5 or C6 protonated may involve intermolecular proton transfer or dissociative electron attachment to the canonical neutral tautomer followed by a barrier-free attachment of a hydrogen atom to C5. The six-member ring structure of the anionic tautomers with carbon atoms protonated is unstable upon an excess electron detachment. Within the PCM hydration model, the low-lying valence anions become adiabatically bound with respect to the canonical neutral; becomes the most stable, being followed by aT(c5)(nl), aT(c5)(n3), aT(can), and aT(c5)(nl).     

Stabilization of very rare tautomers of 1-methylcytosine by an excess electron

We characterized valence anionic states of 1-methylcytosine using various electronic structure methods. We found that the most stable valence anion is related to neither the canonical amino-oxo nor a rare imino-oxo tautomer, in which a proton is transferred from the N4 to N3 atom. Instead, it is related to an imino-oxo tautomer, in which the C5 atom is protonated. This anion is characterized by an electron vertical detachment energy (VDE) of 2.12 eV and it is more stable than the anion based on the canonical tautomer by 1.0 kcal/mol. The latter is characterized by a VDE of 0.31 eV. Another unusual low-lying imino-oxo tautomer with a VDE of 3.60 eV has the C6 atom protonated and is 3.6 kcal/mol less stable than the anion of the canonical tautomer. All these anionic states are adiabatically unbound with respect to the canonical amino-oxo neutral, with the instability of 5.8 kcal/mol for the most stable valence anion. The mechanism of formation of anionic tautomers with carbon atoms protonated may involve intermolecular proton transfer or dissociative electron attachment to the canonical neutral tautomer followed by a barrier-free attachment of a hydrogen atom to the C5 or C6 atom. The six-member ring structure of anionic tautomers with carbon atoms protonated is unstable upon an excess electron detachment. Indeed the neutral systems collapse without a barrier to a linear or a bicyclo structure, which might be viewed as lesions to DNA or RNA. Within the PCM hydration model, the anions become adiabatically bound with respect to the corresponding neutrals, and the two most stable tautomers have a carbon atom protonated.     

Gas-phase acidity studies of multiple sites of adenine and adenine derivatives

The acidities of multiple sites in the purine nucleobase adenine (1) and adenine alkyl derivatives 9-ethyladenine (2), 3-methyladenine (3), 1-methyladenine (4), and N,N-dimethyladenine (5) have been investigated for the first time, using computational and experimental methods to provide an understanding of adenine reactivity. We have previously measured two acidic sites on adenine, with the N9 site being 19 kcal mol(-)(1) more acidic than the N10 site (333 +/- 2 versus 352 +/- 4 kcal mol(-)(1), respectively). In this work, we have established that 9-ethyladenine has two sites more acidic than water: the N10 (352 +/- 4 kcal mol(-)(1)) and the C8 (374 +/- 2 kcal mol(-)(1)). We have likewise measured two acidities for 3-methyladenine, the N10 (347 +/- 4 kcal mol(-)(1)) and the C2 (370 +/- 3 kcal mol(-)(1)). For 1-methyladenine and N,N-dimethyladenine, we measure the N9H acidity to be 331 +/- 2 and 333 +/- 2 kcal mol(-)(1), respectively. We believe that the bracketing of only one site for the latter species is a kinetic effect, which we discuss further in the paper. Computationally, we have found the interesting result that some of the vinylic C-H sites in these purine bases are predicted to be much more acidic than water (DeltaH(acid) = 390.7 kcal mol(-)(1)) in the gas phase, on the order of 373 kcal mol(-)(1). The acidic vinylic C-H sites are always adjacent to an N-R group, and this pattern is maintained regardless of whether the site is on the five- or six-membered ring of the purine. Vinylic C-H sites elsewhere on the purine have calculated acidities of about 400 kcal mol(-)(1). The differing acidities are interpreted through electrostatic potential calculations. We also relate our results to the intriguing biochemical decarboxylation of orotate ribose monophosphate, which involves a vinylic anion adjacent to an N-R group; this decarboxylation is the last step in the de novo biosynthesis of pyrimidine nucleotides, and the enzyme that catalyzes the reaction, orotate ribose monophosphate decarboxylase, has been the subject of intense study recently, as its mechanism remains elusive.     

Gas-phase acid-base properties of melamine and cyanuric acid

The thermochemical properties of melamine and cyanuric acid were characterized using mass spectrometry measurements along with computational studies. A triple-quadrupole mass spectrometer was employed with the application of the extended Cooks kinetic method. The proton affinity (PA), gas-phase basicity (GB), and protonation entropy (Δ_pS) of melamine were determined to be 226.2 ± 2.0 kcal/mol, 218.4 ± 2.0 kcal/mol, and 26.2 ± 2.0 cal/mol K, respectively. The deprotonation enthalpy (Δ_acidH), gas-phase acidity (Δ_acidG), and deprotonation entropy (Δ_acidS) of cyanuric acid were determined to be 330.7 ± 2.0 kcal/mol, 322.9 ± 2.0 kcal/mol, and 26.1 ± 2.0 cal/mol K, respectively. The geometries and energetics of melamine, cyanuric acid, and related ionic species were calculated at the B3LYP/6-31+G(d) level of theory. The computationally predicted proton affinity of melamine (225.9 kcal/mol) and gas-phase deprotonation enthalpy of cyanuric acid (328.4 kcal/mol) agree well with the experimental results. Melamine is best represented as the imide-like triazine-triamine form and the triazine nitrogen is more basic than the amino group nitrogen. Cyanuric acid is best represented as the keto-like tautomer and the N-H group is the most probable proton donor.     

Optimum geometries and relative energies for cytosine,thymine, uracil,the imino tautomer of cytosine,the enol tautomer of thymine,and the enol tautomer of uracil by the MINDO/2 SCF MO method

A MINDO /2 SCF MO geometry optimization of cytosine (C), thymine (T), uracil (U), the imino tautomer of cytosine (C*), the enol tautomer of thymine (T*), and the enol tautomer of uracil (U*)was made. The optimized geometries for cytosine, thymine, and uracil agree well with crystallographic data. The optimized geometries for the tautomers show the correct trends in bond lengthening and bond angle except for the C4—O4 length and C4—O4—H angle of T* and U*. The energies of tautomerization were found to be 10.3, ?9.0, and ?14.2 kcal/mol for C?C*, T?T*, and U?U*, respectively, when optimized geometries are used. The overestimation of the C4—O4—H angle is speculated to arise because of an inadequacy in the parametrization of the one-center integrals in MINDO /2.     

Polar group enhanced gas-phase acidities of carboxylic acids: an investigation of intramolecular electrostatic interaction

We studied the effects of polar groups on the gas-phase acidities of carboxylic acids experimentally and computationally. In this connection, the gas-phase acidities (DeltaH(acid), the enthalpy of deprotonation, and DeltaG(acid), the deprotonation free energy) of borane-complexed methylaminoacetic acid ((CH(3))2N(BH(3))CH(2)CO(2)H) and methylthioacetic acid (CH(3)S(BH(3))CH(2)CO(2)H) were measured using the kinetic method in a flowing afterglow-triple quadrupole mass spectrometer. The values of DeltaH(acid) and DeltaG(acid) of (CH(3))2N(BH(3))CH(2)CO(2)H were determined to be 328.8 +/- 1.9 and 322.1 +/- 1.9 kcal/mol, and those of CH(3)S(BH(3))CH(2)CO(2)H were determined to be 325.8 +/- 1.9 and 319.2 +/- 1.9 kcal/mol, respectively. The theoretical enthalpies of deprotonation of (CH(3))2N(BH(3))CH(2)CO(2)H (329.2 kcal/mol) and CH(3)S(BH(3))CH(2)CO(2)H (325.5 kcal/mol) were calculated at the B3LYP/6-31+G(d) level of theory. The calculated enthalpies of deprotonation of N-oxide-acetic acid (CH(3)NOCH(2)CO(2)H, 329.4 kcal/mol) and S-oxide-acetic acid (CH(3)SOCH(2)CO(2)H, 328.6 kcal/mol) are comparable to the experimental results for borane-complexed methylamino- and methylthioacetic acids. The enthalpy of deprotonation of sulfone-acetic acid (CH(3)SO2CH(2)CO(2)H, 326.1 kcal/mol) is about 2 kcal/mol lower than the S-oxide-acetic acid. The calculated enthalpy of deprotonation of sulfoniumacetic acid, (CH(3))2S+CH(2)CO(2)H, is 243.0 kcal/mol. Compared to the corresponding reference molecules, CH(3)NHCH(2)CO(2)H and CH(3)SCH(2)CO(2)H, the dipolar group and the monopolar group substituted carboxylic acids are stronger acids by 11-14 and 97 kcal/mol, respectively. We correlated the changes of the acidity upon a polar group substitution to the electrostatic free energy within the carboxylate anion. The acidity enhancements in polar group substituted carboxylic acids are the results of the favorable electrostatic interactions between the polar group and the developing charge at the carboxyl group.     

Na+, Mg2+, and Zn2+ binding to all tautomers of adenine, cytosine, and thymine and the eight most stable keto/enol tautomers of guanine: a correlated ab initio quantum chemical study

Interactions of adenine, cytosine, guanine, and thymine with Na(+), Mg(2+), and Zn(2+) cations were studied using an approximate resolution of identity correlated second-order MP2 (RI-MP2) method with the TZVPP ([5s3p2d1f/3s2p1d]) basis set. All existing tautomers of adenine, cytosine, and thymine and the eight most stable keto/enol tautomers of guanine were considered. Cations bind mostly in a bidentate manner, and stabilization energies of these complexes are larger than those in the case when cations bind in a unidentate manner. The cation...Y (Y equal to N or O) distances for divalent metals are shorter than those for Na(+) and for Zn(2+) are mostly shorter than the Mg(2+)...Y distance. The intermolecular distances between the cation and the base for complexes containing adenine and cytosine are systematically shorter than those for complexes containing guanine and thymine. Only for cytosine the canonical keto/amino tautomer structure with ions represents the global minimum. For guanine, the metalated canonical form is again the most stable, but its stabilization energy is within less than 5% of the stabilization energies of the two other rare tautomers, which indicates that the canonical form and these two rare tautomers could coexist. The canonical structures of adenine and thymine in the presence of ions are considerably less stable (by more than 10%) than the complexes of the rare tautomers. It can be concluded that the interaction of Na(+), Mg(2+), and Zn(2+) cations with cytosine in the gas phase will not induce the change of the canonical form to the rare tautomeric form. In the case of isolated guanine, the equilibrium of the canonical form with rare tautomers can be found. For isolated adenine and thymine the presence of rare tautomers is highly probable.     

Proton transfer to nickel-thiolate complexes. 1. Protonation of [Ni(SC(6)H(4)R-4)(2)(Ph(2)PCH(2)CH(2)PPh(2))] (R = Me, MeO, H, Cl, or NO(2))

The kinetics of the equilibrium reaction between [Ni(SC(6)H(4)R-4)(2)(dppe)] (R= MeO, Me, H, Cl, or NO(2); dppe = Ph(2)PCH(2)CH(2)PPh(2)) and mixtures of [lutH](+) and lut (lut = 2,6-dimethylpyridine) in MeCN to form [Ni(SHC(6)H(4)R-4)(SC(6)H(4)R-4)(dppe)](+) have been studied using stopped-flow spectrophotometry. The kinetics for the reactions with R = MeO, Me, H, or Cl are consistent with a single-step equilibrium reaction. Investigation of the temperature dependence of the reactions shows that DeltaG = 13.6 +/- 0.3 kcal mol(-)(1) for all the derivatives but the values of DeltaH and DeltaS vary with R (R = MeO, DeltaH() = 8.5 kcal mol(-)(1), DeltaS = -16 cal K(-)(1) mol(-)(1); R = Me, DeltaH() = 10.8 kcal mol(-)(1), DeltaS = -9.5 cal K(-)(1) mol(-)(1); R = Cl, DeltaH = 23.7 kcal mol(-)(1), DeltaS = +33 cal K(-)(1) mol(-)(1)). With [Ni(SC(6)H(4)NO(2)-4)(2)(dppe)] a more complicated rate law is observed consistent with a mechanism in which initial hydrogen-bonding of [lutH](+) to the complex precedes intramolecular proton transfer. It seems likely that all the derivatives operate by this mechanism, but only with R = NO(2) (the most electron-withdrawing substituent) does the intramolecular proton transfer step become sufficiently slow to result in the change in kinetics. Studies with [lutD](+) show that the rates of proton transfer to [Ni(SC(6)H(4)R-4)(2)(dppe)] (R = Me or Cl) are associated with negligible kinetic isotope effect. The possible reasons for this are discussed. The rates of proton transfer to [Ni(SC(6)H(4)R-4)(2)(dppe)] vary with the 4-R-substituent, and the Hammett plot is markedly nonlinear. This unusual behavior is attributable to the electronic influence of R which affects the electron density at the sulfur.     

An experimental and computational study of the enantioselective lithiation of N-Boc-pyrrolidine using sparteine-like chiral diamines

The enantioselective lithiation of N-Boc-pyrrolidine using sec-butyllithium and isopropyllithium in the presence of sparteine-like diamines has been studied experimentally and computationally at various theoretical levels through to B3P86/6-31G*. Of the (-)-cytisine-derived diamines (N-Me, N-Et, N-(n)Bu, N-CH(2)(t)Bu, N-(i)Pr) studied experimentally, the highest enantioselectivity (er 95:5) was observed with the least sterically hindered N-Me-substituted diamine, leading to preferential removal of the pro-R proton i.e., opposite enantioselectivity to (-)-sparteine. The experimental result with the N-Me-substituted diamine correlated well with the computational results: at the B3P86/6-31G* level, the sense of induction was correctly predicted; the lowest energy complex of isopropyllithium/diamine/N-Boc-pyrrolidine also had the lowest activation energy (DeltaH++ = 11.1 kcal/mol, DeltaG++= 11.5 kcal/mol) for proton transfer. The computational results with the N-(i)Pr-substituted diamine identified a transition state for proton transfer with activation energies of DeltaH++= 11.7 kcal/mol and DeltaG++= 11.8 kcal/mol (at the B3P86/6-31G* level). Although comparable to (-)-sparteine and the N-Me-substituted diamine, these DeltaH++ and DeltaG++ values are at odds with the experimental observation that use of the N-(i)Pr-substituted diamine gave no product. It is suggested that steric crowding inhibits formation of the prelithiation complex rather than increasing the activation enthalpy for proton transfer in the transition state. Three other ligands (N-H and O-substituted as well as a five-membered ring analogue) were studied solely using computational methods, and the results predict that the observed enantioselectivity would be modest at best.     

Solvation free energies of molecules. The most stable anionic tautomers of uracil

Anionic states of nucleic acid bases are suspected to play a role in the radiation damage processes of DNA. Our recent studies suggested that the excess electron attachment to the nucleic acid bases can stabilize some rare tautomers, i.e. imine-enamine tautomers and other tautomers with a proton being transferred from nitrogen sites to carbon sites (with respect to the canonical tautomer). So far, these new anionic tautomers have been characterized by the gas-phase electronic structure calculations and photoelectron spectroscopy experiments. In the current contribution we explore the effect of water solvation on the stability of the new anionic tautomers of uracil. The accurate free energies of solvation are calculated in a two step approach. The major contribution was calculated using the classical free-energy perturbation adiabatic-charging approach, where it is assumed that the solvated molecule has the charge distribution given by the polarizable continuum model. In the second step the free energy of solvation is refined by taking into account the real, average solvent charge distribution. This is done using our accelerated QM/MM simulations, where the QM energy of the solute is calculated in the mean potential averaged over many MD steps. We found that in water solution three of the recently identified anionic tautomers are 6.5-3.6 kcal mol(-1) more stable than the anion of the canonical tautomer.     

An unusual exchange between alkylidyne alkyl and bis(alkylidene) tungsten complexes promoted by phosphine coordination: kinetic, thermodynamic, and theoretical studies

d0 Tungsten alkylidyne alkyl complex (Me3SiCH2)3W(CSiMe3)(PMe3) (4a) was found to undergo a rare, PMe3-promoted exchange with its bis(alkylidene) tautomer (Me3SiCH2)2W(=CHSiMe3)2(PMe3) (4b). Thermodynamic studies of the exchange showed that 4b is favored and gave Keq and the enthalpy and entropy of the equilibrium: DeltaH degrees = -1.8(0.5) kcal/mol and DeltaS degrees = -1.5(1.7) eu. Kinetic studies of the alpha-H migration between 4a and 4b by variable-temperature NMR gave rate constants k1 and k-1 for the reversible reactions and activation enthalpies and entropies: DeltaH1 = 16.2(1.2) kcal/mol and DeltaS1 = -22.3(4.0) eu for the forward reaction (4a --> 4b); DeltaH2 = 18.0(1.3) kcal/mol and DeltaS2 = -20.9(4.3) eu for the reverse reaction (4b --> 4a). Ab initio calculations at the B3LYP level revealed that PMe3 binds with the bis(alkylidene) tautomer relatively more strongly than with the alkylidyne tautomer and thus stabilizes the bis(alkylidene) tautomer.     

Gas-phase theoretical prediction of the metal affinity of copper(I) ion for DNA and RNA bases

The most stable tautomeric forms of free DNA and RNA bases were considered as substrates for the interaction of Cu(+) ion. Several suitable attachment sites were selected that involved mono- and bi-coordination of the cation. B3LYP/6-311 + G(2df,2p) bond energies showed that copper ion has the major affinity for guanine and cytosine bases. The proposed values of Cu(+) ion affinity are 59.9, 60.0, 80.2, 88.0 and 69.0 kcal mol(-1) for uracil, thymine, cytosine, guanine and adenine, respectively. The preference for the mono- or bi-coordination depends on the particular tautomer for each base.     

Experimental determination of the alpha and beta C--H bond dissociation energies in naphthalene

The acidities of the two different sites in naphthalene (1alpha and 1beta) and the electron affinities of the alpha- and beta-naphthyl radicals were measured using a Fourier transform mass spectrometer. Both carbon-hydrogen bond dissociation energies for naphthalene also were obtained, in this case via the application of a thermodynamic cycle. The final results are DeltaH(o)acid (1alpha) = 394.2+/-1.2 kcal mol(-1), DeltaH(o)acid (1beta) = 395.5+/-1.3 kcal mol(-1), EA(alpha) = 31.6+/-0.5 kcal mol(-1), EA(beta) = 31.6+/-0.5 kcal mol(-1), BDE(1alpha) = 112.2+/-1.3 kcal mol(-1) and BDE(1alpha) = 111.9+/-1.4 kcal mol(-1), and they are compared to benzene and phenyl radical as well as ab initio and density functional theory (B3LYP) calculations.     

Thermodynamics of Inter- and Intramolecular Hydrogen Bonding in (Diphosphine)platinum(II) Diolate Complexes and Its Role in Carbohydrate Complexation Regioselectivity

Thermodynamic data are reported for intermolecular hydrogen-bonding association of 1 and 2 equiv of phenol with [1,3-bis(diphenylphosphino)propane](phenylethane-1,2-diolato)platinum(II) ((dppp)Pt(Ped)) in dichloromethane solution: = -7.0 +/- 0.1 kcal/mol, = -7.7 +/- 0.4 kcal/mol, = -11.3 +/- 0.4 eu, and = -17.8 +/- 1.2 eu. For comparison, the thermodynamics for hydrogen bonding of phenol to triphenylphosphine oxide in dichloromethane were also determined: DeltaH degrees = -5.1 +/- 0.3 kcal/mol; DeltaS degrees = -8.8 +/- 1.0 eu. Competitive coordination exchange reactions have been used to determine the apparent intramolecular hydrogen bond strengths in (dppp)Pt(1,2-O,O'-glycerolate) and (dppp)Pt(1,2-O,O'-butane-1,2,4-triolate) in both dichloromethane (DeltaG(313) = -2.05 +/- 0.05 and -2.52 +/- 0.06 kcal/mol, respectively) and pyridine (DeltaG(313) = -0.62 +/- 0.03 and -0.82 +/- 0.03 kcal/mol, respectively). Based on these findings, the role of hydrogen-bonding interactions in determining the regioselectivities of complexation of carbohydrates to diphosphine Pt(II) is discussed.     

Structure and bonding of Ag(I)-DNA base complexes and Ag(I)-adenine-cytosine mispairs: an ab initio study

High level ab initio calculations have been carried out to characterize the structure, bonding and energetics of Ag(I)-DNA base complexes, including adenine or cytosine, as well as Ag(I)-adenine-cytosine mispairs. The interactions of the Ag cation in all binding sites of all adenine and cytosine tautomers have been considered. The calculations show that in gas phase the canonical form of cytosine is stabilized upon metalation, whereas the lowest energy structure of Ag-adenine correspond to a rare tautomer. Interestingly, the theoretical inspection of metalated adenine-cytosine mispair reveals that the most stable structures are formed from the canonical cytosine and adenine tautomers. The lowest energy structure is planar with adenine and cytosine hydrogen-bonded. Within few kcal/mol nonplanar, conformationally very flexible structures are found, in which the Ag(I) crosslinks an endocyclic nitrogen of adenine and the oxygen of cytosine. Metalated reverse-Wobble type of structures, on the contrary, are predicted much higher in energy.     

Molecular energetics of cytosine revisited: a joint computational and experimental study

A static bomb calorimeter has been used to measure the standard molar energy of combustion, in oxygen, at T = 298.15 K, of a commercial sample of cytosine. From this energy, the standard (p degrees = 0.1 MPa) molar enthalpy of formation in the crystalline state was derived as -(221.9 +/- 1.7) kJ.mol(-1). This value confirms one experimental value already published in the literature but differs from another literature value by 13.5 kJ.mol(-1). Using the present standard molar enthalpy of formation in the condensed phase and the enthalpy of sublimation due to Burkinshaw and Mortimer [J. Chem. Soc., Dalton Trans. 1984, 75], (155.0 +/- 3.0) kJ.mol(-1), results in a value for the gas-phase standard molar enthalpy of formation for cytosine of -66.9 kJ.mol(-1). A similar value, -65.1 kJ.mol(-1), has been estimated after G3MP2B3 calculations combined with the reaction of atomization on three different tautomers of cytosine. In agreement with experimental evidence, the hydroxy-amino tautomer is the most stable form of cytosine in the gas phase. The enthalpies of formation of the other two tautomers were also estimated as -60.7 kJ.mol(-1) and -57.2 kJ.mol(-1) for the oxo-amino and oxo-imino tautomers, respectively. The same composite approach was also used to compute other thermochemical data, which is difficult to be measured experimentally, such as C-H, N-H, and O-H bond dissociation enthalpies, gas-phase acidities, and ionization enthalpies.     

Determination of the electron affinities of alpha- and beta-naphthyl radicals using the kinetic method with full entropy analysis. The C-H bond dissociation energies of naphthalene.

The C - H bond dissociation energies for naphthalene were determined using a negative ion thermochemical cycle involving the gas-phase acidity (Delta H (acid)) and electron affinity (EA) for both the alpha- and beta-positions. The gas-phase acidity of the naphthalene alpha- and beta-positions and the EAs of the alpha- and beta-naphthyl radicals were measured in the gas phase in a flowing after glow-triple quadrupole apparatus. A variation of the Cooks kinetic method was used to measure the EAs of the naphthyl radicals by collision-induced dissociation of the corresponding alpha- and beta-naphthylsulfinate adducts formed by reactions in the flow tube portion of the instrument. Calibration references included both pi and sigma radicals, and full entropy analysis was performed over a series of calibration curves measured at collision energies ranging from 3.5 to 8 eV (center-of-mass). The measured EAs are 33.0 +/- 1.4 and 31.4 +/- 1.0 kcal mol(-1) (1 kcal = 4.184 kJ) for the alpha- and beta-naphthyl radicals, respectively. The gas-phase acidities for naphthalene were measured by the DePuy silane cleavage method, which utilizes the relative abundances of aryldimethylsiloxides and trimethylsiloxide that result from competitive cleavages from a proposed penta coordinate hydroxysiliconate intermediate. The measured acidities are 394.0 +/- 5.0 and 397.6 +/- 4.8 kcal mol(-1) for the alpha- and beta- positions, respectively. The C - H bond dissociation energies calculated from the thermochemical cycle are 113.4 +/- 5.2 and 115.4 +/- 4.9 kcal mol(-1) for the alpha- and beta-positions, respectively. These energies are, to within experimental error, indistinguishable and are approximately the same as the first bond dissociation energy for benzene.     

Lifting of the degeneracy in semibullvalenes by remote and direct substituents: a quantitative study using variable-temperature carbon-13 NMR spectroscopy

A series of six 1,5-(ethylmethyl)semibullvalenes (1a <==> 1a', 2 <==> 2', 3 <==>3') and two 4(2)-substituted semibullvalenes (4 <==> 4'), each undergoing Cope equilibria between nondegenerate valence tautomers, was investigated by carbon-13 NMR spectroscopy at a range of temperatures in several different solvents. Gompper's treatment of substituent perturbation was extended, specifically accounting for the effects of the substituents on chemical shifts, to allow the determination of the thermodynamic parameters for these skewed equilibria. These new treatments were used to determine the population difference (f - f ') between the valence tautomers and the perturbation thermodynamic quantities DeltaH(P), DeltaS(P), and DeltaG(P). The slow-exchange limit was reached for the parent 1,5-(ethylmethyl)semibullvalenes 3a <==> 3a' from which it was established that the preferred valence tautomer is 3a with the ethyl group on the cyclopropane ring. Despite considerable effort, the slow-exchange limit could not be reached in any of our other remotely substituted semibullvalenes. Provided that the ethyl group always prefers the cyclopropyl position as in 3a, the 1-ethyl-5-methylsemibullvalenes 1a, 2, and 3 are more stable by DeltaH(P) = 0.7-1.7 kJ mol(-1) than their valence tautomers 1a', 2', and 3'. In the directly substituted semibullvalenes (4 left harpoon ovet right harpoon 4'), the preferred valence tautomers 4a and 4b have the bromine atom or the nitrile group on the vinyl position (C(4)) rather than on the cyclopropane ring (C(2)) and are more stable than 4a' and 4b' by DeltaH(P) = 4.8 and 7.0 kJ mol(-1), respectively.