The sodium ion affinities of simple Di-, Tri-, and tetrapeptides

The sodium ion affinities (binding energies) of nineteen peptides containing 2-4 residues have been determined by experimental and computational approaches. Na(+)-bound heterodimers with amino acid and peptide ligands (Pep(1), Pep(2)) were produced by electrospray ionization. The dissociations of these Pep(1)-Na(+)-Pep(2) ions to Pep(1)-Na(+) and Pep(2)-Na(+) were examined by collisionally activated dissociation to construct a ladder of relative affinities via the kinetic method. The accuracy of this ladder was subsequently ascertained by experiments using several excitation energies for four peptide pairs. The relative scale was converted to absolute affinities by anchoring the relative values to the known Na(+) affinity of GlyGly. The Na(+) affinities of AlaAla, HisGly, GlyHis, GlyGlyGly, AlaAlaAla, GlyGlyGlyGly, and AlaAlaAlaAla were also calculated at the MP2(full)/6-311 + G(2d,2p) level of ab initio theory using geometries that were optimized at the MP2(full)/6-31G(d) level for AlaAla or HF/6-31G(d) level for the other peptides; the resulting values agree well with experimental Na(+) affinities. Increasing the peptide size is found to dramatically augment the Na(+) binding energy. The calculations show that in nearly all cases, all available carbonyl oxygens are sodium binding sites in the most stable structures. Whenever side chains are available, as in HisGly and GlyHis, specific additional binding sites are provided to the cation. Oligoglycines and oligoalanines have similar binding modes for the di- and tripeptides, but differ significantly for the tetrapeptides: while the lowest energy structure of GlyGlyGlyGly-Na(+) has the peptide folded around the ion with all four carbonyl oxygens in close contact with Na(+), that of AlaAlaAlaAla-Na(+) involves a pseudo-cyclic peptide in which the C and N termini interact via hydrogen bonding, while Na(+) sits on top of the oxygens of three nearly parallel C=O bonds.     

Experimental validation of theoretical potassium and sodium cation affinities of amides by mass spectrometric kinetic method measurements

In this study the theoretical Gaussian-2 K(+)/Na(+) binding affinities (enthalpies) at 0 K (in kJ mol(-1)) for six amides in the order: formamide (109.2/138.5) < N-methylformamide (117.7/148.6) < acetamide (118.7/149.5) < N,N-dimethylformamide (123.9/156.4) < N-methylacetamide (125.6/157.7) < N,N-dimethylacetamide (129.2/162.6), reported previously (Siu et al., J. Chem. Phys. 2001; 114: 7045-7051), were validated experimentally by mass spectrometric kinetic method measurements. By monitoring the collision-induced dissociation (CID) of K(+)/Na(+)-bound heterodimers of the amides, the relative affinities were shown to be accurate to within +/-2 kJ mol(-1). With these six theoretical K(+)/Na(+) binding affinities as reference values, the absolute K(+)/Na(+) affinities of imidazole, 1-methylimidazole, pyridazine and 1,2-dimethoxyethane were determined by the extended kinetic method, and found to be consistent (to within +/-9 kJ mol(-1)) with literature experimental values obtained by threshold-CID, equilibrium high-pressure mass spectrometry, and Fourier transform ion cyclotron resonance/ligand-exchange equilibrium methods. A self-consistent resolution is proposed for the inconsistencies in the relative order of K(+)/Na(+) affinities of amides reported in the literature. These two sets of validated K(+) and Na(+) affinity values are useful as reference values in kinetic method measurements of K(+)/Na(+) affinity of model biological ligands, such as the K(+) affinities of aliphatic amino acids.     

Absolute proton affinity for acetaldehyde

Dissociative photoionization mass spectrometry has been used to measure appearance energies for the 1-hydroxyethyl cation (CH(3)CH=OH(+)) formed from ethanol and 2-propanol. Molecular orbital calculations for these two unimolecular fragmentation reactions suggest that only methyl loss from ionized 2-propanol does not involve excess energy at the threshold. The experimental appearance energy of 10.31 +/- 0.01 eV for this latter process results in a 298 K heat of formation of 593.1 +/- 1.2 kJ mol(-1) for CH(3)CH=OH(+) and a corresponding absolute proton affinity for acetaldehyde of 770.9 +/- 1.3 kJ mol(-1). This value is supported by both high-level ab initio calculations and a proposed upward revision of the absolute isobutene proton affinity to 803.3 +/- 0.9 kJ mol(-1). A 298 K heat of formation of 52.2 +/- 1.9 kJ mol(-1) is derived for the tert-butyl radical.     

Kinetics and activation parameter analysis for the prebiotic oligocytidylate formation on Na(+)-montmorillonite at 0-100 degrees C

The kinetic analysis of the temperature dependence of the formation of oligocytidylate (oligo(C)) from the 5'-monophosphorimidazolide moiety of cytidine (ImpC) in the presence of Na (+)-montmorillonite (Na (+)-Mont) catalyst has been carried out at 0-100 degrees C. The rate constants for the formation of oligo(C), hydrolysis of ImpC with and without Na (+)-Mont and degradation of oligo(C) were determined. The apparent activation parameters were 30.8 +/- 3.9 kJ mol (-1) ( Ea), 28.3 +/- 4.0 kJ mol (-1) (Delta H++), and -231 +/- 13 J mol (-1) K (-1) (Delta S++) for the formation of the 2-mer; 45.6 +/- 2.9 kJ mol (-1) ( Ea), 43.0 +/- 3.0 kJ mol (-1) (Delta H++), -164 +/- 10 J mol (-1) K (-1) (Delta S++) for the 3-mer; and 45.2 +/- 0.6 kJ mol (-1) ( Ea), 42.7 +/- 0.7 kJ mol (-1) (Delta H++), -159 +/- 2 J mol (-1) K (-1) (Delta S++) for the 4-mer in the presence of Na (+)-Mont. An increasing trend for the rate constants for the formation of oligo(C) in the order 2-mer < 3-mer <4-mer was observed at high temperatures, which is consistent with that observed at low temperatures. These analyses implied for the first time that the associate formation between an activated nucleotide monomer and an elongating oligonucleotide prior to the phosphodiester bond formation during the elongation of an oligonucleotide on a clay surface would be based on the interaction between the two reactants at the phosphoester and/or ribose moieties rather than at the nucleotide bases. The hydrolysis rate of ImpC at 25-100 degrees C was 5.3-10.6 times greater in the presence of Na (+)-Mont than in its absence. Although the degradation of oligo(C) in the presence of Na (+)-Mont was slower than the formation of the 3-mer and longer oligo(C) on Na (+)-Mont, its yield decreased with temperature. This is mainly because the ratios of the rate constant of the 2-mer formation to those of ImpC hydrolysis and the 3-mer and 4-mer formation decrease with an increase in temperature, which is attributed to the enthalpy and entropy changes for the formation of the 2-mer. This trend resembles the case of the template-directed formation of oligo(G) on a poly(C) template but is different from the Pb (2+)-ion-catalyzed oligo(C) formation. According to the kinetics and activation parameter analyses regarding the clay reaction and other prebiotic polymerase models, the possible pathways for the oligonucleotide formation are discussed and compared.     

Absolute potassium cation affinities (PCAs) in the gas phase

The potassium cation affinities (PCAs) of 136 ligands (20 classes) in the gas phase were established by hybrid density functional theory calculations (B3-LYP with the 6-311+G(3df,2p) basis set). For these 136 ligands, 70 experimental values are available for comparison. Except for five specific PCA values-those of phenylalanine, cytosine, guanine, adenine (kinetic-method measurement), and Me(2)SO (by high-pressure mass spectrometric equilibrium measurement)-our theoretical estimates and the experimental affinities are in excellent agreement (mean absolute deviation (MAD) of 4.5 kJ mol(-1)). Comparisons with previously reported theoretical PCAs are also made. The effect of substituents on the modes of binding and the PCAs of unsubstituted parent ligands are discussed. Linear relations between Li+/Na+ and K+ affinities suggest that for the wide range of ligands studied here, the nature of binding between the cations and a given ligand is similar, and this allows the estimation of PCAs from known Li+ and/or Na+ affinities. Furthermore, empirical equations relating the PCAs of ligands with their dipole moments, polarizabilities (or molecular weights), and the number of binding sites were established. Such equations offer a simple method for estimating the PCAs of ligands not included in the present study.     

Competition between pi and non-pi cation-binding sites in aromatic amino acids: a theoretical study of alkali metal cation (Li+, Na+, K+)-phenylalanine complexes

To understand the cation-pi interaction in aromatic amino acids and peptides, the binding of M(+) (where M(+) = Li(+), Na(+), and K(+)) to phenylalanine (Phe) is studied at the best level of density functional theory reported so far. The different modes of M(+) binding show the same order of binding affinity (Li(+)>Na(+)>K(+)), in the approximate ratio of 2.2:1.5:1.0. The most stable binding mode is one in which the M(+) is stabilized by a tridentate interaction between the cation and the carbonyl oxygen (O[double bond]C), amino nitrogen (--NH(2)), and aromatic pi ring; the absolute Li(+), Na(+), and K(+) affinities are estimated theoretically to be 275, 201, and 141 kJ mol(-1), respectively. Factors affecting the relative stabilities of various M(+)-Phe binding modes and conformers have been identified, with ion-dipole interaction playing an important role. We found that the trend of pi and non-pi cation bonding distances (Na(+)-pi>Na(+)-N>Na(+)-O and K(+)-pi>K(+)-N>K(+)-O) in our theoretical Na(+)/K(+)-Phe structures are in agreement with the reported X-ray crystal structures of model synthetic receptors (sodium and potassium bound lariat ether complexes), even though the average alkali metal cation-pi distance found in the crystal structures is longer. This difference between the solid and the gas-phase structures can be reconciled by taking the higher coordination number of the cations in the lariat ether complexes into account.     

Stability analysis of the two rotational isomers of meta-fluorobenzaldehyde in the S0, S1, and S2 electronic states

For a determination of the stabilization energy between the two rotational isomers of m-fluorobenzaldehyde, the S(1,2)<--S0 absorption spectra were observed in fluid n-hexane solutions at 293 and 198 K. After employing a simulation method for the spectra, we succeeded in determining the stabilization energies in the ground and the relevant excited state at the same time. The energy was estimated to be 1.7 +/- 0.5 kJ mol(-1) for S0 and also for S1 while it was 2.9 +/- 0.5 kJ mol(-1) for S2. Ab initio calculations at MP2/6-311G** computational level predicted that the O-cis form in the S0 state is more stable by 1.9 +/- 0.5 kJ mol(-1) than the counterpart rotamer, O-trans form. In summary, a schematic energy level diagram of the two rotational isomers will be illustrated for the S0, S1, and S2 states in the fluid system.     

Enthalpies of formation of gas-phase N3, N3-, N5+, and N5- from Ab initio molecular orbital theory, stability predictions for N5(+)N3(-) and N5(+)N5(-), and experimental evidence for the instability of N5(+)N3(-)

Ab initio molecular orbital theory has been used to calculate accurate enthalpies of formation and adiabatic electron affinities or ionization potentials for N3, N3-, N5+, and N5- from total atomization energies. The calculated heats of formation of the gas-phase molecules/ions at 0 K are DeltaHf(N3(2Pi)) = 109.2, DeltaHf(N3-(1sigma+)) = 47.4, DeltaHf(N5-(1A1')) = 62.3, and DeltaHf(N5+(1A1)) = 353.3 kcal/mol with an estimated error bar of +/-1 kcal/mol. For comparison purposes, the error in the calculated bond energy for N2 is 0.72 kcal/mol. Born-Haber cycle calculations, using estimated lattice energies and the adiabatic ionization potentials of the anions and electron affinities of the cations, enable reliable stability predictions for the hypothetical N5(+)N3(-) and N5(+)N5(-) salts. The calculations show that neither salt can be stabilized and that both should decompose spontaneously into N3 radicals and N2. This conclusion was experimentally confirmed for the N5(+)N3(-) salt by low-temperature metathetical reactions between N5SbF6 and alkali metal azides in different solvents, resulting in violent reactions with spontaneous nitrogen evolution. It is emphasized that one needs to use adiabatic ionization potentials and electron affinities instead of vertical potentials and affinities for salt stability predictions when the formed radicals are not vibrationally stable. This is the case for the N5 radicals where the energy difference between vertical and adiabatic potentials amounts to about 100 kcal/mol per N5.     

Enthalpy of formation of the cyclopentadienyl radical: photoacoustic calorimetry and ab initio studies

The gas-phase C-H bond dissociation enthalpy (BDE) in 1,3-cyclopentadiene has been determined by time-resolved photoacoustic calorimetry (TR-PAC) as 358 +/- 7 kJ mol(-1). Theoretical results from ab initio complete basis-set approaches, including the composite CBS-Q and CBS-QB3 procedures, and basis-set extrapolated coupled-cluster calculations (CCSD(T)) are reported. The CCSD(T) prediction for the C-H BDE of 1,3-cyclopentadiene (353.3 kJ mol(-1)) is in good agreement with the TR-PAC result. On the basis of the experimental and the theoretical values obtained, we recommend 355 +/- 8 kJ mol(-1) for the C-H BDE of 1,3-cyclopentadiene and 271 +/- 8 kJ mol(-1) for the enthalpy of formation of cyclopentadienyl radical.     

Synthesis of [(MeCyt)2H]I-structure and stability of a dimeric threefold hydrogen-bonded 1-methylcytosinium 1-methylcytosine cation

Reaction of trimethylsilyl-protected cytosine with methyl iodide afforded N1-methylated product. Subsequent treatment with ethanol resulted in cleavage of the protection group forming [(MeCyt)2H]I (4). Identity of was confirmed by microanalysis, mass spectrometry, 1H and 13C NMR spectroscopy and by single-crystal X-ray diffraction analysis. Crystals of consist of dimeric [(MeCyt)2H]+ cations and I- anions. These ions are arranged in the crystal such that there is a strong base stacking (mean stacking distance 3,467 angstroms) and, furthermore, pi interactions between I- and cytosine rings (mean distance 3,737 angstroms). The dimeric [(MeCyt)2H]+ cations are centrosymmetric having three strong hydrogen bonds, namely two terminal N4-H...O' ones (N4...O' 2.815(4) angstroms) and a central N3-H...N3' (N3...N3' 2.813(4) angstroms) one. Quantum chemical calculations on the DFT level of theory show that the gas phase structure of the dimeric cation exhibits two different terminal N-HO hydrogen bonds, a stronger (N4...O' 2.722 angstroms) and a weaker one (N4'...O 2.960 angstroms). The central N3-HN3[prime or minute] hydrogen bond (N3...N3' 2.852 angstroms) was characterized to have an unsymmetrically located proton and a typical double minimum potential with a very low activation barrier. The interaction energy between [(MeCyt)H]+ and MeCyt yielding [(MeCyt)2H]+ was calculated to be -42.4 kcal mol(-1)(ZPE and BSSE corrected). Comparison with the interaction energy (calculated on the same level of the theory) between cytosine and guanine yielding the triply hydrogen-bonded Watson-Crick dimer (-24.2 kcal mol(-1)) revealed a much higher stability of the hydrogen bonds in [(MeCyt)2H]+.     

Stoichiometries and thermodynamic stabilities for aqueous sulfate complexes of U(VI)

The formation constants of UO2SO4 (aq), UO2(SO4)2(2-), and UO2(SO4)3(4-) were measured in aqueous solutions from 10 to 75 degrees C by time-resolved laser-induced fluorescence spectroscopy (TRLFS). A constant enthalpy of reaction approach was satisfactorily used to fit the thermodynamic parameters of stepwise complex formation reactions in a 0.1 M Na(+) ionic medium: log 10 K 1(25 degrees C) = 2.45 +/- 0.05, Delta r H1 = 29.1 +/- 4.0 kJ x mol(-1), log10 K2(25 degrees C) = 1.03 +/- 0.04, and Delta r H2 = 16.6 +/- 4.5 kJ x mol(-1). While the enthalpy of the UO2(SO4)2(2-) formation reaction is in good agreement with calorimetric data, that for UO2SO4 (aq) is higher than other values by a few kilojoules per mole. Incomplete knowledge of the speciation may have led to an underestimation of Delta r H1 in previous calorimetric studies. In fact, one of the published calorimetric determinations of Delta r H1 is here supported by the TRLFS results only when reinterpreted with a more correct equilibrium constant value, which shifts the fitted Delta r H1 value up by 9 kJ x mol(-1). UO2(SO 4) 3 (4-) was evidenced in a 3 M Na (+) ionic medium: log10 K3(25 degrees C) = 0.76 +/- 0.20 and Delta r H3 = 11 +/- 8 kJ x mol(-1) were obtained. The fluorescence features of the sulfate complexes were observed to depend on the ionic conditions. Changes in the coordination mode (mono- and bidentate) of the sulfate ligands may explain these observations, in line with recent structural data.     

亲水作用色谱法测定组织中全基因组DNA甲基化水平

建立了亲水作用色谱(HILIC)测定组织中全基因组DNA甲基化水平的方法。采用苯酚-氯仿提取组织中的DNA,提取的DNA用88%甲酸在140 ℃下裂解,经N2吹干后,加乙腈-水(9:1, v/v)溶解,用Waters BEH HILIC柱进行分离,在277 nm波长下检测胞嘧啶(Cyt)及5-甲基胞嘧啶(5-mCyt)含量。结果表明,以乙腈-10 mmol/L甲酸铵溶液(94:6, v/v)为流动相,流速为0.5 mL/min, Cyt与5-mCyt分离较好,保留时间分别为2.6与3.1 min。胞嘧啶的线性范围为1～900 μmol/L,相关系数为0.9999; 5-甲基胞嘧啶的线性范围为1～64 μmol/L,相关系数为0.9998。胞嘧啶和5-甲基胞嘧啶的检出限为54 nmol/L(柱中为0.54 pmol),定量限为250 nmol/L(柱中为2.5 pmol);在5～900 μmol/L的添加水平下,胞嘧啶和5-甲基胞嘧啶的平均加标回收率为94.7%～100.5%,相对标准偏差小于1.48%。用该方法检测了结肠癌组织中DNA甲基化水平,结果显示该癌组织中全基因组的DNA甲基化均值为4.0%。该方法快速、简单,稳定性好,灵敏度较高,能满足全基因组DNA甲基化的检测要求。     

Experimental and theoretical studies of potassium cation interactions with the acidic amino acids and their amide derivatives

The binding of K(+) to aspartic acid (Asp), glutamic acid (Glu), asparagine (Asn), and glutamine (Gln) is examined in detail by studying the collision-induced dissociation (CID) of the four potassium cation-bound amino acid complexes with Xe using a guided ion beam tandem mass spectrometer (GIBMS). Formed by electrospray ionization, these complexes have energy-dependent CID cross sections that are analyzed to provide 0 K bond energies after accounting for unimolecular decay rates, internal energy of reactant ions, and multiple ion-molecule collisions. Quantum chemical calculations for a number of geometric conformations of each K(+)(L) complex are determined at the B3LYP/6-311+G(d,p) level with single-point energies calculated at B3LYP, B3P86, and MP2(full) levels using a 6-311+G(2d,2p) basis set. Theoretical bond dissociation energies are in good agreement with the experimental values. This coordinated examination of both experimental work and quantum chemical calculations allows for a comprehensive understanding of the molecular interactions of K(+) with the Asx and Glx amino acids. K(+) binding affinities for the amide complexes are systematically stronger than those for the acid complexes by 9+/-1 kJ/mol, which is attributed to an inductive effect of the OH group in the carboxylic acid side chain. Additionally, the K(+) binding affinity for the longer-chain amino acids (Glx) is enhanced by 5+/-1 kJ/mol compared to the shorter-chain Asx because steric effects are reduced. Further, a detailed comparison between experimental and theoretical results reveals interesting differences in the binding of K(+) and Na(+) to these amino acids.     

Proton affinity of canavanine and canaline, oxyanalogues of arginine and ornithine, from the extended kinetic method

The absolute proton affinities of the nonprotein amino acids canavanine and canaline have been determined using the extended kinetic method in an electrospray ionization quadrupole ion trap instrument. Canavanine results from the substitution of an oxygen atom for the delta-CH2 group in the side chain of the protein amino acid arginine, whereas canaline results from a similar substitution at the delta-CH2 group in the side chain of ornithine. Absolute proton affinities of 1001+/-9 and 950+/-7 kJ/mol are obtained for canavanine and canaline, respectively. For canaline, this proton affinity is in excellent agreement with theoretical predictions obtained using the hybrid density functional theory method B3LYP/6-311++G**//B3LYP/6-31+G*. For canavanine, theory predicts a somewhat larger proton affinity of 1015 kJ/mol. Oxygen atom substitution in these nonprotein amino acids results in a decrease in their proton affinities of 40-50 kJ/mol compared to arginine and ornithine.     

A restricted-open-shell complete-basis-set model chemistry

A restricted-open-shell model chemistry based on the complete basis set-quadratic Becke3 (CBS-QB3) model is formulated and denoted ROCBS-QB3. As the name implies, this method uses spin-restricted wave functions, both for the direct calculations of the various components of the electronic energy and for extrapolating the correlation energy to the complete-basis-set limit. These modifications eliminate the need for empirical corrections that are incorporated in standard CBS-QB3 to compensate for spin contamination when spin-unrestricted wave functions are used. We employ an initial test set of 19 severely spin-contaminated species including doublet radicals and both singlet and triplet biradicals. The mean absolute deviation (MAD) from experiment for the new ROCBS-QB3 model (3.6+/-1.5 kJ mol(-1)) is slightly smaller than that of the standard unrestricted CBS-QB3 version (4.8+/-1.5 kJ mol(-1)) and substantially smaller than the MAD for the unrestricted CBS-QB3 before inclusion of the spin correction (16.1+/-1.5 kJ mol(-1)). However, when applied to calculate the heats of formation at 298 K for the moderately spin-contaminated radicals in the G2/97 test set, ROCBS-QB3 does not perform quite as well as the standard unrestricted CBS-QB3, with a MAD from experiment of 3.8+/-1.6 kJ mol(-1) (compared with 2.9+/-1.6 kJ mol(-1) for standard CBS-QB3). ROCBS-QB3 performs marginally better than standard CBS-QB3 for the G2/97 set of ionization energies with a MAD of 4.1+/-0.1 kJ mol(-1) (compared with 4.4+/-0.1 kJ mol(-1)) and electron affinities with a MAD of 3.9+/-0.2 kJ mol(-1) (compared with 4.3+/-0.2 kJ mol(-1)), but the differences in MAD values are comparable to the experimental uncertainties. Our overall conclusion is that ROCBS-QB3 eliminates the spin correction in standard CBS-QB3 with no loss in accuracy.     

Inverse hydrogen bonds between XeH2 and hydride and fluoride derivatives of Li, Be, Na and Mg

A theoretical study of the inverse hydrogen bonds complexes formed by the XeH₂ molecule and hydride and fluoride derivatives of Li, Be, Na and Mg has been carried out by means of DFT (B3LYP/DGDZVP) and ab initio [MP2/DGDZVP and MP2/LJ18/6-311++G(2d,2p)] calculations. The complexes obtained present interaction energies up to ?81 kJ/mol. The analysis of the electron density shows electron transfer from the XeH₂ to the electron acceptor molecules. The calculated absolute chemical shieldings show the high sensitivity of the xenon atom upon complexation.     

High-accuracy extrapolated ab initio thermochemistry of vinyl chloride

Applying a modified "high accuracy extrapolated ab initio thermochemistry" (HEAT) scheme, the standard heat of formation of vinyl chloride at 0 K is computed to be 29.79 +/- 1 kJ/mol and at 298.15 K to be 20.9 +/- 2 kJ/mol, thus resolving earlier discrepancies among the available experimental values, which span a range from 21 up to 38 kJ/mol. The enthalpies of the reactions C2H4 + Cl2 --> CH2CHCl + HCl and C2H2 + HCl --> CH2CHCl at 298.15 K are determined to be -123.0 and -113.9 +/- 2 kJ/mol, respectively.     

New insight into the substituent effects on the hydrolytic deamination of saturated and unsaturated cytosine

Ab initio calculations were carried out to understand the effect of electron donating groups (EDG) and electron withdrawing groups (EWG) at the C5 position of cytosine (Cyt) and saturated cytosine (H₂Cyt) of the deamination reaction. Geometries of the reactants, transition states, intermediates, and products were fully optimized at the B3LYP/6-31G(d,p) level in the gas phase as this level of theory has been found to agree very well with G3 theories. Activation energies, enthalpies, and Gibbs energies of activation along with the thermodynamic properties (ΔE, ΔH, and ΔG) of each reaction were calculated. A plot of the Gibbs energies of activation (ΔG^‡) for C5 substituted Cyt and H₂Cyt against the Hammett σ-constants reveal a good linear relationship. In general, both EDG and EWG substituents at the C5 position in Cyt results in higher ΔG^‡ and lower σ values compared to those of H₂Cyt deamination reactions. C5 alkyl substituents ( H,  CH₃,  CH₂CH₃,  CH₂CH₂CH₃) increase ΔG^‡ values for Cyt, while the same substituents decrease ΔG^‡ values for H₂Cyt which is likely due to steric effects. However, the Hammett σ-constants were found to decrease at the C5 position of cytosine (Cyt) and saturated cytosine (H2Cyt) on the deamination reaction. Both ΔG^‡ and σ values decrease for the substituents Cl and Br in the Cyt reaction, while ΔG^‡ values increase and σ decrease in the H₂Cyt reaction. This may be due to high polarizability of bromine which results in a greater stabilization of the transition state in the case of bromine compared to chlorine. Regardless of the substituent at C5, the positive charge on C4 is greater in the TS compared to the reactant complex for both the Cyt and H₂Cyt. Moreover, as the charges on C4 in the TS increase compared to reactant, ΔG^‡ also increase for the C5 alkyl substituents ( H,  CH₃,  CH₂CH₃,  CH₂CH₂CH₃) in Cyt, while ΔG^‡ decrease in H₂Cyt. In addition, analysis of the frontier MO energies for the transition state structures shows that there is a correlation between the energy of the HOMO–LUMO gap and activation energies.     

Experimental and theoretical studies of sodium cation interactions with the acidic amino acids and their amide derivatives

The binding of Na+ to aspartic acid (Asp), glutamic acid (Glu), asparagine (Asn), and glutamine (Gln) is examined in detail by studying the collision-induced dissociation (CID) of the four sodiated amino acid complexes with Xe using a guided ion beam tandem mass spectrometer (GIBMS). Analysis of the energy-dependent CID cross sections provides 0 K sodium cation affinities for the complexes after accounting for unimolecular decay rates, internal energy of the reactant ions, and multiple ion-molecule collisions. Quantum chemical calculations for a number of geometric conformations of each Na+(L) complex are determined at the B3LYP/6-311+G(d,p) level with single-point energies calculated at MP2(full), B3LYP, and B3P86 levels using a 6-311+G(2d,2p) basis set. This coordinated examination of both experimental work and quantum chemical calculations allows the energetic contributions of individual functionalities as well as steric influences of relative chain lengths to be thoroughly explored. Na+ binding affinities for the amide complexes are systematically stronger than those for the acid complexes by 14 +/- 1 kJ/mol, which is attributed to an inductive effect of the OH group in the carboxylic acid side chain. Additionally, the Na+ binding affinity for the longer-chain amino acids (Glx) is enhanced by 4 +/- 1 kJ/mol compared to the shorter-chain Asx because steric effects are reduced.     

Experimental validation of Gaussian-3 lithium cation affinities of amides: implications for the gas-phase lithium cation basicity scale.

Using a refined Gaussian-3 (G3) protocol, the highest level of ab initio calculations reported so far, we have established the Li+ cation binding enthalpy (affinity) at 0 K (in kJ mol-1) for formamide (195.7), N-methylformamide (209.2), N,N'-dimethylformamide (220.0), acetamide (211.7), N-methylacetamide (222.5), and N,N'-dimethylacetamide (230.1), with an estimated maximum uncertainty of +/-8 kJ mol-1. With these six theoretical lithium cation binding affinities as reference values, the absolute Li+ affinities of imidazole and dimethoxyethane were determined by the extended kinetic method, and by adopting the statistical data treatment protocol recently proposed by Armentrout. The Li+ affinities obtained for these two ligands are in good agreement (within 6 kJ mol-1) with recent values determined by the threshold collision-induced dissociation method, and consistent with the Li+ basicity values first reported by Taft and co-workers in 1990. Our study confirms that the previously suggested, and recently implemented, downward revision of Taft's original basicity scale by 10.9 kJ mol-1 is justified for ligands with revised basicities less than 151 kJ mol-1. However, for selected ligands with Li+ basicities greater than 151 kJ mol-1, including some of the six amides studied in this work, the reported discrepancy between theoretical and experimental estimates in the revised Li+ basicity scale of Burk et al. is likely to arise from experimental uncertainties.