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Naturally occurring and chemically engineered modifications are among the most powerful strategies explored for fine-tuning the conformational characteristics and intrinsic stability of nucleic acids topologies. Modifications at the 2′-position of the ribose or 2′-deoxyribose moieties differentiate nucleic acid structures and have a significant impact on their electronic properties and base-pairing interactions. 2′-O-Methylation, a common post-transcriptional modification of tRNA, is directly involved in modulating specific anticodon–codon base-pairing interactions. 2′-Fluorinated and arabino nucleosides possess novel and beneficial medicinal properties and find use as therapeutics for treating viral diseases and cancer. However, the potential to deploy 2′-modified cytidine chemistries for tuning i-motif stability is largely unknown. To address this knowledge gap, the effects of 2′-modifications including O-methylation, fluorination, and stereochemical inversion on the base-pairing interactions of protonated cytidine nucleoside analogue base pairs, the core stabilizing interactions of i-motif structures, are examined using complementary threshold collision-induced dissociation techniques and computational methods. The 2′-modified cytidine nucleoside analogues investigated here include 2′-O-methylcytidine, 2′-fluoro-2′-deoxycytidine, arabinofuranosylcytosine, 2′-fluoro-arabinofuranosylcytosine, and 2′,2′-difluoro-2′-deoxycytidine. All five 2′-modifications examined here are found to enhance the base-pairing interactions relative to the canonical DNA and RNA cytidine nucleosides with the greatest enhancements arising from 2′-O-methylation and 2′,2′-difluorination, suggesting that these modifications should well be tolerated in the narrow grooves of i-motif conformations. [ABSTRACT FROM AUTHOR]

DNA nanotechnology has been employed to develop devices based on i-motif structures. The protonated cytosine-cytosine base pairs that stabilize i-motif conformations are favored under slightly acidic conditions. This unique property has enabled development of the first DNA molecular motor driven by pH changes. The ability to alter the stability and pH transition range of such DNA molecular motors is desirable. Understanding how i-motif structures are influenced by modifications, and which modifications enhance stability and/or affect the pH characteristics, are therefore of great interest. Here, the influence of 5-halogenation of the cytosine nucleobases on the base pairing of protonated cytidine nucleoside analogue base pairs is examined using complementary threshold collision-induced dissociation techniques and computational methods. The nucleoside analogues examined here include the 5-halogenated forms of the canonical DNA and RNA cytidine nucleosides. Comparisons among these systems and to the analogous canonical base pairs previously examined enable the influence of 5-halogenation and the 2′-hydroxy substituent on the base pairing to be elucidated. 5-Halogenation of the cytosine nucleobases is found to enhance the strength of base pairing of DNA base pairs and generally weakens the base pairing for RNA base pairs. Trends in the strength of base pairing indicate that both inductive and polarizability effects influence the strength of base pairing. Overall, the present results suggest that 5‑halogenation, and in particular, 5-fluorination and 5-iodination, provide effective means of stabilizing DNA i-motif conformations for applications in nanotechnology, whereas only 5-iodination is effective for stabilizing RNA i-motif conformations but the enhancement in stability is less significant. [ABSTRACT FROM AUTHOR]

Threshold collision-induced dissociation of M(super +1) (adenine) with xenon is studied using guided ion beam mass spectrometry. Theoretical calculations on Cu(super +) indicate distinct differences in the binding site propensities of adenine to the alkali vs transition metal ions, a consequence of s-d sigma hybridization on the latter.

A theoretical and experimental investigation of the influence of halogenation on the properties of uracil and its noncovalent interactions with alkali metal ions is conducted. In addition, theoretical calculations are performed to examine the influence of halogenation on the acidities, proton affinities, and Watson-Crick base pairing energies.

IRMPD action spectroscopy studies of protonated 2'-deoxycytidine and cytidine, [dCyd+H]+ and [Cyd+H]+, have established that both N3 and O2 protonated conformers coexist in the gas phase. Threshold collision-induced dissociation (CID) of [dCyd+H]+ and [Cyd+H]+ is investigated here using guided ion beam tandem mass spectrometry techniques to elucidate the mechanisms and energetics for N-glycosidic bond cleavage. N-Glycosidic bond cleavage is observed as the major dissociation pathways resulting in competitive elimination of either protonated or neutral cytosine for both protonated cytosine nucleosides. Electronic structure calculations are performed to map the potential energy surfaces (PESs) for both N-glycosidic bond cleavage pathways observed. The molecular parameters derived from theoretical calculations are employed for thermochemical analysis of the energy-dependent CID data to determine the minimum energies required to cleave the N-glycosidic bond along each pathway. B3LYP and MP2(full) computed activation energies for N-glycosidic bond cleavage associated with elimination of protonated and neutral cytosine, respectively, are compared to measured values to evaluate the efficacy of these theoretical methods in describing the dissociation mechanisms and PESs for N-glycosidic bond cleavage. The 2'-hydroxyl of [Cyd+H]+ is found to enhance the stability of the N-glycosidic bond vs that of [dCyd+H]+. O2 protonation is found to control the threshold energies for N-glycosidic bond cleavage as loss of neutral cytosine from the O2 protonated conformers is found to require ~25 kJ/mol less energy than the N3 protonated analogues, and the activation energies and reaction enthalpies computed using B3LYP exhibit excellent agreement with the measured thresholds for the O2 protonated conformers. [ABSTRACT FROM AUTHOR]

In this review, noncovalent interactions of ions with neutral molecules are discussed. After defining the scope of the article, which excludes anionic and most protonated systems, methods associated with measuring thermodynamic information for such systems are briefly recounted. An extensive set of tables detailing available thermodynamic information for the noncovalent interactions of metal cations with a host of ligands is provided. Ligands include small molecules (H2, NH3, CO, CS, H2O, CH3CN, and others), organic ligands (O- and N-donors, crown ethers and related molecules, MALDI matrix molecules), π-ligands (alkenes, alkynes, benzene, and substituted benzenes), miscellaneous inorganic ligands, and biological systems (amino acids, peptides, sugars, nucleobases, nucleosides, and nucleotides). Hydration of metalated biological systems is also included along with selected proton-based systems: 18-crown-6 polyether with protonated peptides and base-pairing energies of nucleobases. In all cases, the literature thermochemistry is evaluated and, in many cases, reanchored or adjusted to 0 K bond dissociation energies. Trends in these values are discussed and related to a variety of simple molecular concepts. [ABSTRACT FROM AUTHOR]

Hypermethylation of cytosine in expanded (CCG)•(CGG) trinucleotide repeats results in Fragile X syndrome, the most common cause of inherited mental retardation. The (CCG)•(CGG) repeats adopt i-motif conformations that are preferentially stabilized by base-pairing interactions of protonated base pairs of cytosine. Here we investigate the effects of 5-methylation and the sugar moiety on the base-pairing energies (BPEs) of protonated cytosine base pairs by examining protonated nucleoside base pairs of 2′-deoxycytidine (dCyd) and 5-methyl-2′-deoxycytidine (mdCyd) using threshold collision-induced dissociation techniques. 5-Methylation of a single or both cytosine residues leads to very small change in the BPE. However, the accumulated effect may be dramatic in diseased state trinucleotide repeats where many methylated base pairs may be present. The BPEs of the protonated nucleoside base pairs examined here significantly exceed those of Watson-Crick dGuo•dCyd and neutral dCyd•dCyd base pairs, such that these base-pairing interactions provide the major forces responsible for stabilization of DNA i-motif conformations. Compared with isolated protonated nucleobase pairs of cytosine and 1-methylcytosine, the 2′-deoxyribose sugar produces an effect similar to the 1-methyl substituent, and leads to a slight decrease in the BPE. These results suggest that the base-pairing interactions may be slightly weaker in nucleic acids, but that the extended backbone is likely to exert a relatively small effect on the total BPE. The proton affinity (PA) of mdCyd is also determined by competitive analysis of the primary dissociation pathways that occur in parallel for the protonated (mdCyd)H(dCyd) nucleoside base pair and the absolute PA of dCyd previously reported. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Theground-state structures and sequential binding energies ofthe late first-row divalent transition metal cations to pyridine (Pyr)are determined using density functional theory (DFT) methods. Fivelate first-row transition metal cations in their +2 oxidation statesare examined including: Fe2+, Co2+, Ni2+, Cu2+, and Zn2+. Calculations at B3LYP, BHandHLYP,and M06 levels of theory using 6-31G* and 6-311+G(2d,2p) basis setsare employed to determine the structures and theoretical estimatesfor the sequential binding energies of the M2+(Pyr)xcomplexes, where x= 1–6,respectively. Structures of the Ca2+(Pyr)xcomplexes are compared to those for the M2+(Pyr)xcomplexes of Fe2+, Co2+, Ni2+, Cu2+, and Zn2+to furtherassess the effects of the d-orbital occupation on the preferred bindinggeometries. The B3LYP, BHandHLYP, and M06 levels of theory yield verysimilar geometries for the analogous M2+(Pyr)xcomplexes. The overall trends in the sequentialBDEs for all five metal cations at all three levels of theory examinedare highly parallel, and are determined by a balance of the effectsof the valence electronic configuration and hybridization of the metalcation, but are also influenced by repulsive ligand–ligandinteractions. Present results for the M2+(Pyr)xcomplexes are compared to the analogous complexesof the late first-row monovalent transition metal cations, Co+, Ni+, Cu+, and Zn+previouslyinvestigated to assess the effect of the charge/oxidation state onthe structures and sequential binding energies. Trends in the sequentialbinding energies of the M2+(Pyr)xcomplexes are also compared to the analogous M2+(water)x, M2+(imidazole)x, M2+(2,2′-bipyridine)x, and M2+(1,10-phenanthroline)xcomplexes. [ABSTRACT FROM AUTHOR]

Threshold collision-induced dissociation(CID) of alkali metalcation–hexacyclen (ha18C6) complexes, M+(ha18C6),with xenon is studied using guided ion beam tandem mass spectrometrytechniques. The alkali metal cations examined here include: Na+, K+, Rb+, and Cs+. In allcases, M+is the only product observed, corresponding toendothermic loss of the intact ha18C6 ligand. The cross-section thresholdsare analyzed to extract zero and 298 K M+–ha18C6bond dissociation energies (BDEs) after properly accounting for theeffects of multiple M+(ha18C6)–Xe collisions, thekinetic and internal energy distributions of the M+(ha18C6)and Xe reactants, and the lifetimes for dissociation of the activatedM+(ha18C6) complexes. Ab initio and density functionaltheory calculations are used to determine the structures of ha18C6and the M+(ha18C6) complexes, provide molecular constantsnecessary for the thermodynamic analysis of the energy–resolvedCID data, and theoretical estimates for the M+–ha18C6BDEs. Calculations using a polarizable continuum model are also performedto examine solvent effects on the binding. In the absence of solvent,the M+–ha18C6 BDEs decrease as the size of the alkalimetal cation increases, consistent with the noncovalent nature ofthe binding in these complexes. However, in the presence of solvent,the ha18C6 ligand exhibits selectivity for K+over theother alkali metal cations. The M+(ha18C6) structures andBDEs are compared to those previously reported for the analogous M+(18-crown-6) and M+(cyclen) complexes to examinethe effects of the nature of the donor atom (N versus O) and the numberdonor atoms (six vs four) on the nature and strength of binding. [ABSTRACT FROM AUTHOR]

The DNA i-motif conformation was discovered in (CCG)•(CGG)n trinucleotide repeats, which are associated with fragile X syndrome, the most widespread inherited cause of mental retardation in humans. The DNA i-motif is a four-stranded structure whose strands are held together by proton-bound dimers of cytosine (C+•C). The stronger base-pairing interactions in C+•C proton-bound dimers as compared to Watson-Crick G•C base pairs are the major forces responsible for stabilization of i-motif conformations. Methylation of cytosine results in silencing of the FMR1 gene and causes fragile X syndrome. However, the influence of methylation or other modifications such as halogenation of cytosine on the base-pairing energies (BPEs) in the i-motif remains elusive. To address this, proton-bound heterodimers of cytosine and 5-methylcytosine, 5-fluorocytosine, 5-bromocytosine, and 5-iodocytosine are probed in detail. Experimentally, the BPEs of proton-bound heterodimers of cytosine and modified cytosines are determined using threshold collision-induced dissociation (TCID) techniques. All modifications at the 5-position of cytosine are found to lower the BPE and therefore would tend to destabilize DNA i-motif conformations. However, the BPEs in these proton-bound heterodimers still significantly exceed those of the Watson-Crick G•C and neutral C•C base pairs, suggesting that C+•C mismatches are still energetically favored such that i-motif conformations are preserved. Excellent agreement between TCID measured BPEs and B3LYP calculated values is found with the def2-TZVPPD and 6-311+G(2d,2p) basis sets, suggesting that calculations at these levels of theory can be employed to provide reliable energetic predictions for related systems. [ABSTRACT FROM AUTHOR]

Absolute 18-crown-6 (18C6) binding affinities of four protonated acetylated amino acids (AcAAs) are determined using guided ion beam tandem mass spectrometry techniques. The AcAAs examined in this work include: N-terminal acetylated lysine (N-AcLys), histidine (N-AcHis), and arginine (N-AcArg) as well as side chain acetylated lysine (N-AcLys). The kinetic-energy-dependent cross sections for collision-induced dissociation (CID) of the (AcAA)H(18C6) complexes are analyzed using an empirical threshold law to extract absolute 0 and 298 K (AcAA)H−18C6 bond dissociation energies (BDEs) after accounting for the effects of multiple collisions, kinetic and internal energy distributions of the reactants, and unimolecular dissociation lifetimes. Theoretical electronic structure calculations are performed to determine stable geometries and energetics for neutral and protonated 18C6 and the AcAAs as well as the proton bound complexes of these species, (AcAA)H(18C6), at the B3LYP/6-311+G(2d,2p)//B3LYP/6-31 G* and M06/6-311+G(2d,2p)//B3LYP/6-31G* levels of theory. For all four (AcAA)H(18C6) complexes, loss of neutral 18C6 corresponds to the most favorable dissociation pathway. At elevated energies, products arising from sequential dissociation of the primary CID product, H(AcAA), are also observed. Protonated N-AcLys exhibits a greater 18C6 binding affinity than other protonated N-AcAAs, suggesting that the side chains of Lys residues are the preferred binding sites for 18C6 complexation to peptides and proteins. N-AcLys exhibits a greater 18C6 binding affinity than N-AcLys, suggesting that binding of 18C6 to the side chain of Lys residues is more favorable than to the N-terminal amino group of Lys. [ABSTRACT FROM AUTHOR]

The proton affinity (PA) of 18-crown-6 (18C6) is determined using competitive threshold collision-induced dissociation (TCID) techniques. The PA of 18C6 is derived from four thermochemical cycles involving the relative thresholds for production of the protonated bases, H+(B), and protonated crown, H+(18C6), from the collision-induced dissociation (CID) of four proton bound heterodimers, (B)H+(18C6). The bases examined include glycine (Gly), alanine (Ala), imidazole (Imid), and 4-methylimidazole (4MeImid). In all cases, CID pathways for the loss of intact B and 18C6 are observed in competition. Loss of intact 18C6 is observed as the lowest-energy CID pathway for the (Imid)H+(18C6) and (4MeImid)H+(18C6) complexes. In contrast, loss of intact Gly and Ala is observed as the lowest-energy CID pathway for the (Gly)H+(18C6) and (Ala)H+(18C6) complexes, respectively. Excellent agreement between the measured and calculated (B)H+-18C6 and (18C6)H+-B bond dissociation energies (BDEs) is found with M06 theory, whereas B3LYP theory systematically underestimates these BDEs. On the basis of the relative TCID thresholds for the primary and competitive CID pathways, as well as the literature PAs of the bases, the PA of 18C6 is evaluated. The PA determined here for 18C6 exhibits excellent agreement with M06 and B3LYP theories, and very good agreement with the value reported by Meot-Ner determined using high pressure mass spectrometry (HPMS) techniques, suggesting that the PA of 18C6 reported in the NIST Webbook based on HPMS measurements by Kebarle and co-workers is overestimated. [ABSTRACT FROM AUTHOR]

Absolute 18-crown-6 (18C6) affinities of five amino acids (AAs) are determined using guided ion beam tandem mass spectrometry techniques. The AAs examined in this work include glycine (Gly), alanine (Ala), lysine (Lys), histidine (His), and arginine (Arg). Theoretical electronic structure calculations are performed to determine stable geometries and energetics for neutral and protonated 18C6 and the AAs as well as the proton bound complexes comprised of these species, (AA)H+(18C6). The proton affinities (PAs) of Gly and Ala are lower than the PA of 18C6, whereas the PAs of Lys, His, and Arg exceed that of 18C6. Therefore, the collision-induced dissociation (CID) behavior of the (AA)H+(18C6) complexes differs markedly across these systems. CID of the complexes to Gly and Ala produces H+(18C6) as the dominant and lowest energy pathway. At elevated energies, H+(AA) was produced in competition with H+(18C6) as a result of the relatively favorable entropy change in the formation of H+(AA). In contrast, CID of the complexes to the protonated basic AAs results in the formation of H+(AA) as the only direct CID product. H+(18C6) was not observed, even at elevated energies, as a result of unfavorable enthalpy and entropy change associated with its formation. Excellent agreement between the measured and calculated (AA)H+-18C6 bond dissociation energies (BDEs) is found with M06 theory for all complexes except (His)H+(18C6), where theory overestimates the strength of binding. In contrast, B3LYP theory significantly underestimates the (AA)H+-18C6 BDEs in all cases. Among the basic AAs, Lys exhibits the highest binding affinity for 18C6, suggesting that the side chains of Lys residues are the preferred binding site for 18C6 complexation in peptides and proteins. Gly and Ala exhibit greater 18C6 binding affinities than Lys, suggesting that the N-terminal amino group provides another favorable binding site for 18C6. Trends in the 18C6 binding affinities among the five AAs examined here exhibit an inverse correlation with the polarizability and proton affinity of the AA. Therefore, the ability of the N-terminal amino group to compete for 18C6 complexation is best for Gly and should become increasing less favorable as the size of the side chain substituent increases. [ABSTRACT FROM AUTHOR]

The sodium cation affinities of six commonly used MALDI matrices are determined here using guided ion beam tandem mass spectrometry techniques. The collision-induced dissociation behavior of six sodium cationized MALDI matrices, Na(MALDI), with Xe is studied as a function of kinetic energy. The MALDI matrices examined here include: nicotinic acid, quinoline, 3-aminoquinoline, 4-nitroaniline, picolinic acid, and 3-hydroxypicolinic acid. In all cases, the primary dissociation pathway corresponds to endothermic loss of the intact MALDI matrix. The cross section thresholds are interpreted to yield zero and 298 K Na−MALDI bond dissociation energies (BDEs), or sodium cation affinities, after accounting for the effects of multiple ion-neutral collisions, the kinetic and internal energy distributions of the reactants, and dissociation lifetimes. Density functional theory calculations at the B3LYP/6-311+G(2d,2p)//B3LYP/6-31G* and MP2(full)/6-311+G(2d,2p)//B3LYP/6-31G* levels of theory are used to characterized the structures and energetics for these systems. The calculated BDEs exhibit very good agreement with the measured values for most systems. The experimental and theoretical Na−MALDI BDEs determined here are compared with those previously measured by cation transfer equilibrium methods. [ABSTRACT FROM AUTHOR]

The binding interactions in complexes of Zn숫 nitrogendonor ligands, (N-L) = pyridine (x= 1–4), 4,4′-dipyridyl (x= 1–3),2,2′-dipyridyl (x= 1–2), and 1,10-phenanthroline(x= 1–2), are examined in detail. The bonddissociation energies (BDEs) for loss of an intact ligand from theZn(N-L)xcomplexesare reported. Experimental BDEs are obtained from thermochemical analysesof the threshold regions of the collision-induced dissociation crosssections of Zn(N-L)xcomplexes. Density functional theory calculations at the B3LYP/6-31G*level of theory are performed to determine stable structures of thesespecies and to provide molecular parameters needed for the thermochemicalanalysis of experimental data. Relative stabilities of the variousconformations of these N-donor ligands and theircomplexes to Zn well as theoretical BDEs are determinedfrom single point energy calculations at the B3LYP/6-311(2d,2p)and M06/6-311(2d,2p) levels of theory using the B3LYP/6-31G* optimizedgeometries. The experimental BDEs for the Zn(N-L)xcomplexes are in reasonably goodagreement with values derived from density functional theory calculations.BDEs derived from M06 calculations provide better agreement with themeasured values than those based on B3LYP calculations. Trends inthe sequential BDEs are explained in terms of sp polarization of Zn橷 repulsive ligand–ligand interactions. Comparisonsare made to the analogous Cu(N-L)xand Ni(N-L)xcomplexes previously studied. [ABSTRACT FROM AUTHOR]

Absolute 18-crown-6 (18C6) affinities of nine protonated peptidomimetic bases are determined using guided ion beam tandem mass spectrometry techniques. The bases (B) included in this work are mimics for the n-terminal amino group and the side chains of the basic amino acids, i.e., the favorable sites for binding of 18C6 to peptides and proteins. Isopropylamine is chosen as a mimic for the n-terminal amino group, imidazole and 4-methylimidazole are chosen as mimics for the side chain of histidine (His), 1-methylguanidine is chosen as a mimic for the side chain of arginine (Arg), and several primary amines including methylamine, ethylamine, n-propylamine, n-butylamine, and 1,5-diamino pentane as mimics for the side chain of lysine (Lys). Theoretical electronic structure calculations are performed to determine stable geometries and energetics for neutral and protonated 18C6 and the peptidomimetic bases, as well as the proton bound complexes comprised of these species, (B)H+(18C6). The measured 18C6 binding affinities of the Lys side chain mimics are larger than the measured binding affinities of the mimics for Arg and His. These results suggest that the Lys side chains should be the preferred binding sites for 18C6 complexation to peptides and proteins. Present results also suggest that competition between Arg or His and Lys for 18C6 is not significant. The mimic for the n-terminal amino group exhibits a measured binding affinity for 18C6 that is similar to or greater than that of the Lys side chain mimics. However, theory suggests that binding to n-terminal amino group mimic is weaker than that to all of the Lys mimics. These results suggest that the n-terminal amino group may compete with the Lys side chains for 18C6 complexation. [ABSTRACT FROM AUTHOR]

Threshold collision-induced dissociation techniques are employed to determine the activation energies (AEs) and bond dissociation energies (BDEs) of metal cation-triethyl phosphate complexes, M+(TEP), where M+ = Mg+, Al+, Cu+, and Zn+. Activated dissociation resulting in loss of ethene, C2H4, corresponds to the primary and lowest energy pathway for all four systems examined. Sequential loss of additional C2H4 molecules and loss of the intact TEP ligand is also observed at elevated energies. Theoretical calculations at the B3LYP/6-31Gª level of theory are used to determine the structures, vibrational frequencies, and rotational constants of neutral TEP and the M+(TEP) complexes, transition states, intermediates, and products of the activated dissociation of these complexes. Theoretical AEs and BDE5 are determined from single point energy calculations at the B3LYP/6-311 +G(2d,2p) level using the B3LYP/6-31Gª optimized geometries. The agreement between the calculated and measured AEs for elimination of C2H4 is excellent for all four systems. In contrast, less satisfactory agreement between theory and experiment is found for the M+-TEP BDEs and may indicate limitations in the competitive model used to analyze these high energy dissociation pathways. The influence of the valence orbital occupation of the metal cation on the binding and activation propensities for elimination of ethene from TEP is examined. The binding of metal cations to TEP is compared to that of the nucleobases to assess the binding preferences of metal cations to nucleic acids [ABSTRACT FROM AUTHOR]

Initiating the DNA base excision repair pathway, DNA glycosylases find and hydrolytically excise damaged bases from DNA. While some DNA glycosylases exhibit narrow specificity, others remove multiple forms of damage. Human thymine DNA glycosylase (hTDG) cleaves thymine from mutagenic G·T mispairs, recognizes many additional lesions, and has a strong preference for nucleobases paired with guanine rather than adenine. Yet, hTDG avoids cytosine, despite the million-fold excess of normal G·C pairs over G·T mispairs. The mechanism of this remarkable and essential specificity has remained obscure. Here, we examine the possibility that hTDG specificity depends on the stability of the scissile base-sugar bond by determining the maximal activity (kmax) against a series of nucleobases with varying leaving-group ability. We find that hTDG removes 5-fluorouracil 78-fold faster than uracil, and 5-chlorouracil, 572-fold faster than thymine, differences that can be attributed predominantly to leaving-group ability. Moreover, hTDG readily excises cytosine analogues with improved leaving ability, including 5-fluorocytosine, 5-bromocytosine, and 5-hydroxycytosine, indicating that cytosine has access to the active site. A plot of log(kmax) versus leaving-group pKa reveals a Brønsted-type linear free energy relationship with a large negative slope of βIg = -1.6 ± 0.2, consistent with a highly dissociative reaction mechanism. Further, we find that the hydrophobic active site of hTDG contributes to its specificity by enhancing the inherent differences in substrate reactivity. Thus, hTDG specificity depends on N-glycosidic bond stability, and the discrimination against cytosine is due largely to its very poor leaving ability rather than its exclusion from the active site. [ABSTRACT FROM AUTHOR]

Threshold collision-induced dissociation of M+(AAA) with Xe is studied using guided ion beam tandem mass spectrometry. M+ include the alkali metal ions Na+ and K+. The three aromatic amino acids are examined, AAA = phenylalanine, tyrosine, or tryptophan. In all cases, endothermic loss of the intact aromatic amino acid is the dominant reaction pathway. The threshold regions of the cross sections are interpreted to extract 0 and 298 K bond dissociation energies for the M+-AAA complexes after accounting for the effects of multiple ion-neutral collisions, internal energy of the reactant ions, and dissociation lifetimes. Density functional theory calculations at the B3LVP/6-31G* level of theory are used to determine the structures of the neutral aromatic amino acids and their complexes to Na+ and K+ and to provide molecular constants required for the thermochemical analysis of the experimental data. Theoretical bond dissociation energies are determined from single-point energy calculations at the B3LYP/6-31G ++G(3df,3pd) level using the B3LVP/6-31G* geometries. Good agreement between theory and experiment is found for all systems. The present results are compared to earlier studies of these systems performed via kinetic and equilibrium methods. The present results are also compared to the analogous Na+ and K+ complexes to glycine, benzene, phenol, and indole to elucidate the relative contributions that each of the functional components of these aromatic amino acids make to the overall binding in these complexes. [ABSTRACT FROM AUTHOR]