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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.

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) 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]

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]

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]

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.

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 B3LYP/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/6-311++G(3df,3pd) level using the B3LYP/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.