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The gas-phase structures of protonated unsymmetrical 1,1-dimethylhydrazine (UDMH) and the proton-bound dimers of UDMH and hydrazine are examined by infrared multiple photon dissociation (IRMPD) action spectroscopy utilizing light generated by a free electron laser and an optical parametric oscillator laser system. To identify the structures present in the experimental studies, the measured IRMPD spectra are compared to spectra calculated at the B3LYP-GD3BJ/6-311+G(d,p) level of theory. These comparisons show that protonated UDMH binds the proton at the methylated nitrogen atom (α) with two low-lying α conformers probably being populated. For (UDMH)2H+, the proton is shared between the methylated nitrogen atoms with several low-lying α conformers likely to be populated. Higher-lying conformers of (UDMH)2H+ in which the proton is shared between α and β (unmethylated) nitrogen atoms cannot be ruled out on the basis of the IRPMD spectrum. For (N2H4)2H+, there are four low-lying conformers that all reproduce the IRMPD spectrum reasonably well. As hydrazine and UDMH see usage as fuels for rocket engines, such spectra are potentially useful as a means of remotely monitoring rocket launches, especially in cases of unsuccessful launches where environmental hazards need to be assessed. [ABSTRACT FROM AUTHOR]

Cisplatin, (NH3)2PtCl2, has been known as a successful metal-based anticancer drug for more than half a century. Its analogue, Argplatin, arginine-linked cisplatin, (Arg)PtCl2, is being investigated because it exhibits reactivity towards DNA and RNA that differs from that of cisplatin. In order to understand the basis for its altered reactivity, the deprotonated and sodium cationized forms of Argplatin, [(Arg-H)PtCl2]− and [(Arg)PtCl2 + Na]+, are examined by infrared multiple photon dissociation (IRMPD) action spectroscopy in the IR fingerprint and hydrogen-stretching regions. Complementary electronic structure calculations are performed using density functional theory approaches to characterize the stable structures of these complexes and to predict their infrared spectra. Comparison of the theoretical IR spectra predicted for various stable conformations of these Argplatin complexes to their measured IRMPD spectra enables determination of the binding mode(s) of Arg to the Pt metal center to be identified. Arginine is found to bind to Pt in a bidentate fashion to the backbone amino nitrogen and carboxylate oxygen atoms in both the [(Arg-H)PtCl2]− and [(Arg)PtCl2 + Na]+ complexes, the NO− binding mode. The neutral side chain of Arg also interacts with the Pt center to achieve additional stabilization in the [(Arg-H)PtCl2]− complex. In contrast, Na+ binds to both chlorido ligands in the [(Arg)PtCl2 + Na]+ complex and the protonated side chain of Arg is stabilized via hydrogen-bonding interactions with the carboxylate moiety. These findings are consistent with condensed-phase results, indicating that the NO− binding mode of arginine to Pt is preserved in the electrospray ionization process even under variable pH and ionic strength. [ABSTRACT FROM AUTHOR]

Ionic liquids (ILs) exhibit unique properties that have led to their development and widespread use for a variety of applications. Development efforts have generally focused on achieving desired macroscopic properties via tuning of the IL through variation of the cations and anions. Both the macroscopic and microscopic properties of an IL influence its tunability and thus feasibility of use for selected applications. Works geared toward a microscopic understanding of the nature and strength of the intrinsic cation--anion interactions of ILs have been limited to date. Specifically, the intrinsic strength of the cation--anion interactions in ILs is largely unknown. In previous work, we employed threshold collision-induced dissociation (TCID) approaches supported and enhanced by electronic structure calculations to determine the bond dissociation energies (BDEs) and characterize the nature of the cation--anion interactions in a series of four 2 : 1 clusters of 1-alkyl-3-methylimidazolium cations with the hexafluorophosphate anion, [2Cnmim:PF6]+. To examine the effects of the 1-alkyl chain on the structure and energetics of binding, the cation was varied over the series: 1-ethyl-3-methylimidazolium, [C2mim]+, 1-butyl-3-methylimidazolium, [C4mim]+, 1-hexyl-3-methylimidazolium, [C6mim]+, and 1-octyl- 3-methylimidazolium, [C8mim]+. The variation in the strength of binding among these [2Cnmim:PF6]+ clusters was found to be similar in magnitude to the average experimental uncertainty in the measurements. To definitively establish an absolute order of binding among these [2Cnmim:PF6]+ clusters, we extend this work again using TCID and electronic structure theory approaches to include competitive binding studies of three mixed 2 : 1 clusters of 1-alkyl-3-methylimidazolium cations and the hexafluorophosphate anion, [Cn-2mim:PF6:Cnmim]+ for n = 4, 6, and 8. The absolute BDEs of these mixed [Cn-2mim:PF6:Cnmim]+ clusters as well as the absolute difference in the strength of the intrinsic binding interactions as a function of the cation are determined with significantly improved precision. By combining the thermochemical results of the previous independent and present competitive measurements, the BDEs of the [2Cnmim:PF6]+ clusters are both more accurately and more precisely determined. Comparisons are made to results for the analogous [2Cnmim:BF4]+ and [Cn-2mim:BF4:Cnmim]+ clusters previously examined to elucidate the effects of the [PF6]- and [BF4]- anions on the binding. [ABSTRACT FROM AUTHOR]

Imidazolium-based cations and the hexafluorophosphate anion are among the most commonly used ionic liquids (ILs). Yet, the nature and strength of the intrinsic cation–anion interactions, and how they influence the macroscopic properties of these ILs are still not well understood. Threshold collision-induced dissociation is utilized to determine the bond dissociation energies (BDEs) of the 2 : 1 clusters of 1-alkyl-3-methylimidazolium cations and the hexafluorophosphate anion, [2Cnmim:PF6]+. The cation, [Cnmim]+, is varied across the series, 1-ethyl-3-methylimidazolium [C2mim]+, 1-butyl-3-methylimidazolium [C4mim]+, 1-hexyl-3-methylimidazolium [C6mim]+, 1-octyl-3-methylimidazolium [C8mim]+, to examine the structural and energetic effects of the size of the 1-alkyl substituent of the cation on the binding to [PF6]−. Complementary electronic structure methods are employed for the [Cnmim]+ cations, (Cnmim:PF6) ion pairs, and [2Cnmim:PF6]+ clusters to elucidate details of the cation–anion interactions and their impact on structure and energetics. Multiple levels of theory are benchmarked with the measured BDEs including B3LYP, B3LYP-GD3BJ, and M06-2X each with the 6-311+G(d,p) basis set for geometry optimizations and frequency analyses and the 6-311+G(2d,2p) basis set for energetic determinations. The modest structural variation among the [Cnmim]+ cations produces only minor structural changes and variation in the measured BDEs of the [2Cnmim:PF6]+ clusters. Present results are compared to those previously reported for the analogous 1-alkyl-3-methylimidazolium tetrafluoroborate IL clusters to compare the effects of these anions on the nature and strength of the intrinsic binding interactions. [ABSTRACT FROM AUTHOR]

Complexes of 18-crown-6 ether (18C6) with four protonated amino acids (AAs) are examined using infrared multiple photon dissociation (IRMPD) action spectroscopy utilizing light generated by the infrared free electron laser at the Centre Laser Infrarouge d’Orsay (CLIO). The AAs examined in this work include glycine (Gly) and the three basic AAs: histidine (His), lysine (Lys), and arginine (Arg). To identify the (AA)H+(18C6) conformations present in the experimental studies, the measured IRMPD spectra are compared to spectra calculated at the B3LYP/6-311+G(d,p) level of theory. Relative energies of various conformers and isomers are provided by single point energy calculations carried out at the B3LYP, B3P86, M06, and MP2(full) levels using the 6-311+G(2p,2d) basis set. The comparisons between the IRMPD and theoretical IR spectra indicate that 18C6 binds to Gly and His via the protonated backbone amino group, whereas protonated Lys prefers binding via the protonated side-chain amino group. Results for Arg are less definitive with strong evidence for binding to the protonated guanidino side chain (the calculated ground conformer at most levels of theory), but contributions from backbone binding to a zwitterionic structure are likely. [ABSTRACT FROM AUTHOR]

The gas-phase conformations of the protonated forms of thymidine-5′-monophosphate and uridine-5′-monophosphate, [pdThd+H]+ and [pUrd+H]+, are investigated by infrared multiple photon dissociation (IRMPD) action spectroscopy and electronic structure calculations. The IRMPD action spectra of [pdThd+H]+ and [pUrd+H]+ are measured over the IR fingerprint and hydrogen-stretching regions using the FELIX free electron laser and an OPO/OPA laser system. Low-energy conformations of [pdThd+H]+ and [pUrd+H]+ and their relative stabilities are computed at the MP2(full)/6-311+G(2d,2p)//B3LYP/6-311+G(d,p) and B3LYP/6-311+G(2d,2p)//B3LYP/6-311+G(d,p) levels of theory. Comparisons of the measured IRMPD action spectra and B3LYP/6-311+G(d,p) linear IR spectra computed for the low-energy conformers indicate that the dominant conformers of [pdThd+H]+ and [pUrd+H]+ populated in the experiments are protonated at the phosphate oxo oxygen atom, with a syn nucleobase orientation that is stabilized by strong P=OH+…O2 and P–OH…O4′ hydrogen-bonding interactions, and C2′-endo sugar puckering. Minor abundance of conformers protonated at the O2 carbonyl of the nucleobase residue may also contribute for [pdThd+H]+, but do not appear to be important for [pUrd+H]+. Comparisons to previous IRMPD spectroscopy investigations of the protonated forms of thymidine and uridine, [dThd+H]+ and [Urd+H]+, and the deprotonated forms of pdThd and pUrd, [pdThd−H]− and [pUrd−H]−, provide insight into the effects of the phosphate moiety and protonation on the conformational features of the nucleobase and sugar moieties. Most interestingly, the thymine and uracil nucleobases remain in their canonical forms for [pdThd+H]+ and [pUrd+H]+, unlike [dThd+H]+ and [Urd+H]+, where protonation occurs on the nucleobases and induces tautomerization of the thymine and uracil residues. [ABSTRACT FROM AUTHOR]

Uridine (Urd) is one of the naturally occurring pyrimidine nucleosides of RNA. 2′-Deoxyuridine (dUrd) is a naturally occurring modified form of Urd, but is not one of the canonical DNA nucleosides. In order to understand the effects of sodium cationization on the conformations and energetics of Urd and dUrd, infrared multiple photon dissociation (IRMPD) action spectroscopy experiments and density functional theory (DFT) calculations are performed. By comparing the calculated IR spectra of [Urd+Na]+ and [dUrd+Na]+ with the measured IRMPD spectra, the stable low-energy conformers populated in the experiments are determined. Anti oriented bidentate O2 and O2′ binding conformers of [Urd+Na]+ are the dominant conformers populated in the experiments, whereas syn oriented tridentate O2, O4′, and O5′ binding conformers of [dUrd+Na]+ are dominantly populated in the experiments. The 2′-hydroxyl substituent of Urd stabilizes the anti oriented O2 binding conformers of [Urd+Na]+. Significant differences between the measured IRMPD and calculated IR spectra for complexes of [Urd+Na]+ and [dUrd+Na]+ involving minor tautomeric forms of the nucleobase make it obvious that none are populated in the experiments. Survival yield analyses based on energy-resolved collision-induced dissociation (ER-CID) experiments suggest that the relative stabilities of protonated and sodium cationized Urd and dUrd follow the order: [dUrd+H]+ ＜ [Urd+H]+ ＜ [dUrd+Na]+ ＜ [Urd+Na]+. The 2′-deoxy modification is found to weaken the glycosidic bond of dUrd versus that of Urd for the sodium cationized uridine nucleosides. [ABSTRACT FROM AUTHOR]

The gas-phase conformations of protonated uridine, [Urd+H]+, and its 2′-deoxy form, protonated 2′-deoxyuridine, [dUrd+H]+, have been examined in detail previously by infrared multiple photon dissociation action spectroscopy techniques. Both 2,4-dihydroxy tautomers and O4 protonated conformers of [Urd+H]+ and [dUrd+H]+ were found to coexist in the experiments with the 2,4-dihydroxy tautomers dominating the population. In the present study, the kinetic energy dependence of the collision-induced dissociation behavior of [Urd+H]+ and [dUrd+H]+ are examined using a guided ion beam tandem mass spectrometer to probe the mechanisms and energetics for activated dissociation of these protonated nucleosides. The primary dissociation pathways observed involve N-glycosidic bond cleavage leading to competitive elimination of protonated or neutral uracil. The potential energy surfaces (PESs) for these N-glycosidic bond cleavage pathways are mapped out via electronic structure calculations for the mixture of 2,4-dihydroxy tautomers and O4 protonated conformers of [Urd+H]+ and [dUrd+H]+ populated in the experiments. The calculated activation energies (AEs) and heats of reaction (ΔHrxns) for N-glycosidic bond cleavage at both the B3LYP and MP2(full) levels of theory are compared to the measured values. The agreement between experiment and theory indicates that B3LYP provides better estimates of the energetics of the species along the PESs for N-glycosidic bond cleavage than MP2, and that the 2,4-dihydroxy tautomers, which are stabilized by strong hydrogen-bonding interactions, predominantly influence the observed threshold dissociation behavior of [Urd+H]+ and [dUrd+H]+. [ABSTRACT FROM AUTHOR]

Our previous gas-phase infrared multiple photon dissociation action spectroscopy study of protonated 2′-deoxyadenosine and adenosine, [dAdo+H]+ and [Ado+H]+, found that both N3 and N1 protonated conformers are populated with the N3 protonated ground-state conformers predominant in the experiments. Therefore, N-glycosidic bond dissociation mechanisms of N3 and N1 protonated [dAdo+H]+ and [Ado+H]+ and the associated quantitative thermochemical values are investigated here using both experimental and theoretical approaches. Threshold collision-induced dissociation (TCID) of [dAdo+H]+ and [Ado+H]+ with Xe is studied using guided ion beam tandem mass spectrometry techniques. For both systems, N-glycosidic bond cleavage reactions are observed as the major dissociation pathways resulting in production of protonated adenine or elimination of neutral adenine. Electronic structure calculations are performed at the B3LYP/6-311+G(d,p) level of theory to probe the potential energy surfaces (PESs) for N-glycosidic bond cleavage of [dAdo+H]+ and [Ado+H]+. Relative energetics of the reactants, transition states, intermediates and products along the PESs for N-glycosidic bond cleavage are determined at the B3LYP/6-311+G(2d,2p), B3LYP-GD3BJ/6-311+G(2d,2p), and MP2(full)/6-311+G(2d,2p) levels of theory. The predicted N-glycosidic bond dissociation mechanisms for the N3 and N1 protonated species differ. Base rotation of the adenine residue enables formation of a strong N3H+…O5′ hydrogen-bonding interaction that stabilizes the N3 protonated species and its glycosidic bond. Comparison between experiment and theory indicates that the N3 protonated species determine the threshold energies, as excellent agreement between the measured and B3LYP computed activation energies (AEs) and reaction enthalpies (ΔHrxns) for N-glycosidic bond cleavage of the N3 protonated species is found. [ABSTRACT FROM AUTHOR]

Infrared multiple photon dissociation (IRMPD) action spectra of the protonated forms of 2′-deoxyguanosine-5′-monophosphate and guanosine-5′-monophosphate, [pdGuo+H]+ and [pGuo+H]+, are measured over the IR fingerprint and hydrogen-stretching regions using the FELIX free electron laser and an OPO/OPA laser system. Electronic structure calculations are performed to generate low-energy conformations of [pdGuo+H]+ and [pGuo+H]+ and determine their relative stabilities at the B3LYP/6-311+G(2d,2p)//B3LYP/6-311+G(d,p) and MP2(full)/6-311+G(2d,2p)//B3LYP/6-311+G(d,p) levels of theory. Comparative analyses of the measured IRMPD action spectra and B3LYP/6-311+G(d,p) linear IR spectra computed for the low-energy conformers are performed to determine the most favorable site of protonation and the conformers present in the experiments. These comparisons and the computed energetics find that N7 protonation is considerably preferred over O6 and N3, and the N7 protonated ground-state conformers of [pdGuo+H]+ and [pGuo+H]+ are populated in the experiments. The 2′-hydroxyl substituent does not significantly impact the stable low-energy conformers of [pdGuo+H]+vs. those of [pGuo+H]+. The effect of the 2′-hydroxyl substituent is primarily reflected in the relative intensities of the measured IRMPD bands, as the IRMPD profiles of [pdGuo+H]+ and [pGuo+H]+ are quite similar. Comparisons to previous IRMPD spectroscopy investigations of the protonated forms of the guanine nucleosides, [dGuo+H]+ and [Guo+H]+, and deprotonated forms of the guanine nucleotides, [pdGuo–H]− and [pGuo–H]−, provide insight into the effects of the phosphate moiety and protonation on the conformational features of the nucleobase and sugar moieties. Protonation is found to induce base rotation of the guanine residue to an anti orientation vs. the syn orientation found for the deprotonated forms of the guanine nucleotides. [ABSTRACT FROM AUTHOR]

The Watson–Crick structure of DNA is among the most well-known molecular structures of our time. However, alternative base-pairing motifs are also known to occur, often depending on base sequence, pH, or the presence of cations. Pairing of cytosine (C) bases induced by the sharing of a single proton (C–H+–C) may give rise to the so-called i-motif, which occurs primarily in expanded trinucleotide repeats and the telomeric region of DNA, particularly at low pH. At physiological pH, silver cations were recently found to stabilize C dimers in a C–Ag+–C structure analogous to the hemiprotonated C-dimer. Here we use infrared ion spectroscopy in combination with density functional theory calculations at the B3LYP/6-311G+(2df,2p) level to show that copper in the 1+ oxidation state induces an analogous formation of C–Cu+–C structures. In contrast to protons and these transition metal ions, alkali metal ions induce a different dimer structure, where each ligand coordinates the alkali metal ion in a bidentate fashion in which the N3 and O2 atoms of both cytosine ligands coordinate to the metal ion, sacrificing hydrogen-bonding interactions between the ligands for improved chelation of the metal cation. [ABSTRACT FROM AUTHOR]

Experimental and theoretical investigations suggest that hydrolysis of N-glycosidic bonds generally involves a concerted SN2 or a stepwise SN1 mechanism. While theoretical investigations have provided estimates for the intrinsic activation energies associated with N-glycosidic bond cleavage reactions, experimental measurements to validate the theoretical studies remain elusive. Here we report experimental investigations for N-glycosidic bond cleavage of the protonated guanine nucleosides, [dGuo+H]+ and [Guo+H]+, using threshold collision-induced dissociation (TCID) techniques. Two major dissociation pathways involving N-glycosidic bond cleavage, resulting in production of protonated guanine or the elimination of neutral guanine are observed in competition for both [dGuo+H]+ and [Guo+H]+. The detailed mechanistic pathways for the N-glycosidic bond cleavage reactions observed are mapped via electronic structure calculations. Excellent agreement between the measured and B3LYP calculated activation energies and reaction enthalpies for N-glycosidic bond cleavage of [dGuo+H]+ and [Guo+H]+ in the gas phase is found indicating that these dissociation pathways involve stepwise E1 mechanisms in analogy to the SN1 mechanisms that occur in the condensed phase. In contrast, MP2 is found to significantly overestimate the activation energies and slightly overestimate the reaction enthalpies. The 2′-hydroxyl substituent is found to stabilize the N-glycosidic bond such that [Guo+H]+ requires ∼25 kJ mol−1 more than [dGuo+H]+ to activate the glycosidic bond. [ABSTRACT FROM AUTHOR]

The gas-phase conformations of protonated uridine, [Urd+H]+, and its modified form, protonated 2′-deoxyuridine, [dUrd+H]+, generated by electrospray ionization are investigated using infrared multiple photon dissociation (IRMPD) action spectroscopy techniques. IRMPD action spectra of [Urd+H]+ and [dUrd+H]+ are measured over the IR fingerprint and hydrogen-stretching regions. [Urd+H]+ and [dUrd+H]+ exhibit very similar IRMPD spectral profiles. However, the IRMPD yields of [Urd+H]+ exceed those of [dUrd+H]+ in both the IR fingerprint and hydrogen-stretching regions. The measured spectra are compared to the linear IR spectra predicted for the stable low-energy structures of these species computed at the B3LYP/6-311+G(d,p) level of theory to determine the tautomeric conformations populated by electrospray ionization. Both B3LYP and MP2 methods find O4 and O2 protonated canonical as well as 2,4-dihydroxy tautomers among the stable low-energy structures of [Urd+H]+ and [dUrd+H]+. Comparison between the measured IRMPD and calculated linear IR spectra suggests that these species exist in their ring-closed forms and that both 2,4-dihydroxy tautomers as well as O4 protonated canonical conformers coexist in the population generated by electrospray ionization for both [Urd+H]+ and [dUrd+H]+. The 2′-deoxy modification of [dUrd+H]+ reduces the variety of 2,4-dihydroxy tautomers populated in the experiments vs. those of [Urd+H]+. [ABSTRACT FROM AUTHOR]

Binding of metal cations to the nucleobases can influence base pairing, base stacking and nucleobase tautomerism. Gas-phase condensation of dc discharge generated alkali metal cations and thermally vaporized cytosine (DC/FT) has been found to produce kinetically trapped excited tautomeric conformations of the M+(cytosine) complexes, which influences the threshold collision-induced dissociation (TCID) behavior. In order to elucidate the effects of the size of alkali metal cation on the strength of binding to the canonical form of cytosine, the binding affinities of Na+ and K+ to cytosine are re-examined here, and studies are extended to include Rb+ and Cs+ again using TCID techniques. The M+(cytosine) complexes are generated in an electrospray ionization source, which has been shown to produce ground-state tautomeric conformations of M+(cytosine). The energy-dependent cross sections are interpreted to yield bond dissociation energies (BDEs) using an analysis that includes consideration of unimolecular decay rates, the kinetic and internal energy distributions of the reactants, and multiple M+(cytosine)–Xe collisions. Revised BDEs for the Na+(cytosine) and K+(cytosine) complexes exceed those previously measured by 31.9 and 25.5 kJ mol−1, respectively, consistent with the hypothesis proposed by Yang and Rodgers that excited tautomeric conformations are accessed when the complexes are generated by DC/FT ionization. Experimentally measured BDEs are compared to theoretical values calculated at the B3LYP and MP2(full) levels of theory using the 6-311+G(2d,2p)_HW* and def2-TZVPPD basis sets. The B3LYP/def2-TZVPPD level of theory is found to provide the best agreement with the measured BDEs, suggesting that this level of theory can be employed to provide reliable energetics for similar metal–ligand systems. [ABSTRACT FROM AUTHOR]

Cisplatin, (NH 3 ) 2 PtCl 2 , has been known as a successful metal-based anticancer drug for more than half a century. Its analogue, Argplatin, arginine-linked cisplatin, (Arg)PtCl 2 , is being investigated because it exhibits reactivity towards DNA and RNA that differs from that of cisplatin. In order to understand the basis for its altered reactivity, the deprotonated and sodium cationized forms of Argplatin, [(Arg-H)PtCl 2 ] - and [(Arg)PtCl 2 + Na] + , are examined by infrared multiple photon dissociation (IRMPD) action spectroscopy in the IR fingerprint and hydrogen-stretching regions. Complementary electronic structure calculations are performed using density functional theory approaches to characterize the stable structures of these complexes and to predict their infrared spectra. Comparison of the theoretical IR spectra predicted for various stable conformations of these Argplatin complexes to their measured IRMPD spectra enables determination of the binding mode(s) of Arg to the Pt metal center to be identified. Arginine is found to bind to Pt in a bidentate fashion to the backbone amino nitrogen and carboxylate oxygen atoms in both the [(Arg-H)PtCl 2 ] - and [(Arg)PtCl 2 + Na] + complexes, the NO - binding mode. The neutral side chain of Arg also interacts with the Pt center to achieve additional stabilization in the [(Arg-H)PtCl 2 ] - complex. In contrast, Na + binds to both chlorido ligands in the [(Arg)PtCl 2 + Na] + complex and the protonated side chain of Arg is stabilized via hydrogen-bonding interactions with the carboxylate moiety. These findings are consistent with condensed-phase results, indicating that the NO - binding mode of arginine to Pt is preserved in the electrospray ionization process even under variable pH and ionic strength.

Uridine (Urd) is one of the naturally occurring pyrimidine nucleosides of RNA. 2'-Deoxyuridine (dUrd) is a naturally occurring modified form of Urd, but is not one of the canonical DNA nucleosides. In order to understand the effects of sodium cationization on the conformations and energetics of Urd and dUrd, infrared multiple photon dissociation (IRMPD) action spectroscopy experiments and density functional theory (DFT) calculations are performed. By comparing the calculated IR spectra of [Urd+Na] + and [dUrd+Na] + with the measured IRMPD spectra, the stable low-energy conformers populated in the experiments are determined. Anti oriented bidentate O2 and O2' binding conformers of [Urd+Na] + are the dominant conformers populated in the experiments, whereas syn oriented tridentate O2, O4', and O5' binding conformers of [dUrd+Na] + are dominantly populated in the experiments. The 2'-hydroxyl substituent of Urd stabilizes the anti oriented O2 binding conformers of [Urd+Na] + . Significant differences between the measured IRMPD and calculated IR spectra for complexes of [Urd+Na] + and [dUrd+Na] + involving minor tautomeric forms of the nucleobase make it obvious that none are populated in the experiments. Survival yield analyses based on energy-resolved collision-induced dissociation (ER-CID) experiments suggest that the relative stabilities of protonated and sodium cationized Urd and dUrd follow the order: [dUrd+H] + < [Urd+H] + < [dUrd+Na] + < [Urd+Na] + . The 2'-deoxy modification is found to weaken the glycosidic bond of dUrd versus that of Urd for the sodium cationized uridine nucleosides.

The Watson-Crick structure of DNA is among the most well-known molecular structures of our time. However, alternative base-pairing motifs are also known to occur, often depending on base sequence, pH, or the presence of cations. Pairing of cytosine (C) bases induced by the sharing of a single proton (C-H(+)-C) may give rise to the so-called i-motif, which occurs primarily in expanded trinucleotide repeats and the telomeric region of DNA, particularly at low pH. At physiological pH, silver cations were recently found to stabilize C dimers in a C-Ag(+)-C structure analogous to the hemiprotonated C-dimer. Here we use infrared ion spectroscopy in combination with density functional theory calculations at the B3LYP/6-311G+(2df,2p) level to show that copper in the 1+ oxidation state induces an analogous formation of C-Cu(+)-C structures. In contrast to protons and these transition metal ions, alkali metal ions induce a different dimer structure, where each ligand coordinates the alkali metal ion in a bidentate fashion in which the N3 and O2 atoms of both cytosine ligands coordinate to the metal ion, sacrificing hydrogen-bonding interactions between the ligands for improved chelation of the metal cation.

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

Threshold collision-induced dissociation techniques are employed to determine the bond dissociation energies of a wide variety of copper cation-pi complexes, Cu(+)(pi-ligand), where pi-ligand = benzene, flurobenzene, chlorobenzene, bromobenzene, iodobenzene, phenol, toluene, anisole, pyrrole, N-methylpyrrole, indole, naphthalene, aniline, N-methylaniline, and N,N-dimethylaniline. The primary and lowest energy dissociation pathway corresponds to the endothermic loss of the intact neutral pi-ligand for all complexes except those to N-methylpyrrole, indole, aniline, N-methylaniline, and N,N-dimethylaniline. In the latter complexes, the primary dissociation pathway corresponds to loss of the intact ligand accompanied by charge transfer, thereby producing a neutral copper atom and ionized pi-ligand. Fragmentation of the pi-ligands is also observed at elevated energies in several cases. Theoretical calculations at the B3LYP/6-311G(d,p) level of theory are used to determine the structures, vibrational frequencies, and rotational constants of these complexes. Multiple low-energy conformers are found for all of the copper cation-pi complexes. Theoretical bond dissociation energies are determined from single point energy calculations at the B3LYP/6-311+G(3df,2p) level of theory using the B3LYP/6-311G(d,p) optimized geometries. The agreement between theory and experiment is very good for most complexes. The nature and strength of the binding in these copper cation-pi complexes are studied and compared with the corresponding cation-pi complexes to Na(+). Natural bond orbital analyses are carried out to examine the influence of the d orbital occupation on copper cation-pi interactions.

The sequential bond dissociation energies of Cu+(imidazole)x, where x = 1-4 are determined by analysis of the kinetic energy dependence of the collision-induced dissociation with Xe in a guided ion beam tandem mass spectrometer. In all cases, the primary and lowest energy dissociation channel observed is the endothermic loss of an intact imidazole molecule. The primary cross section thresholds are interpreted to yield 0 K and 298 K bond dissociation energies after accounting for the effects of multiple ion-neutral collisions, kinetic and internal energy distributions of the reactants, and dissociation lifetimes. To obtain model structures, vibrational frequencies, rotational constants and energetics for the Cu+(imidazole)x complexes and their dissociation products, density functional theory calculations at the B3LYP/6-31G* level are performed. Theoretical bond dissociation energies are determined from single point energy calculations at the B3LYP/6-311+G(2d,2p) level of theory using the B3LYP/6-31G* optimized geometries. Excellent agreement between theory and experiment is observed for the Cu+(imidazole)x complexes, where x = 1, 2 and 4. In contrast, theory systematically underestimates the strength of the binding in the Cu+(imidazole)3 complex. The ground state structures of the Cu+(imidazole), complexes and the trends in the sequential bond dissociation energies are explained in terms of stabilization gained from sd hybridization and hydrogen bonding interactions and destabilization arising from ligand-ligand repulsion. The trends in the binding of these complexes are also examined to provide insight into the structural and functional roles that histidine and other ligands play in the behavior of metalloproteins and metalloenzymes.