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Comparison between the gas-phase fragmentation of odd-electron [M.sup.+]*, [[M + H].sup.2+]*, and [[M - 2H].sup.-]* ions of model peptides suggests that charge-remote radical-driven fragmentation pathways play an important role in the dissociation of odd-electron peptide ions. We have found that charge-remote processes are responsible for a variety of side-chain losses from the precursor ion and some backbone fragmentation. These fragmentation pathways most likely involve hydrogen abstraction by the radical site that initiates subsequent cleavages. These findings are generally relevant to our understanding of the fragmentation patterns of odd-electron peptide ions produced through various approaches including the capture of low-energy electrons, electron detachment, and electron transfer.

The kinetic energy dependence of the collision-induced dissocistion of M(super +)(imidazole), where M(super +) = Na(super +), Mg(super +), AI(super +), Ca(super +), Sc(super+), Ti(super +), V(super +), Cr(super +), Mn(super +), Fe(super +), Co(super +), Ni(super +), Cu(super +), and Zn(super +), with Xe are examined in a guided ion beam mass spectrometer are presented. The dominant dissociation process in most cases is loss of the intact imidazole ligand, although the Sc(super +), Ti(super +), and V(super +) complexes show activated dissociation processes that compete with this channel.

The gas phase reactivity of 1,3,5-triazine with several oxyanions and carbanions, as well as amide, was evaluated using a flowing afterglow-selected ion flow tube mass spectrometer. Isotopic labeling, H/D exchange, and collision induced dissociation experiments were conducted to facilitate the interpretation of structures and fragmentation processes. A multi-step (→ HCN + HCN → CN + 2 HCN) and/or single-step (→ CN + 2 HCN) ring-opening collision-induced fragmentation process appears to exist for 1,3,5-triazinide. In addition to proton and hydride transfer reactions, the data indicate a competitive nucleophilic aromatic addition pathway (SAr) over a wide range of relative gas phase acidities to form strong anionic σ-adducts (Meisenheimer complexes). The significant hydride acceptor properties and stability of the anionic σ-adducts are rationalized by extremely electrophilic carbon centers and symmetric charge delocalization at the electron-withdrawing nitrogen positions. The types of anion-arene binding motifs and their influence on reaction pathways are discussed. [ABSTRACT FROM AUTHOR]

Fragmentation pathways of peptide radical cations, M+·, with well-defined initial location of the radical site were explored using collision-induced dissociation (CID) experiments. Peptide radical cations were produced by gas-phase fragmentation of CoIII(salen)–peptide complexes [salen = N,N''-ethylenebis (salicylideneiminato)]. Subsequent hydrogen abstraction from the β-carbon of the side-chain followed by Cα–Cβ bond cleavage results in the loss of a neutral side chain and formation of an α-radical cation with the radical site localized on the α-carbon of the backbone. Similar CID spectra dominated by radical-driven dissociation products were obtained for a number of arginine-containing α-radicals, suggesting that for these systems radical migration precedes fragmentation. In contrast, proton-driven fragmentation dominates CID spectra of α-radicals produced via the loss of the arginine side chain. Radical-driven fragmentation of large M+· peptide radical cations is dominated by side-chain losses, formation of even-electron a-ions and odd-electron x-ions resulting from Cα–C bond cleavages, formation of odd-electron z-ions, and loss of the N-terminal residue. In contrast, charge-driven fragmentation produces even-electron y-ions and odd-electron b-ions. [Copyright &y& Elsevier]

Time- and collision energy-resolved surface-induced dissociation (SID) of ternary complexes of CoIII(salen)+, FeIII(salen)+, and MnIII(salen)+ with several angiotensin peptide analogues was studied using a Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS) specially equipped to perform SID experiments. Time-resolved fragmentation efficiency curves (TFECs) were modeled using an RRKM-based approach developed in our laboratory. The approach utilizes a very flexible analytical expression for the internal energy deposition function that is capable of reproducing both single-collision and multiple-collision activation in the gas phase and excitation by collisions with a surface. The energetics and dynamics of competing dissociation pathways obtained from the modeling provides important insight on the competition between proton transfer, electron transfer, loss of neutral peptide ligand, and other processes that determine gas-phase fragmentation of these model systems. Similar fragmentation behavior was obtained for various CoIII(salen)-peptide systems of different angiotensin analogues. In contrast, dissociation pathways and relative stabilities of the complexes changed dramatically when cobalt was replaced with trivalent iron or manganese. We demonstrate that the electron-transfer efficiency is correlated with redox properties of the metalIII(salen) complexes (Co > Fe > Mn), while differences in the types of fragments formed from the complexes reflect differences in the modes of binding between the metal-salen complex and the peptide ligand. RRKM modeling of time- and collision-energy-resolved SID data suggests that the competition between proton transfer and electron transfer during dissociation of CoIII(salen)-peptide complexes is mainly determined by differences in entropy effects while the energetics of these two pathways are very similar. [ABSTRACT FROM AUTHOR]

The influence of halogenation on the properties of uracil and its noncovalent interactions with alkali metal ions is investigated both experimentally and theoretically. Bond dissociation energies of alkali metal ion--halouracil complexes, M+(XU), are determined using threshold collision-induced dissociation techniques in a guided ion beam mass spectrometer,where M+ = Li+, Na+ and K+ and XU = 5-fluorouracil, 5-chlorouracil, 6-chlorouracil, 5-bromouracil, and 5-iodouracil. The structures and theoretical bond dissociation energies of these complexes are determined from ab initio calculations. Theoretical calculations are also performed to examine the influence of halogenation on the acidities, proton affinities, and Watson--Crick base pairing energies. Halogenation of uracil is found to produce a decrease in the proton affinity, an increase in the alkali metal ion binding affinities, an increase in the acidity, and stabilization of the A::U base pair. In addition, alkali metal ion binding is expected to lead to an increase in the stability of nucleic acids by reducing the charge on the nucleic acid in a zwitterion effect as well as through additional noncovalent interactions between the alkali metal ion and the nucleobases. [ABSTRACT FROM AUTHOR]

Ambient mass spectrometry imaging (MSI) is an emerging field with great potential for the detailed spatial analysis of biological samples with minimal pretreatment. We have developed a miniaturized sampling and ionization device, the Single-probe, which uses in-situ surface micro-extraction to achieve high detection sensitivity and spatial resolution during MSI experiments. The Single-probe was coupled to a Thermo LTQ Orbitrap XL mass spectrometer and was able to create high spatial and high mass resolution MS images at 8 ± 2 and 8.5 μm on flat polycarbonate microscope slides and mouse kidney sections, respectively, which are among the highest resolutions available for ambient MSI techniques. Our proof-of-principle experiments indicate that the Single-probe MSI technique has the potential to obtain ambient MS images with very high spatial resolutions with minimal sample preparation, which opens the possibility for subcellular ambient tissue MSI to be performed in the future. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

We have used the Single-probe, a miniaturized sampling device utilizing in-situ surface microextraction for ambient mass spectrometry (MS) analysis, for the high resolution MS imaging (MSI) of negatively charged species in the positive ionization mode. Two dicationic compounds, 1,5-pentanediyl-bis(1-butylpyrrolidinium) difluoride [C(bpyr)F] and 1,3-propanediyl-bis(tripropylphosphonium) difluoride [C(triprp)F], were added into the sampling solvent to form 1+ charged adducts with the negatively charged species extracted from tissues. We were able to detect 526 and 322 negatively charged species this way using [C(bpyr)F] and [C(triprp)F], respectively, including oleic acid, arachidonic acid, and several species of phosphatidic acid, phosphoethanolamine, phosphatidylserine, phosphatidylglycerol, phosphatidylinositol, and others. In conjunction with the identification of the non-adduct cations, we have tentatively identified a total number of 1200 and 828 metabolites from mouse brain sections using [C(bpyr)F] and [C(triprp)F], respectively, through high mass accuracy measurements (mass error <5 ppm); MS/MS analyses were also performed to verify the identity of selected species. In addition to the high mass accuracy measurement, we were able to generate high spatial resolution (~17 μm) MS images of mouse brain sections. Our study demonstrated that utilization of dicationic compounds in the surface microextraction with the Single-probe device can perform high mass and spatial resolution ambient MSI measurements of broader types of compounds in tissues. Other reagents can be potentially used with the Single-probe device for a variety of reactive MSI studies to enable the analysis of species that are previously intractable. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Although most advanced-stage ovarian cancers initially respond to platinum- and taxane-based chemotherapy, the majority of them will recur and eventually develop chemoresistance. Among all drug resistance mechanisms, reduced drug uptake in tumors is regarded as an important pathway acquired by drug-resistant cancer cells. For patients with ovarian cancer, chemoresistant cells can develop into multicellular spheroids and spread through ascite fluid that accumulates in their abdomen. These spheroids consist of 3D structures that are highly heterogeneous with different shapes, sizes, and compositions of cell types. Thus, studying drug uptake at the single spheroid level is important for understanding chemosensitivity and chemoresistance; however, drug-uptake studies in single spheroids have not been previously reported due to the lack of a suitable analytical technique. In this study, we cultured spheroids using the ovarian cancer cell line (OVCAR-8) and treated them using paclitaxel or OSW-1, a natural compound with anticancer properties. We then developed a method of quantifying drug uptake in single spheroids using LC/MS measurements and then normalized the drug amount in each spheroid to its size and total protein content. Our method can be used in translational studies of drug development, treatment, and prediction of drug efficacy prior to chemotherapy., Competing Interests: The authors declare no competing financial interest., (© 2024 American Chemical Society.)

Mung bean contains up to 32.6% protein and is one of the great sources of plant-based protein. Because many allergens also function as defense-related proteins, it is important to determine their abundance levels in the high-yielding, disease-resistant cultivars. In this study, for the first time, we compared the seed proteome of high-yielding mung bean cultivars developed by a conventional breeding approach. Using a label-free quantitative proteomic platform, we successfully identified and quantified a total of 1373 proteins. Comparative analysis between the high-yielding disease-resistant cultivar (MC5) and the other three cultivars showed that a total of 69 common proteins were significantly altered in their abundances across all cultivars. Bioinformatic analysis of these altered proteins demonstrated that PDF1 (a defensin-like protein) exhibited high sequence similarity and epitope matching with the established peanut allergens, indicating a potential mung bean allergen that showed a cultivar-specific response. Conversely, known mung bean allergen proteins such as PR-2/PR-10 (Vig r 1), Vig r 2, Vig r 4, LTP1, β-conglycinin, and glycinin G4 showed no alternation in the MC5 compared to other cultivars. Taken together, our findings suggest that the known allergen profiles may not be impacted by the conventional plant breeding method to develop improved mung bean cultivars.

The growth of all-inorganic perovskite single-crystal microstructures on substrates is a promising approach for constructing photonic and electronic microdevices. However, current preparation methods typically involve direct control of ions or atoms, which often depends on specific lattice-matched substrates for epitaxial growth and other stringent conditions that limit the mild preparation and flexibility of device integration. Herein, we present the on-substrate fabrication of CsPbBr 3 single-crystal microstructures obtained via a nanoparticle self-assembly assisted low-temperature sintering (NSALS) method. Sintering guided by self-assembled atomically oriented superlattice embryos facilitated the formation of single-crystal microstructures under mild conditions without substrate dependence. The as-prepared on-substrate microstructures exhibited a consistent out-of-plane orientation with a carrier lifetime of up to 82.7 ns. Photodetectors fabricated by using these microstructures exhibited an excellent photoresponse of 9.15 A/W, and the dynamic optical response had a relative standard deviation as low as 0.1831%. The discrete photosensor microarray chip with 174000 pixels in a 100 mm 2 area showed a response difference of less than 6%. This method of nanoscale particle-controlled single crystal growth on a substrate offers a perspective for mild-condition preparation and in situ repair of crystals of various types. This advancement can propel the flexible integration and widespread application of perovskite devices.

Extracellular compounds in tumors play critical roles in intercellular communication, tumor proliferation, and cancer cell metastasis. However, the lack of appropriate techniques leads to limited studies of extracellular metabolite. Here, we introduced a microscale collection device, the Micro-funnel, fabricated from biocompatible fused silica capillary. With a small probe size (∼25 μm), the Micro-funnel can be implanted into live multicellular tumor spheroids to accumulate the extracellular metabolites produced by cancer cells. Metabolites collected in the Micro-funnel device were then extracted by a microscale sampling and ionization device, the Single-probe, for real-time mass spectrometry (MS) analysis. We successfully detected the abundance change of anticancer drug irinotecan and its metabolites inside spheroids treated under a series of conditions. Moreover, we found that irinotecan treatment dramatically altered the composition of extracellular compounds. Specifically, we observed the increased abundances of a large number of lipids, which are potentially related to the drug resistance of cancer cells. This study provides a novel way to detect the extracellular compounds inside live spheroids, and the successful development of our technique can benefit the research in multiple areas, including the microenvironment inside live tissues, cell-cell communication, biomarker discovery, and drug development.

A unique mass spectrometry (MS) method has been developed to determine the negatively charged species in live single cells using the positive ionization mode. The method utilizes dicationic ion-pairing compounds through the miniaturized multifunctional device, the single-probe, for reactive MS analysis of live single cells under ambient conditions. In this study, two dicationic reagents, 1,5-pentanediyl-bis(1-butylpyrrolidinium) difluoride (C5(bpyr)2F2) and 1,3-propanediyl-bis(tripropylphosphonium) difluoride (C3(triprp)2F2), were added in the solvent and introduced into single cells to extract cellular contents for real-time MS analysis. The negatively charged (1- charged) cell metabolites, which form stable ion-pairs (1+ charged) with dicationic compounds (2+ charged), were detected in positive ionization mode with a greatly improved sensitivity. We have tentatively assigned 192 and 70 negatively charged common metabolites as adducts with (C5(bpyr)2F2) and (C3(triprp)2F2), respectively, in three separate SCMS experiments in the positive ion mode. The total number of tentatively assigned metabolites is 285 for C5(bpyr)2F2 and 143 for C3(triprp)2F2. In addition, the selectivity of dicationic compounds in the complex formation allows for the discrimination of overlapped ion peaks with low abundances. Tandem (MS/MS) analyses at the single cell level were conducted for selected adduct ions for molecular identification. The utilization of the dicationic compounds in the single-probe MS technique provides an effective approach to the detection of a broad range of metabolites at the single cell level.

Dicyanamide [N(CN)2(-)] is a common anionic component of ionic liquids, several of which have shown hypergolic reactivity upon mixing with white-fuming nitric acid. In this study, we explore the thermochemistry of dicyanamide and its reactivity with nitric acid and other molecules to gain insight into the initial stages of the hypergolic phenomenon. We have developed and utilized an electrospray ion source for our selected ion flow tube (SIFT) to generate the dicyanamide anion. We have explored the general reactivity of this ion with several neutral molecules and atoms. Dicyanamide does not show reactivity with O2, H2SO4, H2O2, DBr, HCl, NH3, N2O, SO2, COS, CO2, CH3OH, H2O, CH4, N2, CF4, or SF6 (k < 1 × 10(-12) cm(3)/s); moreover, dicyanamide does not react with N atom, O atom, or electronically excited molecular oxygen (k < 5 × 10(-12) cm(3)/s), and our previous studies showed no reactivity with H atom. However, at 0.45 Torr helium, we observe the adduct of dicyanamide with nitric acid with an effective bimolecular rate constant of 2.7 × 10(-10) cm(3)/s. Intrinsically, dicyanamide is a very stable anion in the gas phase, as illustrated by its lack of reactivity, high electron-binding energy, and low proton affinity. The lack of reactivity of dicyanamide with H2SO4 gives an upper limit for the gas-phase deprotonation enthalpy of the parent compound (HNCNCN; <310 ± 3 kcal/mol). This limit is in agreement with theoretical calculations at the MP2/6-311++G(d,p) level of theory, finding that ΔH298 K(HNCNCN) = 308.5 kcal/mol. Dicyanamide has two different proton acceptor sites. Experimental and computational results indicate that it is lower in energy to protonate the terminal nitrile nitrogen than the central nitrogen. Although proton transfer to dicyanamide was not observed for any of the acidic molecules investigated here, the calculations on dicyanamide with one to three nitric acid molecules reveal that higher-order solvation can favor exothermic proton transfer. Furthermore, the formation of 1,5-dinitrobiuret, proposed to be the key intermediate during the hypergolic ignition of dicyanamide ionic liquids with nitric acid, is investigated by calculation of the reaction coordinate. Our results suggest that solvation dynamics of dicyanamide with nitric acid play an important role in hypergolic ignition and the interactions at the droplet/condensed-phase surface between the two hypergolic liquids are very important. Moreover, dicyanamide exists in the atmosphere of Saturn's moon, Titan; the intrinsic stability of dicyanamide strongly suggests that it may exist in molecular clouds of the interstellar medium, especially in regions where other stable carbon-nitrogen anions have been detected.

Germanium is a highly promising anode material for lithium-ion batteries as a consequence of its large theoretical specific capacity, good electrical conductivity, and fast lithium ion diffusivity. In this work, Co3O4 nanowire array fabricated on nickel foam was designed as a nanostructured current collector for Ge anode. By limiting the voltage cutoff window in an appropriate range, the obtained Ge anode exhibits excellent lithium storage performance in half- and full-cells, which can be mainly attributed to the designed nanostructured current collector with good conductivity, enough buffering space for the volume change, and shortened ionic transport length. More importantly, the assembled Ge/LiCoO2 full-cell shows a high energy density of 475 Wh/kg and a high power density of 6587 W/kg. A high capacity of 1184 mA h g(-1) for Ge anode was maintained at a current density of 5000 mA g(-1) after 150 cycles.

We have developed a new mass spectrometry (MS) technology, the Single-probe MS, capable of real-time, in situ metabolomic analysis of individual living cells. The Single-probe is a miniaturized multifunctional sampling and ionization device that is directly coupled to the mass spectrometer. With a sampling tip smaller than individual eukaryotic cells (<10 μm), the Single-probe can be inserted into single cells to sample the intracellular compounds for real-time MS analysis. We have used the Single-probe to detect several cellular metabolites and the anticancer small molecules paclitaxel, doxorubicin, and OSW-1 in individual cervical cancer cells (HeLa). Single cell mass spectrometry (SCMS) is an emerging scientific technology that could reshape the analytical science of many research disciplines, and the Single-probe MS technology is a novel method for SCMS that, through its accessible fabrication protocols, can be broadly applied to different research areas.

The effect of the basic residue on the energetics, dynamics, and mechanisms of backbone fragmentation of protonated peptides was investigated. Time-resolved and collision energy-resolved surface-induced dissociation (SID) of singly protonated peptides with the N-terminal arginine residue and their analogues, in which arginine is replaced with less basic lysine and histidine residues, was examined using a specially configured Fourier transform ion cyclotron resonance mass spectrometer (FTICR-MS). SID experiments demonstrated different kinetics of formation of several primary product ions of peptides with and without arginine residue. The energetics and dynamics of these pathways were determined from Rice-Ramsperger-Kassel-Marcus (RRKM) modeling of the experimental data. Comparison between the kinetics and energetics of fragmentation of arginine-containing peptides and the corresponding methyl ester derivatives provides important information on the effect of dissociation pathways involving salt bridge (SB) intermediates on the observed fragmentation behavior. Because pathways involving SB intermediates are characterized by low threshold energies, they efficiently compete with classical oxazolone and imine/enol pathways of arginine-containing peptides on a long time scale of the FTICR instrument. In contrast, fragmentation of histidine- and lysine-containing peptides is largely determined by canonical pathways. Because SB pathways are characterized by negative activation entropies, fragmentation of arginine-containing peptides is kinetically hindered and observed at higher collision energies as compared to their lysine- and histidine-containing analogues.

Molecular anions have been recently detected in the denser regions of the interstellar medium. However, the chemical reactions of molecular anions with atomic species that are abundant in the ISM remain largely unexplored. This work is an experimental and computational study of CH(2)CN(-), CH(3)CHCN(-), (CH(3))(2)CCN(-), and CH(2)CHO(-) reacting with N and O atoms. In all cases the reactions of anions with O atoms exhibit larger reaction rate constants compared to the corresponding reactions with N atoms. Our study indicates that spin-forbidden reactions are the probable pathways in the reactions with N atoms, whereas spin-allowed reactions are the dominant processes in the reactions with O atoms. The major factor influencing the reaction rate constants of anions with N and O atoms is whether a spin-allowed barrierless pathway exists. The rich chemistry observed in this work provides a greater understanding of the ion-atom reaction processes, as well as some new avenues for further spin chemistry research.

Fragmentation of protonated RVYIHPF and RVYIHPF-OMe and the corresponding radical cations was studied using time- and collision energy-resolved surface-induced dissociation (SID) in a Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS) specially equipped to perform SID experiments. Peptide radical cations were produced by gas-phase fragmentation of Co (III)(salen)-peptide complexes. Both the energetics and the mechanisms of dissociation of even-electron and odd-electron angiotensin III ions are quite different. Protonated molecules are much more stable toward fragmentation than the corresponding radical cations. RRKM modeling of the experimental data suggests that this stability is largely attributed to differences in threshold energies for dissociation, while activation entropies are very similar. Detailed analysis of the experimental data obtained for radical cations demonstrated the presence of two distinct structures separated by a high free-energy barrier. The two families of structures were ascribed to the canonical and zwitterionic forms of the radical cations produced in our experiments.

Surface-induced dissociation (SID) of the singly protonated complex of vancomycin antibiotic with cell wall peptide analogue (N(alpha),N(epsilon)-diacetyl-L-Lys-D-Ala-D-Ala) was studied using a 6 T Fourier Transform Ion Cyclotron Resonance Mass Spectrometer (FT-ICR MS) specially configured for SID experiments. The binding energy between the vancomycin and the peptide was obtained from the RRKM modeling of the time- and energy-resolved fragmentation efficiency curves (TFECs) of the precursor ion and its fragments. Molecular dynamics simulations of the vancomycin, peptide, and vancomycin-peptide complex were carried out to explore the low energy conformations. Density functional theory (DFT) calculations of the geometries, proton affinities, and binding energies were performed for several model systems including vancomycin (V), vancomycin aglycon (VA), N(alpha),N(epsilon)-diacetyl-L-Lys-D-Ala-D-Ala, and noncovalent complexes of VA with N-acetyl-D-Ala-D-Ala and V with N(alpha),N(epsilon)-diacetyl-L-Lys-D-Ala-D-Ala. Comparison between the experimental and computational results suggests that the most probable structure of the complex observed in our experiments corresponds to the neutral peptide bound to the vancomycin protonated at the primary amine of the disaccharide group. The experimental binding energy of 30.9 +/- 1.8 kcal/mol is in good agreement with the binding energy of 36.3-42.0 kcal/mol calculated for the model system representing the preferred structure of the complex.

Time- and collision energy-resolved surface-induced dissociation (SID) of ternary complexes of Co(III)(salen)+, Fe(III)(salen)+, and Mn(III)(salen)+ with several angiotensin peptide analogues was studied using a Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS) specially equipped to perform SID experiments. Time-resolved fragmentation efficiency curves (TFECs) were modeled using an RRKM-based approach developed in our laboratory. The approach utilizes a very flexible analytical expression for the internal energy deposition function that is capable of reproducing both single-collision and multiple-collision activation in the gas phase and excitation by collisions with a surface. The energetics and dynamics of competing dissociation pathways obtained from the modeling provides important insight on the competition between proton transfer, electron transfer, loss of neutral peptide ligand, and other processes that determine gas-phase fragmentation of these model systems. Similar fragmentation behavior was obtained for various Co(III)(salen)-peptide systems of different angiotensin analogues. In contrast, dissociation pathways and relative stabilities of the complexes changed dramatically when cobalt was replaced with trivalent iron or manganese. We demonstrate that the electron-transfer efficiency is correlated with redox properties of the metal(III)(salen) complexes (Co > Fe > Mn), while differences in the types of fragments formed from the complexes reflect differences in the modes of binding between the metal-salen complex and the peptide ligand. RRKM modeling of time- and collision-energy-resolved SID data suggests that the competition between proton transfer and electron transfer during dissociation of Co(III)(salen)-peptide complexes is mainly determined by differences in entropy effects while the energetics of these two pathways are very similar.

Experimental and theoretical studies are carried out to determine the influence of thioketo substitution on the properties of uracil and its noncovalent interactions with alkali metal ions. Bond dissociation energies of alkali metal ion-thiouracil complexes, M(+)(SU), are determined using threshold collision-induced dissociation techniques in a guided ion beam mass spectrometer, where M(+) = Li(+), Na(+), and K(+) and SU = 2-thiouracil, 4-thiouracil, 2,4-dithiouracil, 5-methyl-2-thiouracil, and 6-methyl-2-thiouracil. Ab initio electronic structure calculations are performed to determine the structures and theoretical bond dissociation energies of these complexes and provide molecular constants necessary for thermodynamic analysis of the experimental data. Theoretical calculations are also performed to examine the influence of thioketo substitution on the acidities, proton affinities, and A::SU Watson-Crick base pairing energies. In general, thioketo substitution leads to an increase in both the proton affinity and the acidity of uracil. 2-Thio substitution generally results in an increase in the alkali metal ion binding affinities but has almost no affect on the stability of the A::SU base pair. In contrast, 4-thio substitution results in a decrease in the alkali metal ion binding affinities and a significant decrease in the stability of the A::SU base pair. In addition, alkali metal ion binding is expected to lead to an increase in the stability of both single-stranded and double-stranded nucleic acids by reducing the charge on the nucleic acid in a zwitterion effect as well as through additional noncovalent interactions between the alkali metal ion and the nucleobases.

Threshold collision-induced dissociation techniques are employed to determine bond dissociation energies (BDEs) of mono- and bis-complexes of alkali metal cations, Li+, Na+, K+, Rb+, and Cs+, with indole, C8H7N. The primary and lowest energy dissociation pathway in all cases is endothermic loss of an intact indole ligand. Sequential loss of a second indole ligand is observed at elevated energies for the bis-complexes. Density functional theory calculations at the B3LYP/6-31G level of theory are used to determine the structures, vibrational frequencies, and rotational constants of these complexes. Theoretical BDEs are determined from single point energy calculations at the MP2(full)/6-311+G(2d,2p) level using the B3LYP/6-31G* geometries. The agreement between theory and experiment is very good for all complexes except Li+ (C8H7N), where theory underestimates the strength of the binding. The trends in the BDEs of these alkali metal cation-indole complexes are compared with the analogous benzene and naphthalene complexes to examine the influence of the extended pi network and heteroatom on the strength of the cation-pi interaction. The Na+ and K+ binding affinities of benzene, phenol, and indole are also compared to those of the aromatic amino acids, phenylalanine, tyrosine, and tryptophan to elucidate the factors that contribute to the binding in complexes to the aromatic amino acids. The nature of the binding and trends in the BDEs of cation-pi complexes between alkali metal cations and benzene, phenol, and indole are examined to help understand nature's preference for engaging tryptophan over phenylalanine and tyrosine in cation-pi interactions in biological systems.