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1. The intrinsic basicity of the phosphate backbone exceeds that of uracil and thymine residues: protonation of the phosphate moiety is preferred over the nucleobase for pdThd and pUrd

   https://doi.org/10.1039/C7CP05521H  

   Wu, R. R.; Hamlow, L. A.; He, C. C.; Nei, Y.-w.; Berden, G.; Oomens, J.; Rodgers, M. T. (January 2017, Physical Chemistry Chemical Physics)

   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. 

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2. Infrared multiple photon dissociation action spectroscopy of protonated glycine, histidine, lysine, and arginine complexed with 18-crown-6 ether

   https://doi.org/10.1039/c9cp02265a  

   McNary, Christopher P.; Nei, Y.-W.; Maitre, Philippe; Rodgers, M. T.; Armentrout, P. B. (June 2019, Physical Chemistry Chemical Physics)

   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. 

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3. Experimental and theoretical investigations of infrared multiple photon dissociation spectra of arginine complexes with Zn ²⁺ and Cd ²⁺

   https://doi.org/10.1039/c8cp03484b  

   Chalifoux, Aaron M.; Boles, Georgia C.; Berden, Giel; Oomens, Jos; Armentrout, P. B. (January 2018, Physical Chemistry Chemical Physics)

   Arginine (Arg) complexes with Zn 2+ and Cd 2+ were examined by infrared multiple photon dissociation (IRMPD) action spectroscopy using light from a free electron laser. Electrospray ionization generated complexes of deprotonated Arg with Zn 2+ , [Zn(Arg–H)] + , and Arg with CdCl + , CdCl + (Arg). Possible low-energy conformers of these species were found using quantum chemical calculations, and their calculated IR spectra were compared to experimentally measured IRMPD spectra. Calculations were performed at the B3LYP/6-311+G(d,p) level for Zn 2+ complexes and B3LYP/def2-TZVP with an SDD effective core potential on cadmium for CdCl + complexes. [Zn(Arg–H)] + was found to adopt a charge-solvated, tridentate [N,CO − ,N ω ′] structure where Zn 2+ binds to the backbone amine, carbonyl oxygen, and side-chain terminal guanidine nitrogen (N ω ′). The CdCl + (Arg) species was suggested to be a mixture of a dominant (∼85%) charge-solvated, tridentate [N,CO,N ω ′] structure where the CdCl + binds to the backbone amine, carbonyl, and side-chain imine (N ω ′) and a minor (∼15%) bidentate [N,CO − ](N ω ′H 2 + ) zwitterionic structure where the metal center binds to the backbone amine and carbonyl oxygen with intramolecular proton migration from the hydroxyl to the N ω ′ guanidine nitrogen (as designated in parenthesis). 

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4. Structural determination of arginine-linked cisplatin complexes via IRMPD action spectroscopy: arginine binds to platinum via NO ⁻ binding mode

   https://doi.org/10.1039/d1cp03407c  

   He, C. C.; Hamlow, L. A.; Kimutai, B.; Roy, H. A.; Devereaux, Zachary J.; Cunningham, N. A.; Martens, J.; Berden, G.; Oomens, J.; Chow, C. S.; et al (October 2021, Physical Chemistry Chemical Physics)

   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. 

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5. Is non-statistical dissociation a general feature of guanine–cytosine base-pair ions? Collision-induced dissociation of a protonated 9-methylguanine–1-methylcytosine Watson–Crick base pair, and comparison with its deprotonated and radical cation analogues

   https://doi.org/10.1039/d0cp04243a  

   Sun, Yan; Moe, May Myat; Liu, Jianbo (November 2020, Physical Chemistry Chemical Physics)

   null (Ed.)

   A guided-ion beam tandem mass spectrometric study was performed on collision-induced dissociation (CID) of a protonated 9-methylguanine–1-methylcytosine Watson–Crick base pair (designated as WC-[9MG·1MC + H] + ), from which dissociation pathways and dissociation energies were determined. Electronic structure calculations at the DFT, RI-MP2 and DLPNO-CCSD(T) levels of theory were used to identify product structures and delineate reaction mechanisms. Intra-base-pair proton transfer (PT) of WC-[9MG·1MC + H] + results in conventional base-pair conformations that consist of hydrogen-bonded [9MG + H] + and 1MC and proton-transferred conformations that are formed by PT from the N1 of [9MG + H] + to the N3′ of 1MC. Two types of conformers were distinguished by CID in which the conventional conformers produced [9MG + H] + product ions whereas the proton-transferred conformers produced [1MC + H] + . The conventional conformers have a higher population (99.8%) and lower dissociation energy than the proton-transferred counterparts. However, in contrast to what was expected from the statistical dissociation of the equilibrium base-pair conformational ensemble, the CID product ions of WC-[9MG·1MC + H] + were dominated by [1MC + H] + rather than [9MG + H] + . This finding, alongside the non-statistical CID reported for deprotonated guanine–cytosine (Lu et al. ; PCCP , 2016, 18 , 32222) and guanine–cytosine radical cation (Sun et al. ; PCCP , 2020, 22 , 14875), reinforces that non-statistical dissociation is a distinctive feature of singly-charged Watson–Crick guanine–cytosine base pairs. It implies that intra-base-pair PT facilitates the formation of proton-transferred conformers in these systems and the ensuing conformers have loose transition states for dissociation. The monohydrate of WC-[9MG·1MC + H] + preserves non-statistical CID kinetics and introduces collision-induced methanol elimination via the reaction of the water ligand with a methyl group. 

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