Liquid-jet photoemission spectroscopy (LJ-PES) allows for a direct probing of electronic structure in aqueous solutions. We show the applicability of the approach to biomolecules in a complex environment, exploring site-specific information on the interaction of adenosine triphosphate in the aqueous phase (ATP(aq)) with magnesium (Mg2+(aq)), highlighting the synergy brought about by the simultaneous analysis of different regions in the photoelectron spectrum. In particular, we demonstrate intermolecular Coulombic decay (ICD) spectroscopy as a new and powerful addition to the arsenal of techniques for biomolecular structure investigation. We apply LJ-PES assisted by electronic-structure calculations to study ATP(aq) solutions with and without dissolved Mg2+. Valence photoelectron data reveal spectral changes in the phosphate and adenine features of ATP(aq) due to interactions with the divalent cation. Chemical shifts in Mg 2p, Mg 2s, P 2p, and P 2s core-level spectra as a function of the Mg2+/ATP concentration ratio are correlated to the formation of [Mg(ATP) 2]6-(aq), [MgATP]2-(aq), and [Mg2ATP](aq) complexes, demonstrating the element sensitivity of the technique to Mg2+-phosphate interactions. The most direct probe of the intermolecular interactions between ATP(aq) and Mg2+(aq) is delivered by the emerging ICD electrons following ionization of Mg 1s electrons. ICD spectra are shown to sensitively probe ligand exchange in the Mg2+-ATP(aq) coordination environment. In addition, we report and compare P 2s data from ATP(aq) and adenosine mono- and diphosphate (AMP(aq) and ADP(aq), respectively) solutions, probing the electronic structure of the phosphate chain and the local environment of individual phosphate units in ATP(aq). Our results provide a comprehensive view of the electronic structure of ATP(aq) and Mg2+-ATP(aq) complexes relevant to phosphorylation and dephosphorylation reactions that are central to bioenergetics in living organisms.

Chemical Sciences Division Lawrence Berkeley National Laboratory Berkeley California 94720 United States

Department of Chemistry University of California Berkeley California 94720 United States

Department of Chemistry University of Southern California Los Angeles California 90089 United States

Department of Physical Chemistry University of Chemistry and Technology Prague Technická 5 Prague 6 16628 Czech Republic

Fritz Haber Institut der Max Planck Gesellschaft Faradayweg 4 6 14195 Berlin Germany

Institut für Kernphysik Goethe Universität Frankfurt Max von Laue Straße 1 60438 Frankfurt am Main Germany

Zobrazit více v PubMed

Reinert F.; Hüfner S. Photoemission spectroscopy—from early days to recent applications. New J. Phys. 2005, 7, 97.10.1088/1367-2630/7/1/097. DOI

Faubel M.; Schlemmer S.; Toennies J. P. A molecular beam study of the evaporation of water from a liquid jet. Z. Phys. D 1988, 10 (2−3), 269–277. 10.1007/BF01384861. DOI

Thürmer S.; et al. Accurate vertical ionization energy and work function determinations of liquid water and aqueous solutions. Chem. Sci. 2021, 12 (31), 10558–10582. 10.1039/D1SC01908B. PubMed DOI PMC

Winter B.; et al. Full Valence Band Photoemission from Liquid Water Using EUV Synchrotron Radiation. J. Phys. Chem. A 2004, 108 (14), 2625–2632. 10.1021/jp030263q. DOI

Mudryk K. D.; et al. The electronic structure of the aqueous permanganate ion: aqueous-phase energetics and molecular bonding studied using liquid jet photoelectron spectroscopy. Phys. Chem. Chem. Phys. 2020, 22 (36), 20311–20330. 10.1039/D0CP04033A. PubMed DOI

Pluhařová E.; et al. Transforming Anion Instability into Stability: Contrasting Photoionization of Three Protonation Forms of the Phosphate Ion upon Moving into Water. J. Phys. Chem. B 2012, 116 (44), 13254–13264. 10.1021/jp306348b. PubMed DOI

Malerz S.; et al. Following in Emil Fischer’s Footsteps: A Site-Selective Probe of Glucose Acid–Base Chemistry. J. Phys. Chem. A 2021, 125 (32), 6881–6892. 10.1021/acs.jpca.1c04695. PubMed DOI PMC

Schroeder C. A.; et al. Oxidation Half-Reaction of Aqueous Nucleosides and Nucleotides via Photoelectron Spectroscopy Augmented by ab Initio Calculations. J. Am. Chem. Soc. 2015, 137 (1), 201–209. 10.1021/ja508149e. PubMed DOI

Dupuy R.; et al. Core level photoelectron spectroscopy of heterogeneous reactions at liquid–vapor interfaces: Current status, challenges, and prospects. J. Chem. Phys. 2021, 154 (6), 060901.10.1063/5.0036178. PubMed DOI

Seidel R.; Winter B.; Bradforth S. E. Valence Electronic Structure of Aqueous Solutions: Insights from Photoelectron Spectroscopy. Annu. Rev. Phys. Chem. 2016, 67 (1), 283–305. 10.1146/annurev-physchem-040513-103715. PubMed DOI

Pohl M. N.; et al. Do water’s electrons care about electrolytes?. Chem. Sci. 2019, 10 (3), 848–865. 10.1039/C8SC03381A. PubMed DOI PMC

Cederbaum L. S.; Zobeley J.; Tarantelli F. Giant Intermolecular Decay and Fragmentation of Clusters. Phys. Rev. Lett. 1997, 79 (24), 4778.10.1103/PhysRevLett.79.4778. DOI

Gopakumar G.; et al. Probing aqueous ions with non-local Auger relaxation. Phys. Chem. Chem. Phys. 2022, 24 (15), 8661–8671. 10.1039/D2CP00227B. PubMed DOI PMC

Jahnke T.; et al. Interatomic and Intermolecular Coulombic Decay. Chem. Rev. 2020, 120 (20), 11295–11369. 10.1021/acs.chemrev.0c00106. PubMed DOI PMC

Langen P.; Hucho F. Karl Lohmann and the Discovery of ATP. Angew. Chem., Int. Ed. 2008, 47 (10), 1824–1827. 10.1002/anie.200702929. PubMed DOI

Boyer P. D.Energy, life, and ATP. Nobel Lecture, December 8, 1997. In Nobel Lectures Chemistry 1996 - 2000; Grenthe I., Ed.; World Scientific, 2003.

Kamerlin S. C. L.; et al. Why nature really chose phosphate. Q. Rev. Biophys. 2013, 46 (1), 1–132. 10.1017/S0033583512000157. PubMed DOI PMC

Müller W. E. G.; Schröder H. C.; Wang X. Inorganic Polyphosphates As Storage for and Generator of Metabolic Energy in the Extracellular Matrix. Chem. Rev. 2019, 119 (24), 12337–12374. 10.1021/acs.chemrev.9b00460. PubMed DOI PMC

Bonora M.; et al. ATP synthesis and storage. Purinergic Signal. 2012, 8 (3), 343–357. 10.1007/s11302-012-9305-8. PubMed DOI PMC

Zimmerman J. J.; von Saint A.-v. A.; McLaughlin J.. Chapter 74 - Cellular Respiration, in Pediatric Critical Care, 4th ed.; Fuhrman B.P., Zimmerman J.J., Eds.; Mosby: Saint Louis, 2011; pp 1058–1072.

Sigel H.; Griesser R. Nucleoside 5′-triphosphates: self-association, acid–base, and metal ion-binding properties in solution. Chem. Soc. Rev. 2005, 34 (10), 875–900. 10.1039/b505986k. PubMed DOI

Tribolet R.; Sigel H. Influence of the protonation degree on the self-association properties of adenosine 5′-triphosphate (ATP). Eur. J. Biochem. 1988, 170 (3), 617–626. 10.1111/j.1432-1033.1988.tb13742.x. PubMed DOI

Lightstone F. C.; et al. A first principles molecular dynamics simulation of the hydrated magnesium ion. Chem. Phys. Lett. 2001, 343 (5−6), 549–555. 10.1016/S0009-2614(01)00735-7. DOI

Glonek T. 31P NMR of Mg-ATP in dilute solutions: Complexation and exchange. Int. J. Biochem. 1992, 24 (10), 1533–1559. 10.1016/0020-711X(92)90171-V. PubMed DOI

Wilson J. E.; Chin A. Chelation of divalent cations by ATP, studied by titration calorimetry. Anal. Biochem. 1991, 193 (1), 16–19. 10.1016/0003-2697(91)90036-S. PubMed DOI

Buelens F. P.; et al. ATP–Magnesium Coordination: Protein Structure-Based Force Field Evaluation and Corrections. J. Chem. Theory Comput. 2021, 17 (3), 1922–1930. 10.1021/acs.jctc.0c01205. PubMed DOI PMC

Storer A. C.; Cornish-Bowden A. Concentration of MgATP2- and other ions in solution. Calculation of the true concentrations of species present in mixtures of associating ions. Biochem. J. 1976, 159 (1), 1–5. 10.1042/bj1590001. PubMed DOI PMC

Bock J. L.; et al. 25Mg NMR Studies of magnesium binding to erythrocyte constituents. J. Inorg. Biochem. 1991, 44 (2), 79–87. 10.1016/0162-0134(91)84020-A. PubMed DOI

Molla G. S.; et al. Mechanistic and kinetics elucidation of Mg2+/ATP molar ratio effect on glycerol kinase. Mol. Catal. 2018, 445, 36–42. 10.1016/j.mcat.2017.11.006. DOI

Szabó Z. Multinuclear NMR studies of the interaction of metal ions with adenine-nucleotides. Coord. Chem. Rev. 2008, 252 (21–22), 2362–2380. 10.1016/j.ccr.2008.03.002. DOI

Bishop E. O.; et al. A 31P-NMR study of mono- and dimagnesium complexes of adenosine 5′-triphosphate and model systems. Biochim. Biophys. Acta Bioenerg. 1981, 635 (1), 63–72. 10.1016/0005-2728(81)90007-4. PubMed DOI

Sari J. C.; et al. Microcalorimetric study of magnesium-adenosine triphosphate ternary complex. J. Bioenerg. Biomembr. 1982, 14 (3), 171–179. 10.1007/BF00745018. PubMed DOI

Sigel H. Isomeric equilibria in complexes of adenosine 5′-triphosphate with divalent metal ions. Eur. J. Biochem. 1987, 165 (1), 65–72. 10.1111/j.1432-1033.1987.tb11194.x. PubMed DOI

Sigel H.; Song B. Solution structures of nucleotide-metal ion complexes. Isomeric equilibria. Metal ions in biological systems 1996, 32, 135–135.

Frańska M.; et al. Gas-Phase Internal Ribose Residue Loss from Mg-ATP and Mg-ADP Complexes: Experimental and Theoretical Evidence for Phosphate-Mg-Adenine Interaction. J. Am. Soc. Mass Spectrom. 2022, 33 (8), 1474–1479. 10.1021/jasms.2c00071. PubMed DOI PMC

Matthies M.; Zundel G. Hydration and self-association of adenosine triphosphate, adenosine diphosphate, and their 1:1 complexes with magnesium(II) at various pH values: infrared investigations. J. Chem. Soc., Perkin Trans. 2 1977, (14), 1824–1830. 10.1039/p29770001824. DOI

Manchester K. L. Free energy ATP hydrolysis and phosphorylation potential. Biochem. Educ. 1980, 8 (3), 70–72. 10.1016/0307-4412(80)90043-6. DOI

Achbergerová L.; Nahálka J. Polyphosphate - an ancient energy source and active metabolic regulator. Microb. Cell Fact. 2011, 10 (1), 63.10.1186/1475-2859-10-63. PubMed DOI PMC

Harrison C. B.; Schulten K. Quantum and Classical Dynamics Simulations of ATP Hydrolysis in Solution. J. Chem. Theory Comput. 2012, 8 (7), 2328–2335. 10.1021/ct200886j. PubMed DOI PMC

Akola J.; Jones R. O. ATP Hydrolysis in Water – A Density Functional Study. J. Phys. Chem. B 2003, 107 (42), 11774–11783. 10.1021/jp035538g. DOI

Wang C.; Huang W.; Liao J.-L. QM/MM Investigation of ATP Hydrolysis in Aqueous Solution. J. Phys. Chem. B 2015, 119 (9), 3720–3726. 10.1021/jp512960e. PubMed DOI

Kamerlin S.; Warshel A. On the energetics of ATP hydrolysis in solution. J. Phys. Chem. B 2009, 113 (47), 15692–15698. 10.1021/jp907223t. PubMed DOI

Weber J.; Senior A. E. ATP synthase: what we know about ATP hydrolysis and what we do not know about ATP synthesis. Biochim. Biophys. Acta Bioenerg. 2000, 1458 (2−3), 300–309. 10.1016/S0005-2728(00)00082-7. PubMed DOI

Liao J. C.; et al. The conformational states of Mg.ATP in water. Eur. Biophys J. 2004, 33 (1), 29–37. 10.1007/s00249-003-0339-2. PubMed DOI

Huang S. L.; Tsai M. D. Does the magnesium(II) ion interact with the α-phosphate of ATP? An investigation by oxygen-17 nuclear magnetic resonance. Biochemistry 1982, 21 (5), 951–959. 10.1021/bi00534a021. PubMed DOI

Mildvan A. S. Role of magnesium and other divalent cations in ATP-utilizing enzymes. Magnesium 1987, 6 (1), 28–33. PubMed

Rajendran T. E.; Muthukumarasamy T. Thermodynamic calculations of biochemical reaction systems at specified pH, pMg, and change in binding of hydrogen and magnesium ions. Asia-Pac. J. Chem. Eng. 2018, 13 (4), e220510.1002/apj.2205. DOI

Starikov E. B.; Panas I.; Nordén B. Chemical-to-Mechanical Energy Conversion in Biomacromolecular Machines: A Plasmon and Optimum Control Theory for Directional Work. 1. General Considerations. J. Phys. Chem. B 2008, 112 (28), 8319–8329. 10.1021/jp801580d. PubMed DOI

George P.; et al. “Squiggle-H2O”. An enquiry into the importance of solvation effects in phosphate ester and anhydride reactions. Biochim. Biophys. Acta Bioenerg. 1970, 223 (1), 1–15. 10.1016/0005-2728(70)90126-X. PubMed DOI

Shikama K. Standard free energy maps for the hydrolysis of ATP as a function of pH, pMg and pCa. Arch. Biochem. Biophys. 1971, 147 (1), 311–317. 10.1016/0003-9861(71)90338-9. PubMed DOI

Holm N. G. The significance of Mg in prebiotic geochemistry. Geobiology 2012, 10, 269–79. 10.1111/j.1472-4669.2012.00323.x. PubMed DOI PMC

Admiraal S. J.; Herschlag D. Mapping the transition state for ATP hydrolysis: implications for enzymatic catalysis. Chem. Biol. 1995, 2 (11), 729–739. 10.1016/1074-5521(95)90101-9. PubMed DOI

Alberty R. A. Enzymes: Units of biological structure and function. J. Chem. Educ. 1957, 34 (1), A33.10.1021/ed034pA33. DOI

Sigel H. Interactions of metal ions with nucleotides and nucleic acids and their constituents. Chem. Soc. Rev. 1993, 22 (4), 255–267. 10.1039/cs9932200255. DOI

Winter B.; Faubel M. Photoemission from Liquid Aqueous Solutions. Chem. Rev. 2006, 106 (4), 1176–1211. 10.1021/cr040381p. PubMed DOI

Ottosson N.; et al. On the Origins of Core–Electron Chemical Shifts of Small Biomolecules in Aqueous Solution: Insights from Photoemission and ab Initio Calculations of Glycineaq. J. Am. Chem. Soc. 2011, 133 (9), 3120–3130. 10.1021/ja110321q. PubMed DOI

Nolting D.; et al. pH-Induced Protonation of Lysine in Aqueous Solution Causes Chemical Shifts in X-ray Photoelectron Spectroscopy. J. Am. Chem. Soc. 2007, 129 (45), 14068–14073. 10.1021/ja072971l. PubMed DOI

Bruce J. P.; Hemminger J. C. Characterization of Fe2+ Aqueous Solutions with Liquid Jet X-ray Photoelectron Spectroscopy: Chloride Depletion at the Liquid/Vapor Interface Due to Complexation with Fe2+. J. Phys. Chem. B 2019, 123 (39), 8285–8290. 10.1021/acs.jpcb.9b06515. PubMed DOI

Aziz E. F.; et al. Interaction between liquid water and hydroxide revealed by core-hole de-excitation. Nature 2008, 455 (7209), 89–91. 10.1038/nature07252. PubMed DOI

Skitnevskaya A. D.; et al. Two-Sided Impact of Water on the Relaxation of Inner-Valence Vacancies of Biologically Relevant Molecules. J. Phys. Chem. Lett. 2023, 14, 1418–1426. 10.1021/acs.jpclett.2c03654. PubMed DOI

Mathe Z.; et al. Phosphorus Kβ X-ray emission spectroscopy detects non-covalent interactions of phosphate biomolecules in situ. Chem. Sci. 2021, 12 (22), 7888–7901. 10.1039/D1SC01266E. PubMed DOI PMC

Lanir A.; Yu N.-T. A Raman spectroscopic study of the interaction of divalent metal ions with adenine moiety of adenosine 5′-triphosphate. J. Biol. Chem. 1979, 254 (13), 5882–5887. 10.1016/S0021-9258(18)50496-8. PubMed DOI

Cohn M.; Hughes T. R. Jr. Nuclear Magnetic Resonance Spectra of Adenosine Di- and Triphosphate: II. Effect of Complexing with Divalent Metal Ions. J. Biol. Chem. 1962, 237 (1), 176–181. 10.1016/S0021-9258(18)81382-5. PubMed DOI

McFadden R. M. L.; et al. Magnesium(II)-ATP Complexes in 1-Ethyl-3-Methylimidazolium Acetate Solutions Characterized by 31Mg β-Radiation-Detected NMR Spectroscopy. Angew. Chem., Int. Ed. 2022, 61 (35), e20220713710.1002/anie.202207137. PubMed DOI PMC

Castellani M. E.; Avagliano D.; Verlet J. R. R. Ultrafast Dynamics of the Isolated Adenosine-5′-triphosphate Dianion Probed by Time-Resolved Photoelectron Imaging. J. Phys. Chem. A 2021, 125 (17), 3646–3652. 10.1021/acs.jpca.1c01646. PubMed DOI

Shimada H.; et al. Structural changes of nucleic acid base in aqueous solution as observed in X-ray absorption near edge structure (XANES). Chem. Phys. Lett. 2014, 591, 137–141. 10.1016/j.cplett.2013.11.026. PubMed DOI

Kelly D. N.; et al. Communication: Near edge x-ray absorption fine structure spectroscopy of aqueous adenosine triphosphate at the carbon and nitrogen K-edges. J. Chem. Phys. 2010, 133 (10), 101103.10.1063/1.3478548. PubMed DOI

Wang P.; et al. Thermodynamic parameters for the interaction of adenosine 5′-diphosphate, and adenosine 5′-triphosphate with Mg2+ from 323.15 to 398.15 K. J. Solution Chem. 1995, 24 (10), 989–1012. 10.1007/BF00973517. DOI

Viefhaus J.; et al. The Variable Polarization XUV Beamline P04 at PETRA III: Optics, mechanics and their performance. Nucl. Instrum. Methods Phys. Res. A 2013, 710, 151–154. 10.1016/j.nima.2012.10.110. DOI

Malerz S.; et al. A setup for studies of photoelectron circular dichroism from chiral molecules in aqueous solution. Rev. Sci. Instrum. 2022, 93 (1), 015101.10.1063/5.0072346. PubMed DOI

Winter B. Liquid microjet for photoelectron spectroscopy. Nucl. Instrum. Methods Phys. Res. A 2009, 601 (1−2), 139–150. 10.1016/j.nima.2008.12.108. DOI

Gilbert A. T. B.; Besley N. A.; Gill P. M. W. Self-Consistent Field Calculations of Excited States Using the Maximum Overlap Method (MOM). J. Phys. Chem. A 2008, 112 (50), 13164–13171. 10.1021/jp801738f. PubMed DOI

Epifanovsky E.; et al. Software for the frontiers of quantum chemistry: An overview of developments in the Q-Chem 5 package. J. Chem. Phys. 2021, 155 (8), 084801.10.1063/5.0055522. PubMed DOI PMC

Macetti G.; Genoni A. Initial Maximum Overlap Method for Large Systems by the Quantum Mechanics/Extremely Localized Molecular Orbital Embedding Technique. J. Chem. Theory Comput. 2021, 17 (7), 4169–4182. 10.1021/acs.jctc.1c00388. PubMed DOI

Mennucci B.; Tomasi J. Continuum solvation models: A new approach to the problem of solute’s charge distribution and cavity boundaries. J. Chem. Phys. 1997, 106 (12), 5151–5158. 10.1063/1.473558. DOI

Cancès E.; Mennucci B.; Tomasi J. A new integral equation formalism for the polarizable continuum model: Theoretical background and applications to isotropic and anisotropic dielectrics. J. Chem. Phys. 1997, 107 (8), 3032–3041. 10.1063/1.474659. DOI

Xu L.; Coote M. L. Improving the Accuracy of PCM-UAHF and PCM-UAKS Calculations Using Optimized Electrostatic Scaling Factors. J. Chem. Theory Comput. 2019, 15 (12), 6958–6967. 10.1021/acs.jctc.9b00888. PubMed DOI

Frisch M. J.; Schlegel H. B.; Scuseria G. E.; Robb M. A.; Cheeseman J. R.; Scalmani G.; Barone V.; Mennucci B.; Petersson G. A.; Nakatsuji H.; Caricato M.; Li X.; Hratchian H. P.; Izmaylov A. F.; Bloino J.; Zheng G.; Sonnenberg J. L.; Hada M.; Ehara M.; Toyota K.; Fukuda R.; Hasegawa J.; Ishida M.; Nakajima T.; Honda Y.; Kitao O.; Nakai H.; Vreven T.; Montgomery J. A. Jr.; Peralta J. E.; Ogliaro F.; Bearpark M.; Heyd J. J.; Brothers E.; Kudin K. N.; Staroverov V. N.; Keith T.; Kobayashi R.; Normand J.; Raghavachari K.; Rendell A.; Burant J. C.; Iyengar S. S.; Tomasi J.; Cossi M.; Rega N.; Millam J. M.; Klene M.; Knox J. E.; Cross J. B.; Bakken V.; Adamo C.; Jaramillo J.; Gomperts R.; Stratmann R. E.; Yazyev O.; Austin A. J.; Cammi R.; Pomelli C.; Ochterski J. W.; Martin R. L.; Morokuma K.; Zakrzewski V. G.; Voth G. A.; Salvador P.; Dannenberg J. J.; Dapprich S.; Daniels A. D.; Farkas O.; Foresman J. B.; Ortiz J. V.; Cioslowski J.; Fox D. J.. Gaussian 09, Revision D.01; Gaussian Inc.: Wallingford CT, 2013.

Yanai T.; Tew D. P.; Handy N. C. A new hybrid exchange–correlation functional using the Coulomb-attenuating method (CAM-B3LYP). Chem. Phys. Lett. 2004, 393 (1−3), 51–57. 10.1016/j.cplett.2004.06.011. DOI

Pugini M.; et al. How to measure work functions from aqueous solutions. Chem. Sci. 2023, 14 (35), 9574–9588. 10.1039/D3SC01740K. PubMed DOI PMC

Trofimov A. B.; et al. Photoelectron spectra of the nucleobases cytosine, thymine and adenine. J. Phys. B: At. Mol. Opt. Phys. 2006, 39 (2), 305.10.1088/0953-4075/39/2/007. DOI

Sherwood P. M. A. Introduction to Studies of Phosphorus-Oxygen Compounds by XPS. Surf. Sci. Spectra 2002, 9 (1), 62–66. 10.1116/11.20030101. DOI

Öhrwall G.; et al. Charge Dependence of Solvent-Mediated Intermolecular Coster–Kronig Decay Dynamics of Aqueous Ions. J. Phys. Chem. B 2010, 114 (51), 17057–17061. 10.1021/jp108956v. PubMed DOI

Rizkalla E. N.; Antonious M. S.; Anis S. S. X-ray photoelectron and potentiometric studies of some calcium complexes. Inorg. Chim. Acta 1985, 96 (2), 171–178. 10.1016/S0020-1693(00)87577-5. DOI

Kumar G.; et al. The influence of aqueous solvent on the electronic structure and non-adiabatic dynamics of indole explored by liquid-jet photoelectron spectroscopy. Faraday Discuss. 2018, 212, 359–381. 10.1039/C8FD00123E. PubMed DOI

From Gas to Solution: The Changing Neutral Structure of Proline upon Solvation

Liquid-jet photoemission spectroscopy as a structural tool: site-specific acid-base chemistry of vitamin C