Elucidating the structures of ionic clusters, from ion-water complexes to ion-biomolecule-water complexes

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ELUCIDATING THE STRUCTURES OF IONIC CLUSTERS, FROM ION-WATER COMPLEXES TO ION-BIOMOLECULE-WATER COMPLEXES

BY HAOCHEN KE

DISSERTATION

Submitted in partial fulfillment of the requirements

for the degree of Doctor of Philosophy in Mechanical Engineering in the Graduate College of the

University of Illinois at Urbana-Champaign, 2015

Urbana, Illinois

Doctoral Committee:

Professor Nick G. Glumac, Chair

Professor James M. Lisy, Director of Research Professor Martin Gruebele

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Abstract

The competition and cooperation between various noncovalent interactions in hydrated ions and hydrated ion-biomolecule systems are systematically characterized and examined using infrared spectroscopy and various theoretical approaches.

The Multiple Channel InfraRed PhotoDissociation spectroscopy (MC-IRPD) method is further developed and applied to argon-tagged hydrated alkali cation systems, M+(H2O)nAr (M = Li, Na, K, Rb, Cs; n = 3-5) with simultaneous monitoring of the [Ar] and [Ar+H2O]

fragmentation channels. The comparison between spectral features in the two channels and corresponding energy analyses provide definitive spectral assignments of the stable structural conformers and substantial insights of hydration mechanism of the cations. Results revealed that smaller cations (Li+ and Na+), with higher charge density, prefer to form structural configurations with extended linear networks of hydrogen bonds. Larger cations (Rb+ and Cs+), with lower charge density, prefer to generate configurations with cyclic hydrogen-bonded water subunits. It appears that K+ is somewhat unique with very simple (and predominantly) single structural conformers. This has led to the suggestion that K+ can "move" easily in or through biological systems, concealing its identity as an ion, under the "appearance" or disguise as a water molecule.

Indole is used as tractable model to study the hydration structures of biomolecules as well as the interplay of non-covalent interactions within ion-biomolecule-water complexes. With three potential binding sites: above the six- or five-member ring, and the N-H group, the

competition between π and hydrogen bond interactions involves multiple locations. Electrostatic interactions from monovalent cations are in direct competition with hydrogen bonding

interactions, as structural configurations involving both direct cation-indole interactions and cation-water-indole bridging interactions (π-hydrogen bond) were observed. The different charge

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densities of Na+/K+ give rise to different structural conformers at the same level of hydration. Infrared spectra with parallel Density Function Theory (DFT) calculations and Gibbs free energy calculations revealed rich structural insights of Na+/K+(Indole)(H2O)3-6 cluster ion complexes. Isotopic (H/D) analyses were applied to decouple the spectral features originating from the OH and NH stretches. Results showed no evidence of direct interaction between water and NH group of indole (via a σ-hydrogen bond) at current levels of hydration with the incorporation of cations, however π-hydrogen bonding interactions were ubiquitous at hydration levels between two and five.

Density Functional Theory based ab initio Molecular Dynamics simulations (DFT-MD) are applied to analyze the anharmonic coupling of O-H stretching modes and large amplitude intermolecular rocking modes in the water-nitrite complex system (H2O)-(NO2)-. MD simulated spectra reproduced earlier IR-IR double resonance spectra of water-nitrite remarkably well. Thorough analyses of dynamic trajectories revealed two distinct dynamic patterns, large amplitude symmetric rocking motion and asymmetric rocking motion, which yield completely different spectral features. Systematic application of autocorrelation functions, using Fourier transforms, of chosen dynamic parameters provided unambiguous assignments of both overall infrared spectra and motion-specific infrared spectra. DFT-MD simulations are proved to be a promising and powerful alternative tool in studying systems with anharmonic couplings, considering its reasonable computational cost, easy accessibility and sufficient accuracy.

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Acknowledgements

First and foremost, I would like to thank my parents, Mr. Ming Ke and Mrs. Ying Li, who have been a constant source of support, encouragement and understanding for me

throughout my five years as a graduate student here at University of Illinois, a place 6,600 miles from my home. As the only child in my family that bares all of my parents’ love and expectation, I hope this prestigious title, adventurous journey as well as unprecedented endeavor will

compensate, at least in part, for the sacrifices they have made in the past five years. Academically and professionally, I could not have achieved this goal without my

research advisor Professor James Lisy from Department of Chemistry and my academic advisor and committee chair Professor Nick Glumac from Department of Mechanical Science and Engineering. Professor Lisy, as a great mentor, colleague and friend, offered me the opportunity, and above all, the trust, to conduct leading edge research in the area of molecular spectroscopy, a rare topic for student with Mechanical Engineering background. With Professor Lisy’s guidance, encouragement and advice, I was able to make continuous improvement in the field of science in the past few years. Professor Glumac, who guided my Master’s research project, offered me continuous advice and support throughout my graduate study.

I would also like to show my gratitude to Professor Benjamin McCall and his group for the support and company they offered me in the past three years. Professor Marie-Pierre Gaigeot and her students, Sacha Abadie and Jérôme Mahe, offered me great support and company during my visit in France. Dr. Amy Nicely and Dr. Christian van der Linde, as my colleagues, offered me great support on my research projects and added fun to my scientific journey.

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I would also like to thank the many friends that I have made while attending University of Illinois, as well as those old friends back in Beijing, with whom I shared my happiness and sorrow along the journey. I am very fortunate to have met such great people.

My appreciation is extended to the outstanding support from the School of Chemical Science and Department of Mechanical Science and Engineering staff who have been instrumental in my success here at University of Illinois. My Doctoral Qualifying Exam Committee (Prof. Quinn Brewster, Prof. Scott Stewart and Prof. Kimani Toussaint), my

Preliminary Exam Committee (Prof. James Lisy, Prof. Nick Glumac, Prof. Benjamin McCall and Prof. Gary Eden), and my Final Exam Committee (Prof. James Lisy, Prof. Nick Glumac, Prof. Benjamin McCall and Prof. Martin Gruebele) offered me great scientific feedback.

Finally, I would like to thank the National Science Foundation, as well as Department of Chemistry and Department of Mechanical Science and Engineering for financially support my study and research.

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Chapter 1: Introduction

1.1 Background

The competition between various noncovalent interactions, such as van der Waals, electrostatic and hydrogen bonding interactions, plays a key role in determining the hydration structures and thermodynamic properties of biologically relevant molecules, such as proteins,1–4 DNA5–7 and RNA8,9 in biological media.10–18 The properties of biologically relevant molecules are closely related to their often unique biological functionalities. Systematic characterization of the hydration structures and thermodynamic properties of biomolecules in a biologically relevant medium has long been a challenge. As water molecules and ions are ubiquitous in physiological systems, many-body interactions between water molecules, ions and different functional groups of biomolecules have to be accounted for properly.19–26 Water can interact either with different functional groups within biomolecules, or with ions (K+, Na+, Cl- and etc.) and other water molecules in intra- or extracellular fluids. The ordering of such interactions is largely affected by the charge density of the ion, ion concentrations, as well as temperature.27

Alkali metal cations play vital roles in chemical and physiological systems. Lithium is widely used in psychiatric treatment of manic states and bipolar disorder;7,28 Sodium and potassium are essential elements, having major biological roles as electrolytes, balancing osmotic pressure in cells and assisting electroneurographic signal transmission;29 Rubidium has seen increasing usage as a supplement for manic depression and the treatment of depression;30–32 Cesium-doped compounds are used as essential catalysts in chemical production and organic synthesis.33,34 Since hydrated alkali metal cations are ubiquitous in chemical and biochemical systems, their structural and thermodynamic properties are essential in characterizing complex

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chemical and physiological processes, such as ion transport and ion size-selectivity by ionophores and protein ion channels.19–26

In order to quantitatively understand how noncovalent interactions affect the hydration of biomolecules, simple biomolecules with fewer functional groups are often chosen as tractable models for studying the hydration of more complex biomolecules with additional functional groups.27,35–38 Indole is one of the most important tractable models, as the indole moiety is found in many important, biologically relevant molecules, such as the neurotransmitter, serotonin,39,40 its precursor tryptophan, the pineal hormone, melatonin,41,42 anticancer indole-3-carbonal43–46 and a group of antitumor agents, the arylthioindoles.47 The alkali-cationized indole water cluster is a perfect system for the quantitative and systematic study of the hydration structures of ion-biomolecules complexes resulting from the competition and cooperation of noncovalent interactions. Cation-water and cation-indole electrostatic interactions can be adjusted by introducing monovalent cations with different charge densities; hydrogen bonding interactions between water molecules and between water and indole can be modulated by varying the level of hydration of ion-biomolecules complexes.

Many other issues make the characterization of the biological functionalities of biomolecules even more challenging. In order to obtain detailed structural information and precise thermodynamic properties, gas phase spectroscopy is often applied.48 The traditional method, heating samples up to a temperature over its melting point, has been pushed to its limit, as the melting points of many biomolecules are very high (> 200 degree Celsius), close to their decomposition temperatures. Extreme caution has to be taken when handling the heated samples, which limited the choices of suitable biomolecules. Furthermore, due to the ion cluster

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could coexist along side the global minimum conformers, making the infrared spectroscopy more complicated.49,50 The interactions between different inter- and intramolecular motifs could also give rise to overlapping spectral features.38,51–53

Parallel theoretical calculations are usually applied in order to obtain detailed information of structures, molecular motions, relative energies and theoretical infrared spectra of the system of interest. Molecular geometric surveys are also required to map as many low energy

conformations as possible. Ab initio static quantum calculations are the most widely used method for simulating the structure of gas phase cluster ions.38,49,51,52,54–59 However, due to the lack of computational power, compromises have to be made between accuracy and computational cost.49,58,59 Furthermore, the intrinsic double harmonic approximations (potential energy and dipole moment surfaces) of this method limit its accuracy when being used to analyze systems with substantial anharmonicity and/or at finite temperature (~ 300 K).60

The major focus of this thesis is to quantitatively investigate the hydration structures, thermodynamic properties and orderings of non-covalent interactions of hydrated cations and hydrated ion-biomolecule complexes, laying the foundation for exploring the functionalities of biomolecules in real physiological media. Novel InfraRed PhotoDissociation (IRPD) techniques and comprehensive structural analyzing methods were developed and applied to specific systems to tackle these challenges. Ab initio quantum calculations as well as Density Functional Theory based Born-Oppenheimer Molecular Dynamics (DFT-MD) simulations were applied to help understand and interpret the IRPD experimental results.

1.2 Investigation Method

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vibrations are highly sensitive to both ion-molecule interactions and hydrogen bonding. Hydrogen bond formation, via proton donation, results in a shift to lower frequency and an increase in IR intensity for donating O-H groups while accepting O-H groups are relatively unaffected.54,61–63 The magnitude of the frequency shift is related to the strength of the hydrogen bond49,58,64–66 and can range from a few cm-1 for weak bonds to hundreds of cm-1 for the strongest interactions. O-H and other hydride modes are also directly affected by alkali metal ions. For example, O-H stretch modes in neutral water molecules shift to lower frequency upon complexation to alkali metal ions as a result of the strong ion-molecule electrostatic interaction.67 Again, the magnitude of this shift is dependent on the strength of the non-covalent interaction.67 Thus, IRPD spectroscopy is useful for structural characterization (different configurations will have different O-H stretch vibrational frequencies) as well as probing the relative strengths of the different non-covalent interactions in cluster ions.

The evaporative cooling processes associated with the formation of cluster ions can result in clusters with considerable amounts of internal energy,68–75 which translates to effective

temperatures of ~ 250 K or higher for hydrogen bonded solvents.66,68,75–77 At these temperatures, the spectral resolution of the infrared spectra is sometimes insufficient, due to thermal

broadening, to reveal fine spectral features originating from various O-H stretching modes. Lee and co-workers,78–81 followed by Johnson and coworkers82–87 have developed a method to lower the effective temperatures of cluster ions. They incorporated argon into the nascent cluster ion ensemble, which reduced the internal energy of cluster ion by a factor of five to ten, resulting in cluster ions with effective temperatures of ~50K. This argon-tagged IRPD spectroscopy was first introduce into the Lisy lab by Vaden and coworkers in the early 2000s.75 Since then, various systems have been investigated using similar techniques.66,88 Rice–Ramsperger–Kassel–Marcus

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(RRKM) and Evaporative Ensemble (EE) based theoretical investigations were performed by Cabarcos, Weinheimer and co-workers.74 The RRKM-EE derived theoretical cluster ion effective temperatures agree remarkably well with effective temperatures obtained from the relative

intensities of K rotational spectral features in IRPD spectra of ion clusters produced by the evaporatively-cooled ion source,58,66,75,88 as well as collisionally-cooled ion source.88

Further experimental investigations of the hydrated alkali metal cations led by Miller and co-workers revealed that the effective temperature had substantial effects on the preferred cluster ion conformations.49,58,59 Higher energy conformations could coexist with global minimum energy conformation for argon tagged cluster ions. Similar temperature dependences of cluster ion conformation were also observed in systems of hydrated ion biomolecule complexes, of Nicely and co-workers.51–53 Rodriguez and co-workers first introduced a novel Multiple Channel IRPD (MC-IRPD) method and their preliminary results revealed substantial evidence for the existence of high energy conformers in Li+(H2O)4 system.50 These results encourage researchers to carry out similar investigations to study the hydration structures and dynamics of

physiologically relevant ions (K+, Na+, Cl- and etc.), which are of vital importance in modeling biochemical and physiological processes. Multiple photon dissociation effects in hydrated alkalis metal ions were demonstrated and systematically investigated by Beck and co-workers.89 Results indicate that photon induced dissociation involving only single photon absorption is the

predominant dissociation mechanism in current eperimental set-up.89 This enables researchers to quantitatively extract binding energies of dissociating ligands by monitoring parallel dissociation channels in IRPD experiments.90

IRPD spectroscopy was also applied to study hydrated ion biomolecule complexes. Miller and co-workers made the first attempt to investigate hydration process and temperature

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effects of hydrated ion-indole38 and ion-(N-methylacetamide) complexes.57 Nicely and co-worker carried out similar investigations of hydrated ion-Tryptamine51,52 and ion-(2-amino-1-phenyl ethanol) systems.53 Rodriguez and co-workers extended investigations to ion-crown ether complexes, attempting to establish qualitative models of ionophore systems.91–95 Several hydrated ion-neurotransmitter systems (Ephedrine, Pseudoephedrine and Serotonin ) were also attempted by Nicely and co-workers, but were less successful than earlier studies. One reason is that the melting points of these relatively large molecules are on the order of 200 C, which pushed the heated ion source to its limit. Another reason is that the infrared spectra in the

spectral region of interest (3300 cm-1 ~ 3800 cm-1) are very complicated, containing overlapping spectral features originated from both O-H and N-H stretching modes.38 Without systematic decoupling of O-H and N-H stretching motions, one cannot make definitive spectral assignments and structural analyses. Isotopic (H/D) analyses have been widely used to unravel closely

overlapping spectral features.96–101 Therefore, we attempted to incorporate isotopic (H/D) analyses into the traditional IRPD spectroscopy to resolve the overlapping issue and to make definitive structural analyses on hydrated ion-biomolecule complexes.

Parallel ab initio calculations were applied with appropriate choice of functional and basis set to provide theoretical support, such as information about structural conformations, energetics and theoretical vibrational frequencies. Rice-Ramsperger-Kassel-Marcus Evaporative Ensemble (RRKM-EE)74 formulism was applied to estimate the effective temperatures of cluster ion systems. Density Functional Theory based Molecular Dynamic simulations (DFT-MD)60 were applied in addition to ab initio calculations to systems that possess highly anharmonic motion. A detailed literature review and description of the theoretical tools used in this thesis will be given in section 2.2.

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1.3 Overview of Thesis Chapters

A detailed overall description of the experimental apparatus in Lisy lab and quantum chemical calculations and molecular dynamics simulations will be provided in chapter 2. The particular experimental set-up and calculation methods used for each system will be described in greater detail in the chapter discussing that system.

The hydration of alkali cations yields a variety of structural conformers with varying numbers of water molecules in the first solvation shell. How these ions move from the aqueous phase into biological systems, such as at the entrance of an ion channel, depends on the interplay between competing intermolecular forces, which first must involve ion-water and water-water interactions.

In chapter 3, InfraRed PhotoDissociation (IRPD) spectra of M+(H2O)nAr (M = Rb, Cs; n = 3-5) with simultaneous monitoring of [Ar] and [Ar+H2O] fragmentation channels are reported. The comparison between the spectral features in the two channels and corresponding energy analysis provide spectral assignments of the stable structural conformers, thermodynamic data of photodissociation process and insight into the competition between ion---water electrostatic and water---water hydrogen bonding interactions.

In chapter 4, new infrared action spectra, using argon as a messenger or "spy", for Li+, Na+, and K+, with up to five water molecules are reported, and new structural conformers identified from ab initio calculations, combined with previous results on Rb+ and Cs+, have characterized structural transitions at each hydration level.

In chapter 5, Indole is used as tractable model for the quantitative and systematic study of the hydration structures of ion-biomolecules complexes as a result of competition and

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can be adjusted by introducing monovalent cations with various charge densities; hydrogen bonding interactions between water molecules and between water and indole can be modulated by varying the level of hydration of ion-biomolecules complexes. A comprehensive analysis method was developed, that combines IRPD spectra with ab initio calculations, Gibbs free energy calculations and isotopic (H/D) analysis, to systematically study the structures of cation-indole-water complexes and to improve the models of hydration and other thermodynamic processes involving biologically relevant molecules.

In chapter 6, Density Functional Theory based Molecular Dynamic simulations (DFT-MD) are applied to water-nitrite complex system. The isomer specific IR-IR double resonance spectroscopy done by Johnson and co-workers102 clearly revealed the anharmonic coupling of O-H stretching motions with large amplitude intermolecular rocking motions. O-However, traditional ab initio calculations cannot reproduce these highly amharmonic interactions with reasonable accuracy and efficiency simultaneously. The main purpose of this chapter is to demonstrate that, by choosing appropriate functional and basis sets, DFT-MD simulations can reproduce the large amplitude intermolecular rocking motions observed in the water nitrite complex system, with good accuracy and reasonable computational cost.

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(53) Brites, V.; Nicely, A. L.; Sieffert, N.; Gaigeot, M.-P.; Lisy, J. M. High Energy Conformers of M+(APE)(H2O)0-1Ar0-1 Clusters Revealed by Combined IR-PD and DFT-MD Anharmonic Vibrational Spectroscopy. Phys. Chem. Chem. Phys. 2014, 16, 13086–13095.

(54) Zwier, T. S. The Spectroscopy of Solvation in Hydrogen-bonded Aromatic Clusters. Annu. Rev. Phys. Chem. 1996, 47, 205–241.

(55) Carney, J. R.; Zwier, T. S. Infrared and Ultraviolet Spectroscopy of Water-Containing Clusters of Indole, 1-Methylindole, and 3-Methylindole. J. Phys. Chem. A. 1999, 103, 9943– 9957.

(56) Chang, T. M.; Chakrabarty, S.; Williams, E. R. Hydration of Gaseous m-Aminobenzoic Acid: Ionic vs Neutral Hydrogen Bonding and Water Bridges. J. Am. Chem. Soc. 2014, 136, 10440–10449.

(57) Miller, D. J.; Lisy, J. M. Modeling Competitive Interactions in Proteins: Vibrational Spectroscopy of M+(n-methylacetamide)1(H2O)n=0-3, M = Na and K, in the 3μ Region.J. Phys. Chem. A. 2007, 111, 12409–12416.

(58) Miller, D. J.; Lisy, J. M. Entropic Effects on Hydrated Alkali-Metal Cations: Infrared Spectroscopy and ab Initio Calculations of M+(H2O)x=2−5 Cluster Ions for M = Li, Na, K, and Cs. J. Am. Chem. Soc. 2008, 130, 15393–15404.

(59) Nicely, A. L.; Miller, D. J.; Lisy, J. M. Gas-phase Vibrational Spectroscopy and ab initio Calculations of Rb+(H2O)n and Rb+(H2O)nAr Cluster Ions. J. Mol. Spectrosc. 2009, 257, 157– 163.

(60) Gaigeot, M.-P. Theoretical Spectroscopy of Floppy Peptides at Room Temperature. A DFTMD Perspective: Gas and Aqueous Phase. Phys. Chem. Chem. Phys. 2010, 12, 3336–3359. (61) Del Bene, J. E.; Jordan, M. J. T. Vibrational Spectroscopy of the Hydrogen Bond: An ab initio Quantum-chemical Perspective. Int. Rev. Phys. Chem. 1999, 18, 119–162.

(62) Xantheas, S. S.; Dunning, T. H. Ab initio Studies of Cyclic Water Clusters (H2O)n, n=1–6. I. Optimal Structures and Vibrational Spectra. J. Chem. Phys. 1993, 99, 8774–8792.

(63) Huisken, F.; Kaloudis, M.; Kulcke, A. Infrared Spectroscopy of Small Size-selected Water Clusters. J. Chem. Phys. 1996, 104, 17–25.

(64) Ke, H.; van der Linde, C.; Lisy, J. M. Insights into the Structures of the Gas-Phase Hydrated Cations M+(H2O)nAr (M = Li, Na, K, Rb, and Cs; n = 3–5) Using Infrared Photodissociation Spectroscopy and Thermodynamic Analysis. J. Phys. Chem. A. 2015, 119, 2037–2051. (65) Iwasaki, A.; Fujii, A.; Watanabe, T.; Ebata, T.; Mikami, N. Infrared Spectroscopy of

Hydrogen-Bonded Phenol−Amine Clusters in Supersonic Jets. J. Phys. Chem. 1996, 100, 16053– 16057.

(66) Vaden, T. D.; Weinheimer, C. J.; Lisy, J. M. Evaporatively Cooled M+(H2O)Ar Cluster Ions: Infrared Spectroscopy and Internal Energy Simulations. J. Chem. Phys. 2004, 121, 3102–3107. (67) Feller, D.; Glendening, E. D.; Woon, D. E.; Feyereisen, M. W. An Extended Basis Set ab initio Study of Alkali Metal Cation-water Clusters. J. Chem. Phys. 1995, 103, 3526–3542. (68) Draves, J. A.; Luthey‐Schulten, Z.; Liu, W.; Lisy, J. M. Gas-phase Methanol Solvation of Cs+. J. Chem. Phys. 1990, 93, 4589–4602.

(69) Nielsen, S. B.; Ayotte, P.; Kelley, J. A.; Johnson, M. A. Infrared Spectroscopic Observation of the Argon Isomer Distribution in Evaporative Ensembles of I(ROH)Arm(R=methyl, ethyl, isopropyl) Clusters. J. Chem. Phys. 1999, 111, 9593–9599.

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(70) Hansen, K.; Näher, U. Evaporation and Cluster Abundance Spectra. Phys. Rev. A. 1999, 60, 1240–1250.

(71) Bréchignac, C.; Busch, H.; Cahuzac, P.; Leygnier, J. Dissociation Pathways and Binding Energies of Lithium Clusters from Evaporation Experiments. J. Chem. Phys. 1994, 101, 6992– 7002.

(72) Wei, S.; Tzeng, W. B.; Castleman, A. W. Dissociation Dynamics: Measurements of Decay Fractions of Metastable Ammonia Cluster Ions. J. Chem. Phys. 1990, 93, 2506–2512.

(73) Lifshitz, C.; Iraqi, M.; Peres, T. Magic Numbers in Kinetic Energy Releases for

Unimolecular Decompositions of Proton-bound Acetone and Acetone/water Clusters. Rapid Commun. Mass Spectrom. 1990, 4, 485–487.

(74) Cabarcos, O. M.; Weinheimer, C. J.; Lisy, J. M. Modeling Internal Energy Distributions in Ion Clusters: Comparison between Experiment and Simulations. J. Phys. Chem. A. 1999, 103, 8777–8791.

(75) Vaden, T. D.; Forinash, B.; Lisy, J. M. Rotational Structure in the Asymmetric OH Stretch of Cs+(H2O)Ar. J. Chem. Phys. 2002, 117, 4628–4631.

(76) Cabarcos, O. M.; Lisy, J. M. Molecular Dynamics Simulation of Gas Phase Ion Cluster formation. Int. J. Mass. Spectrom. 1999, 185–187, 883–903.

(77) Weinheimer, C. J.; Lisy, J. M. Gas-Phase Cluster Ion Vibrational Spectroscopy of Na+(CH3OH)2-7.J. Phys. Chem. 1996, 100, 15305–15308.

(78) Okumura, M.; Yeh, L. I.; Myers, J. D.; Lee, Y. T. Infrared Spectra of the Solvated

Hydronium Ion: Vibrational Predissociation Spectroscopy of Mass-selected H3O+(H2O)n(H2)m. J. Phys. Chem. 1990, 94, 3416–3427.

(79) Yoshikawa, K.; Kusumi, T.; Ukitsu, M.; Nakata, S. Generation of Periodic Force with Oscillating Chemical Reaction. Chem. Phys. Lett. 1993, 211, 211–213.

(80) Okumura, M.; Yeh, L. I.; LEE, Y. T. Infrared Spectroscopy of the Cluster Ions H+(H2)n. J. Chem. Phys. 1988, 88, 79–91.

(81) Yeh, L. I.; Okumura, M.; Myers, J. D.; Price, J. M.; LEE, Y. T. Vibrational Spectroscopy of the Hydrated Hydronium Cluster Ions H3O+(H2O)n (n=1, 2, 3). J. Chem. Phys. 1989, 91, 7319 (82) Kelley, J. A.; Weber, J. M.; Lisle, K. M.; Robertson, W. H.; Ayotte, P.; Johnson, M. A. The Infrared Predissociation Spectra of Cl−·H2O·Arn (n=1a of Experimental Determination of the Influence of Ar Solvent Atoms. Chem. Phys. Lett. 2000, 327, 1–6.

(83) Weber, J. M.; Kelley, J. A.; Robertson, W. H.; Johnson, M. A. Hydration of a Structured Excess Charge Distribution: Infrared Spectroscopy of the O2−(H2O)n,)ct≤n≤5) clusters. J. Chem. Phys. 2001, 114, 2698–2706.

(84) Robertson, W. H.; Karapetian, K.; Ayotte, P.; Jordan, K. D.; Johnson, M. A. Infrared Predissociation Spectroscopy of I−(CH3OH)n,n=1,2: Cooperativity in Asymmetric Solvation. J. Chem. Phys. 2002, 116, 4853–4857.

(85) Ayotte, P.; Weddle, G. H.; Kim, J.; Johnson, M. A. Mass-selected “matrix isolation” Infrared Spectroscopy of the I−·(H2O)2 Complex: Making and Breaking the Inter-water Hydrogen-bond. Chem. Phys. 1998, 239, 485–491.

(86) Ayotte, P.; Weddle, G. H.; Johnson, M. A. An Infrared Study of the Competition between Hydrogen-bond Networking and Ionic Solvation: Halide-dependent Distortions of the Water Trimer in the X−(H2O)3,(X=Cl, Br, I) Systems. J. Chem. Phys. 1999, 110, 7129–7132.

(87) Ayotte, P.; Nielsen, S. B.; Weddle, G. H.; Johnson, M. A.; Xantheas, S. S. Spectroscopic Observation of Ion-Induced Water Dimer Dissociation in the X-·(H2O)2 (X = F, Cl, Br, I)

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(88) Vaden, T. D.; Lisy, J. M.; Carnegie, P. D.; Dinesh Pillai, E.; Duncan, M. A. Infrared Spectroscopy of the Li+(H2O)Ar Complex: the Role of Internal Energy and its Dependence on Ion Preparation. Phys. Chem. Chem. Phys. 2006, 8, 3078–3082.

(89) Beck, J. P.; Lisy, J. M. Infrared Spectroscopy of Hydrated Alkali Metal Cations: Evidence of Multiple Photon Absorption. J. Chem. Phys. 2011, 135, 44302.

(90) Ke, H.; van der Linde, C.; Lisy, J. M. Insights into Gas-Phase Structural Conformers of Hydrated Rubidium and Cesium Cations, M+(H2O)nAr (M = Rb, Cs; n = 3–5), Using Infrared Photodissociation Spectroscopy. J. Phys. Chem. A. 2014, 118, 1363–1373.

(91) Rodriguez, J. D.; Kim, D.; Tarakeshwar, P.; Lisy, J. M. Exploring Gas-Phase

Ion−Ionophore Interactions: Infrared Spectroscopy of Argon-Tagged Alkali Ion-Crown Ether Complexes. J. Phys. Chem. A. 2010, 114, 1514–1520.

(92) Rodriguez, J. D.; Lisy, J. M. Probing Ionophore Selectivity in Argon-Tagged Hydrated Alkali Metal Ion–Crown Ether Systems. J. Am. Chem. Soc. 2011, 133, 11136–11146. (93) Rodriguez, J. D.; Lisy, J. M. Infrared Spectroscopy of Multiply Charged Metal Ions: Methanol-Solvated Divalent Manganese 18-Crown-6 Ether Systems. J. Phys. Chem. A. 2009, 113, 6462–6467.

(94) Rodriguez, J. D.; Vaden, T. D.; Lisy, J. M. Infrared Spectroscopy of Ionophore-Model Systems: Hydrated Alkali Metal Ion 18-Crown-6 Ether Complexes. J. Am. Chem. Soc. 2009, 131, 17277–17285.

(95) Rodriguez, J. D.; Lisy, J. M. Infrared Spectroscopy of Gas-phase Hydrated K+:18-crown-6 complexes: Evidence for High Energy Conformer Trapping Using the Argon Tagging Method. Int. J. Mass. Spectrom. 2009, 283, 135–139.

(96) Matsuda, Y.; Ebata, T.; Mikami, N. Vibrational Spectroscopy of 2-pyridone and its Clusters in SupersonicJ: Structures of the Clusters as Revealed by Characteristic Shifts of the NH and C=O Bands. J. Chem. Phys. 1999, 110, 8397–8407.

(97) Noguchi, T.; Sugiura, M. Analysis of Flash-Induced FTIR Difference Spectra of the S-State Cycle in the Photosynthetic Water-Oxidizing Complex by Uniform 15N and 13C Isotope

Labeling†. Biochemistry. 2003, 42, 6035–6042.

(98) Weidner, T.; Breen, N. F.; Drobny, G. P.; Castner, D. G. Amide or Amine: Determining the Origin of the 3300 cm−1 NH Mode in Protein SFG Spectra Using 15N Isotope Labels. J. Phys. Chem. B. 2009, 113, 15423–15426.

(99) Marion, D.; Driscoll, P. C.; Kay, L. E.; Wingfield, P. T.; Bax, A.; Gronenborn, A. M.; Clore, G. M. Overcoming the Overlap Problem in the Assignment of Proton NMR Spectra of Larger Proteins. Biochemistry. 1989, 28, 6150–6156.

(100) Engdahl, A.; Nelander, B.; Åstrand, P. Complex Formation between Water and Formamide. J. Chem. Phys. 1993, 99, 4894–4907.

(101) Smirnov, S. N.; Golubev, N. S.; Denisov, G. S.; Benedict, H.; Schah-Mohammedi, P.; Limbach, H.-H. Hydrogen/Deuterium Isotope Effects on the NMR Chemical Shifts and Geometries of Intermolecular Low-Barrier Hydrogen-Bonded Complexes. J. Am. Chem. Soc.

1996, 118, 4094–4101.

(102) Elliott, B. M.; Relph, R. A.; Roscioli, J. R.; Bopp, J. C.; Gardenier, G. H.; Guasco, T. L.; Johnson, M. A. Isolating the Spectra of Cluster Ion Isomers using Ar-“tag” -mediated IR-IR Double Resonance within the Vibrational Manifolds: Application to NO2−H2O. J. Chem. Phys.

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Chapter 2: Technical Details

2.1 Experimental Details

All of the InfraRed PhotoDissociation experiments were conducted using a custom designed triple quadrupole mass selective infrared spectrometer (Figure 2.1). The experimental apparatus consists of two sections, a cluster generation and detection section, which have three differentially vacuumed chambers; and a tunable infrared light source. The details of the apparatus have been discussed previously by former group members.1–3 While the particular experimental set-up used for each system will be described in more detail in the chapter discussing that system, an overview of the apparatus will be presented here.

Figure 2.1 Schematic of the custom-designed triple quadrupole mass selective infrared spectrometer.

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while gas phase biologically relevant molecules are generated through a heated sample chamber maintained at ~10 degree Celsius above the melting temperature of the molecule. This gas mixture is introduced in to the source chamber through a 180 micrometer, 45 degree conical nozzle. Approximately 30 mm, or 160 nozzle diameters, downstream from the cluster source, the fully expanded neutral beam is perpendicularly intersected by an alkali ion beam. Ions are produced via thermionic emission from a resistively-heated tungsten filament coated with an alkali halide salt-impregnated paste. This collision and subsequent ion solvation forms an ensemble of unstable ion clusters with high internal energies. Through progressive rearrangement and loss of solvating ligands, as described by the evaporative ensemble, the nascent ion clusters lose both mass and internal energy until they reach a quasi-stable state, a state whose lifetime is long compared to the time required to completely travel through the detection chamber.

A set of electrostatic lenses images the nascent cluster ions on to a 1.5 millimeter diameter skimmer mounted on the interchamber wall. The ion beams are guided by a series of electrostatic lenses and an octupole ion guide while the clusters continue to evaporatively stabilize. As the ion clusters are reaching a quasi-stable state, they are mass selected by the first of three quadrupole mass filters. The mass-selected cluster ions then enter the second quadrupole (ion guiding only), where they interact with the axial output from a LaserVision optical parametric oscillator/optical parametric amplifier (OPO/OPA) pumped by the 1064 nm output from a 10 Hz Surelite II Nd:YAG laser (Continuum). While traveling though this interaction region, the mass-selected cluster ions can undergo photo-induced, spontaneous, and/or collisional dissociation, with photo-induced dissociation being the dominant cause of

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fragmentation, when the OPO laser is in resonance with an IR-active vibrational mode of the cluster ion.

The surviving parent cluster ions and the resulting cluster fragments are detected by the third, mass-analyzing quadrupole, which is tuned to a specific fragment mass to determine the extent of dissociation. Fragment ions are detected using a combination of a negatively charged (-3000 V) conversion dynode and positively charged (+1500 V ~ +(-3000 V) channeltron electron multiplier. To correct for any collisional or unimolecular dissociation events that may have occurred, the ion fragment signal is collected for similar times with the laser off. These signals are then subtracted from the laser-on signal to yield the corrected fragment ion intensity resulting from absorption of a single infrared photon.

The ion flight times (150-300 μsec) through the apparatus are used to set the timing gates required to select the signal from the fragmentation events within the interaction region. A single data acquisition computer handles both the data acquisition and mass and laser control. The photodissociation cross sections for the vibrational predissociation observed in the specified fragment channel are obtained from the relationship between the laser fluence and the fractional fragmentation, as is given in equation 2.1:

ln 1 ( ) f p I I F      _  _    (2.1) where I_f is the corrected fragment intensity, I_p is the parent ion intensity, F is the laser fluence, and  ( ) is the calculated photodissociation cross section. Frequency calibration is verified by concurrently acquiring the photoacoustic spectra of ambient water vapor (for OH stretching region, 3300 cm-1 ~ 3800 cm-1), or the absorption spectra of HCl held in a sealed

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experimental spectra reported in this thesis have been smoothed using a three-point, adjacent averaging algorithm.

2.2 Computational Details

In order to fully understand the gas phase infrared spectra, one usually needs to perform parallel theoretical calculations, obtaining detailed information of structures, molecular motions, relative energies and theoretical infrared spectra. Substantive geometry surveys are also required to map as many low energy conformations as possible. Traditionally, static ab initio (methods that solve the Schrödinger equation associated with the molecular Hamiltonian, which does not include any empirical or semi-empirical parameters) quantum chemical calculations using Gaussian software packages have been widely used to quantitatively characterize geometries, energies, and harmonic vibrational frequencies of molecular species to reasonably high degree of accuracy.1,4–12 However, compromises have to be made between level of accuracy and available computational power.1,9,10 When performing quantum chemical calculations, the level of

molecular orbital theory and the basis set (the set of functions used to create the molecular orbitals), have to be specified simultaneously. The most widely used molecular orbital theories include: Hartree-Fork method,13 semi-empirical quantum chemistry methods,14 Moller-Plesset perturbation theory,15 configuration interaction method16 and coupled cluster method,17,18 as ranked from lowest to highest complexity. Two of the most widely used basis sets are the Split-valence basis sets, first introduced by John Pople,19 and Correlation-consistent basis sets, first introduced by Dunning and coworkers.20

There is no certain rule determining how to choose the combination of level of molecular orbital theory and basis sets, as the level of accuracy of the calculations are very sensitive to the charge, size and extent of anharmonic interactions involved in the system. Therefore, different

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combinations of theory and basis sets have to be performed simultaneously, with results thoroughly examined, in order to find the combination that yields best results compared with experiments, and that fit in the computational power limit. Empirically, second order Moller-Plascet perturbation theory21–24 and Becke’s nonlinear three-parameter exchange and correction functional with the Lee-Yang-Parr correction method25,26 have been chosen for positively-charged ion cluster calculations.1,2,7–12,27–31

All of the ab initio static calculations were performed using Gaussian 09 package,32 with initial geometries and input parameters prepared using GaussView, Version 5 software.33 Ab initio calculations at the second order Moller-Plascet perturbation theory (MP2) level are used to identify stable structural configurations, conformational energies and vibrational frequencies for the M+(H2O)nAr (M = Li, Na, K, Rb and Cs; n = 3~5) systems. Oxygen, hydrogen and argon atoms as well as lithium and sodium cations were treated with the augmented

correlation-consistent all-electron basis set, aug-cc-pVDZ. The Los Alamos double-ζ basis set with effective core potentials LANL2DZ34–36 was used to treat potassium, rubidium and cesium cations. Ab initio calculations with less expensive hybrid density functional theory (DFT) based Becke’s nonlinear three-parameter exchange and correction functional with the Lee-Yang-Parr correction functional (B3LYP) were used to identify stable structural configurations, conformational

energies and vibrational frequencies for M+(Indole)(H2O)n (M = Na, K; n =3~6) systems, with all atoms treated with 6-31+G* basis sets. Basis-set superposition errors (BSSE) were not corrected, as there is still no sound conclusion how BSSE corrections affect either harmonic frequencies or energies.37,38

Theoretical spectra were generated using Swizard program39,40 by applying an average Gaussian linewidth of 15 cm-1 and harmonic vibrational frequencies were scaled uniformly by a

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factor to be compared with IRPD spectra. The derivation of the scaling factors will be discussed in detail for each specific system in following chapters.

The effective temperatures of our ion clusters are modeled using the Rice-Ramsperger-Kassel-Marcus evaporative ensemble (RRKM-EE) formulism, which is described in detail elsewhere.1,41–43 The RRKM-EE output effective temperatures are corrected by a factor based on the binding energies of argon of different ion clusters.30 The average vibrational energies of the cluster ions are estimated from the ab initio harmonic vibrational frequencies and the RRKM-EE effective temperature, assuming that the energy is equipartitioned using a microcanonical

ensemble.30,31 Gibbs free energies are calculated using the molecular partition function from ab initio vibrational frequencies via thermo.pl PERL script.44

There are two major drawbacks to static ab initio quantum calculations. The first major drawback is the intrinsically applied double harmonic approximations (harmonic electronic potential and harmonic dipole moment surfaces).45 Therefore, vibrational anharmonicities, such as coupling of different vibrational modes, cannot be fully taken into account. Also, the

vibrational frequencies observed in infrared spectra of highly anharmonic vibrational modes cannot be well reproduced using static ab initio calculations. Elaborate theoretical methods for treating anharmonicities have been developed by Gerber and co-workers, computing anharmonic vibrational spectra directly from ab initio surfaces (vibrational SCF, VSCF).46–49 McCoy and co-workers used a reduced dimensional formalism to directly consider the highly anharmonic in- and out-of-plane hydrogen bonded stretches.50 Bowman and collaborators developed Vibrational Configuration Interaction (VCI) method which was applied to ionic H-bonded systems.51 The computational demands for these methods, are somewhat large, especially for systems composed of more than 10 atoms.45 The second major drawback is the inherent 0 K temperature associated

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with the search for the minima on the potential energy surface.45 The explicit introduction of temperature and the related conformational dynamics for vibrational signatures is not as critical at low temperatures. However, in order to reproduce experimental spectra at finite temperatures, i.e. higher than ~100 K, temperature effects and conformational dynamics have to be taken into full account.1,9,11,12,52–54

Molecular Dynamics (MD) simulations at finite temperature can resolve these issues.45 Within the past few years, Gaigeot and co-workers have shown that ab initio molecular dynamics is a useful method for the calculation of IR spectra of hydrated lithium cations,55,56 hydrated amides,57 and other hydrated biomolecules complexes54,58 in the gas phase at finite temperatures. The calculation of infrared spectra through MD relies on dipole moment time correlation functions recorded along the trajectory of atomic motions, which sample the temperature-accessible portions of the potential energy surface. The Fourier transform of this correlation function directly yields infrared frequencies and intensities, free from the double harmonic approximation, as is shown in equation 2.2,45

𝐼(𝜔) = 2𝜋𝛽𝜔_3𝑐𝑉2∫ 𝑑𝑡 < 𝑀(𝑡) ∙ 𝑀(0) > exp(𝑖𝜔𝑡)_−∞∞ (2.2)

where 𝛽 = 1/𝑘𝑇, c is the speed of light in vacuum and V is the volume. The highly anharmonic water-nitrite system will be investigated using Molecular Dynamics simulations at finite

temperatures as an example to illustrate the potential of MD simulations in reproducing

anharmonic intermolecular motions, particularly the vibrational mode coupling between the OH stretch and the rocking motion of the water molecule. We performed DFT-based

Born-Oppenheimer Molecular Dynamics simulations (BOMD) with the CP2K package,59 where the nuclei are treated classically and the electrons quantum mechanically within the DFT formalism.

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Goedecker-Teter-Hutter (GTH) pseudopotentials62,63 is applied. More detailed descriptions about the DFT-MD simulation techniques and its application in the systems of interest are given in Chapter 6.

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2.3 References

(1) Miller, D. J.; Lisy, J. M. Hydrated Alkali-Metal Cations: Infrared Spectroscopy and ab initio Calculations of M+(H2O)x=2−5Ar cluster ions for M = Li, Na, K, and Cs. J. Am. Chem. Soc. 2008, 130, 15381–15392.

(2) Miller, D. J. Elucidating the Hydration of Biomolecules: An Experimental and

Computational Approach.; Doctoral Dissertation, University of Illinois, Urbana-Champaign, 2007.

(3) Beck, J. P. Infrared Spectroscopy of Cluster Ions: High Energy Conformer Trapping and Multiple Photon Absorption; Doctoral Dissertation, University of Illinois, Urbana-Champaign, 2011.

(4) Zwier, T. S. The Spectroscopy of Solvation in Hydrogen-bonded Aromatic Clusters. Annu. Rev. Phys. Chem. 1996, 47, 205–241.

(5) Carney, J. R.; Zwier, T. S. Infrared and Ultraviolet Spectroscopy of Water-Containing Clusters of Indole, 1-Methylindole, and 3-Methylindole. J. Phys. Chem. A. 1999, 103, 9943– 9957.

(6) Chang, T. M.; Chakrabarty, S.; Williams, E. R. Hydration of Gaseous m-Aminobenzoic Acid: Ionic vs Neutral Hydrogen Bonding and Water Bridges. J. Am. Chem. Soc. 2014, 136, 10440– 10449.

(7) Miller, D. J.; Lisy, J. M.Hydration of Ion-biomolecule Complexes: ab initio Calculations and Gas-phase Vibrational Spectroscopy of K+(indole)m(H2O)n. J. Chem. Phys. 2006, 124, 184301. (8) Miller, D. J.; Lisy, J. M. Modeling Competitive Interactions in Proteins: Vibrational Spectroscopy of M+(n-methylacetamide)1(H2O)n=0-3, M = Na and K, in the 3μ Region.J. Phys. Chem. A. 2007, 111, 12409–12416.

(9) Miller, D. J.; Lisy, J. M. Entropic Effects on Hydrated Alkali-Metal Cations: Infrared

Spectroscopy and ab Initio Calculations of M+(H2O)x=2−5 Cluster Ions for M = Li, Na, K, and Cs. J. Am. Chem. Soc. 2008, 130, 15393–15404.

(10) Nicely, A. L.; Miller, D. J.; Lisy, J. M. Gas-phase Vibrational Spectroscopy and ab initio Calculations of Rb+(H2O)n and Rb+(H2O)nAr Cluster Ions. J. Mol. Spectrosc. 2009, 257, 157– 163.

(11) Nicely, A. L.; Miller, D. J.; Lisy, J. M. Charge and Temperature Dependence of

Biomolecule Conformations: K+Tryptamine(H2O)n=0-1Arm=0-1 Cluster Ions. J. Am. Chem. Soc.

2009, 131, 6314–6315.

(12) Nicely, A. L.; Lisy, J. M. Charge and Temperature Effects on Hydrated Tryptamine Cluster Ions. J. Phys. Chem. A. 2011, 115, 2669–2678.

(13) Froese Fischer, C. General Hartree-Fock Program. Comput. Phys. Commun. 1987, 43, 355– 365.

(14) Hoffmann, R. An Extended Hückel Theory. I. Hydrocarbons. J. Chem. Phys. 1963, 39, 1397–1412.

(15) Møller, C.; Plesset, M. S. Note on an Approximation Treatment for Many-Electron Systems. Phys. Rev. 1934, 46, 618–622.

(16) David Sherrill, C.; Schaefer, H. F., III. In Advances in Quantum Chemistry. Per-Olov Löwdin, John R. Sabin Michael C. Zerner and Erkki Brändas, Ed.; Academic Press, 1999; Vol. 34; pp 143–269.

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(18) Si̇nanoğlu, O. Many-Electron Theory of Atoms and Molecules. I. Shells, Electron Pairs vs Many-Electron Correlations. J. Chem. Phys. 1962, 36, 706–717.

(19) Ditchfield, R.; Hehre, W. J.; Pople, J. A. Self-Consistent Molecular-Orbital Methods. IX. An Extended Gaussian-Type Basis for Molecular-Orbital Studies of Organic Molecules. J. Chem. Phys. 1971, 54, 724–728.

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(21) Krishnan, R.; Pople, J. A. Approximate Fourth-order Perturbation Theory of the Electron Correlation Energy. Int. J. Quantum Chem. 1978, 14, 91–100.

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