Annual Review of Physical Chemistry - Volume 62, 2011

This is an account mostly of what I have seen and worked on in physical chemistry, from my time in graduate school six decades ago to the present. It is a personal story about kinetics, thermodynamics, and statistical mechanics—in which subjects I continue to be educated, thanks to patient instruction by my students and associates.

When I had the invitation from Steve Leone to write this article I said “yes” because (a) “yes” is my default setting; (b) it was a great honor to have been invited to do it; and (c) I was too busy at the time to think about what the consequences of saying “yes” would be. I must now do my best to fulfill my promise.

The photochemically induced electrocyclic ring-opening reaction of 1,3-cyclohexadiene to 1,3,5-hexatriene serves as a prototype for many important reactions in chemistry and in biological systems. Based on experimental and computational studies, a detailed picture of the reaction has now emerged: Excitation to the Franck-Condon region places the molecule on a steeply repulsive part of the 1B potential energy surface, which propels the molecule in exactly the conrotatory direction that conforms to the Woodward-Hoffmann rules of orbital symmetry. Bypassing a cusp in a symmetry-breaking direction, the wave packet enters the 2A state within 55 fs. It continues to move directly toward the 2A/1A conical intersection, where it crosses in approximately 80 fs to the ground state. This article summarizes the published experimental and theoretical work to describe the current understanding of the reaction while pointing to important questions that remain to be addressed.

Recent years have witnessed an explosion in computational power, leading to attempts to model ever more complex systems. Nevertheless, there remain cases for which the use of brute-force computer simulations is clearly not the solution. In such cases, great benefit can be obtained from the use of physically sound simplifications. The introduction of such coarse graining can be traced back to the early usage of a simplified model in studies of proteins. Since then, the field has progressed tremendously. In this review, we cover both key developments in the field and potential future directions. Additionally, particular emphasis is given to two general approaches, namely the renormalization and reference potential approaches, which allow one to move back and forth between the coarse-grained (CG) and full models, as these approaches provide the foundation for CG modeling of complex systems.

Near their glass transition temperature Tg, supercooled liquids display dramatic changes regarding the dynamics if subject to geometrical restrictions on the scale of 2 to 200 nm. Confinement-induced shifts of Tg of 25 K have been reported, equivalent to relaxation times that differ by several orders of magnitude compared with the bulk liquid at the same temperature. Both acceleration and frustration of structural relaxations have been observed, and the effects can depend strongly on the physical and chemical properties of the interface, on soft versus hard confinement, and on the size and dimensionality of the confining topology. This review attempts to extract a unifying picture from the past 20 years of diverse observations that involve experiments, simulations, and model considerations.

Ionic liquids are subjects of intense current interest within the physical chemistry community. A great deal of progress has been made in just the past five years toward identifying the factors that cause these salts to have low melting points and other useful properties. Supramolecular structure and organization have emerged as important and complicated topics that may be key to understanding how chemical reactions and other processes are affected by ionic liquids. New questions are posed, and an active debate is ongoing regarding the nature of nanoscale ordering in ionic liquids. The topic of reactivity in ionic liquids is still relatively unexplored; however, the results that have been obtained indicate that distributed kinetics and dynamical heterogeneity may sometimes, but not always, be influencing factors.

Although this review provides references to tabulations of molecular electron affinities, primarily it focuses on explaining why theory plays an important role in understanding the behavior of anions, explaining the challenges that anions pose to theory, making connections between the theories used to compute electron affinities and the potentials (e.g., charge-dipole, charge-quadrupole, valence attraction and exchange repulsion, dispersion, and polarization) that govern the electron-molecule interaction, and discussing how species with negative electron affinities may possess metastable anion states and how such states should be treated. In addition to references to published literature, many links are given to websites of practicing theoretical chemists who study molecular anions; these links (which appear in boldface) offer the reader a broad avenue to access much more information about molecular anions than can be covered in a review or even through conventional literature sources.

From exponentially large numbers of possible sequences, protein design seeks to identify the properties of those that fold to predetermined structures and have targeted structural and functional properties. The interactions that confer structure and function involve intermolecular forces and large numbers of interacting amino acids. As a result, the identification of sequences can be subtle and complex. Sophisticated methods for characterizing sequences consistent with a particular structure have been developed, assisting the design of novel proteins. Developments in such computational protein design are discussed, along with recent accomplishments, ranging from the redesign of existing proteins to the design of new functionalities and nonbiological applications.

Recent developments allow heat capacities to be measured for size-selected clusters isolated in the gas phase. For clusters with tens to hundreds of atoms, the heat capacities determined as a function of temperature usually have a single peak attributed to a melting transition. The melting temperatures and latent heats show large size-dependent fluctuations. In some cases, the melting temperatures change by hundreds of degrees with the addition of a single atom. Theory has played a critical role in understanding the origin of the size-dependent fluctuations, and in understanding the properties of the liquid-like and solid-like states. In some cases, the heat capacities have extra features (an additional peak or a dip) that reveal a more complex behavior than simple melting. In this article we provide a description of the methods used to measure the heat capacities and provide an overview of the experimental and theoretical results obtained for sodium and aluminum clusters.

The discovery of polar polyatomic molecules in higher-density regions of the interstellar medium by means of their rotational emission detected by radioastronomy has changed our conception of the universe from essentially atomic to highly molecular. We discuss models for molecule formation, emphasizing the general lack of thermodynamic equilibrium. Detailed chemical kinetics is needed to understand molecule formation as well as destruction. Ion molecule reactions appear to be an important class for the generally low temperatures of the interstellar medium. The need for the intrinsically high-quality factor of rotational transitions to definitively pin down molecular emitters has been well established by radioastronomy. The observation of abundant molecular ions both positive and, as recently observed, negative provides benchmarks for chemical kinetic schemes. Of considerable importance in guiding our understanding of astronomical chemistry is the fact that the larger molecules (with more than five atoms) are all organic.

The difficulty of simulating quantum systems, well known to quantum chemists, prompted the idea of quantum computation. One can avoid the steep scaling associated with the exact simulation of increasingly large quantum systems on conventional computers, by mapping the quantum system to another, more controllable one. In this review, we discuss to what extent the ideas in quantum computation, now a well-established field, have been applied to chemical problems. We describe algorithms that achieve significant advantages for the electronic-structure problem, the simulation of chemical dynamics, protein folding, and other tasks. Although theory is still ahead of experiment, we outline recent advances that have led to the first chemical calculations on small quantum information processors.

Multiresonant coherent multidimensional spectroscopy is a frequency-domain method that uses tunable excitation pulses to excite multiple quantum coherences (MQCs) and/or state populations using fully coherent or partially coherent excitation pathways. Pairs of states that are coupled by intra- and intermolecular interactions re-emit light at their frequency differences. The MQCs are coherent and interfere constructively to create phase-matched output beams. Scanning the excitation frequencies with fixed-excitation-pulse time delays creates multidimensional spectra, whereas scanning the time delays with fixed excitation frequencies measures the MQCs’ coherent and incoherent dynamics. Multiresonant methods can excite any combination of vibrational and/or electronic states and use any coherence pathway. Cross-peaks occur between states when the excitation of one perturbs the other. This requirement for coupling acts to eliminate spectral congestion. Spectral resolution is increased because multiresonant methods narrow inhomogeneous broadening, enhance peaks from specific components, and spread the resolution over multiple dimensions.

Many aspects of protein folding can be understood in terms of projections of the highly dimensional energy landscape onto a few (or even only one) particularly relevant coordinates. These free-energy surfaces can be probed conveniently from experimental differential scanning calorimetry (DSC) thermograms, as DSC provides a direct relation with the protein partition function. Free-energy surfaces thus obtained are consistent with two fundamental scenarios predicted by the energy-landscape perspective: (a) well-defined macrostates separated by significant free-energy barriers, in some cases, and, in many other cases, (b) marginal or even vanishingly small barriers, which furthermore show a good correlation with kinetics for fast- and ultrafast-folding proteins. Overall, the potential of DSC to assess free-energy surfaces for a wide variety of proteins makes it possible to address fundamental issues, such as the molecular basis of the barrier modulations produced by natural selection in response to functional requirements or to ensure kinetic stability.

Protein stability often is studied in vitro through the use of urea and guanidinium chloride, chemical cosolvents that disrupt protein native structure. Much controversy still surrounds the underlying mechanism by which these molecules denature proteins. Here we review current thinking on various aspects of chemical denaturation. We begin by discussing classic models of protein folding and how the effects of denaturants may fit into this picture through their modulation of the collapse, or coil-globule transition, which typically precedes folding. Subsequently, we examine recent molecular dynamics simulations that have shed new light on the possible microscopic origins of the solvation effects brought on by denaturants. It seems likely that both denaturants operate by facilitating solvation of hydrophobic regions of proteins. Finally, we present recent single-molecule fluorescence studies of denatured proteins, the analysis of which corroborates the role of denaturants in shifting the equilibrium of the coil-globule transition.

Current interest in amyloid fibrils stems from their involvement in neurodegenerative and other diseases and from their role as an alternative structural state for many peptides and proteins. Solid-state nuclear magnetic resonance (NMR) methods have the unique capability of providing detailed structural constraints for amyloid fibrils, sufficient for the development of full molecular models. In this article, recent progress in the application of solid-state NMR to fibrils associated with Alzheimer's disease, prion fibrils, and related systems is reviewed, along with relevant developments in solid-state NMR techniques and technology.

Coarse-grained, self-contained polymer models are powerful tools in the study of protein folding. They are also essential to assess predictions from less rigorous theoretical approaches that lack an explicit-chain representation. Here we review advances in coarse-grained modeling of cooperative protein folding, noting in particular that the Levinthal paradox was raised in response to the experimental discovery of two-state-like folding in the late 1960s, rather than to the problem of conformational search per se. Comparisons between theory and experiment indicate a prominent role of desolvation barriers in cooperative folding, which likely emerges generally from a coupling between local conformational preferences and nonlocal packing interactions. Many of these principles have been elucidated by native-centric models, wherein nonnative interactions may be treated perturbatively. We discuss these developments as well as recent applications of coarse-grained chain modeling to knotted proteins and to intrinsically disordered proteins.

The nature of acids in an aqueous environment is fundamental to many aspects of chemistry. The defining feature of an acid is its ability to transfer a proton to water, but this seemingly simple process can be complex and highly dependent on solvation. This review describes studies aimed at obtaining molecular-level descriptions of acid-water interactions through the study of neutral acid-water complexes. Current understanding of the nature of hydrated protons is first summarized, and a parallel discussion of structural aspects of acid-water complexes is then presented. The nature of proton transfer, and its evolution with cluster size, is described. The review concludes with several examples that lie at the intersection between fundamental work on hydrated acids and important physiochemical processes in the atmosphere.

Laboratory studies of gas-phase chemical processes are a key tool in understanding the chemistry of our atmosphere and hence tackling issues such as climate change and air quality. Laboratory techniques have improved considerably with greater emphasis on product detection, allowing the measurement of site-specific rate coefficients. Radical chemistry lies at the heart of atmospheric chemistry. In this review we consider issues around radical generation and recycling from the oxidation of isoprene and from the chemical reactions and photolysis of carbonyl species. Isoprene is the most globally significant hydrocarbon, but uncertainties exist about its oxidation in unpolluted environments. Recent experiments and calculations that cast light on radical generation are reviewed. Carbonyl compounds are the dominant first-generation products from hydrocarbon oxidation. Chemical oxidation can recycle radicals, or photolysis can be a net radical source. Studies have demonstrated that high-resolution and temperature-dependent studies are important for some significant species.

Beryllium clusters provide an ideal series for exploring the evolution from discrete molecules to the metallic state. The beryllium dimer has a formal bond order of zero, but the molecule is weakly bound. In contrast, bulk-phase beryllium is a hard metal with a high melting point. Theoretical calculations indicate that the bond energies increase dramatically for Ben clusters in the range n=2–6. A triplet ground state is found for n=6, indicating an early emergence of metallic properties. There is an extensive body of theoretical work on smaller Ben clusters, in part because this light element can be treated using high-level methods. However, the apparent simplicity of beryllium is deceptive, and the calculations have proved to be challenging owing to strong electron correlation and configuration interaction effects. Consequently, these clusters have become benchmark systems for the evaluation of a wide spectrum of quantum chemistry methods.

The reorientation of a water molecule is important for a host of phenomena, ranging over—in an only partial listing—the key dynamic hydrogen-bond network restructuring of water itself, aqueous solution chemical reaction mechanisms and rates, ion transport in aqueous solution and membranes, protein folding, and enzymatic activity. This review focuses on water reorientation and related dynamics in pure water, and for aqueous solutes with hydrophobic, hydrophilic, and amphiphilic character, ranging from tetra-methylurea to halide ions and amino acids. Attention is given to the application of theory, simulation, and experiment in the probing of these dynamics, in usefully describing them, and in assessing the description. Special emphasis is placed on a novel sudden, large-amplitude jump mechanism for water reorientation, which contrasts with the commonly assumed Debye rotational diffusion mechanism, characterized by small-amplitude angular motion. Some open questions and directions for further research are also discussed.