Solutions of citric acid and Na2HPO4 were studied with the dynamical approach to multiequilibria systems. This widely employed buffer has a well-defined pH profile and allows for the study of the distribution of phosphate species over a wide pH range. The dynamical approach is a flexible and accurate method for the calculation of all species concentrations in multiequilibria considering ionic strength (I) via Debye–Hückel theory. The agreement between the computed pH profiles and experiment is excellent. The equilibrium concentrations of the non-hydrogen species are reported for over 30 buffer mixtures across the entire pH range. These new concentration data enable researchers to lookup the equilibrium distribution of species at any pH. The data highlight the dramatic effects of ionic strength, and for example, the position of maximal H2PO4 – concentration is shifted by almost an entire pH unit! From a more general perspective, the study allows for a discussion of the dependence of concentration quotients Q xy on ionic strength, pQ xy = f(I), and for the numerical demonstration that the thermodynamic equilibrium constants K xy,act(I) = K xy . The analysis emphasizes the need for measurements of the concentrations of several species in complex multiequilibria systems over a broad pH range to advance multiequilibria simulations.

No abstract

In theoretical studies of chemical reactions the reaction thermochemistry is usually reported for the stoichiometric reaction at standard conditions (∆G˝, ∆H˝, ∆S˝). We describe the computation of the equilibrium concentrations of the CO 2-adducts for the general capture reaction CO 2 + Capture System Õ CO 2-adduct (GCR) and the rubisco-type capture reaction CO 2 + Capture System Õ CO 2-adduct + H 2 O (RCR) with consideration of the reaction CO 2 (g) Õ CO 2 (aq) via Henry's law. The resulting equations are evaluated and graphically illustrated as a function of atmospheric CO 2 concentration and as a function of temperature. The equations were applied to the thermochemistry of small molecule rubisco-model reactions and series of additional model reactions to illustrate the range of the Gibbs free enthalpy for the effective reversible capture and of the reaction entropy for economic CO 2 release at elevated temperature. A favorable capture of free enthalpy is of course a design necessity, but not all exergonic reactions are suitable CO 2 capture systems. Successful CO 2 capture systems must allow for effective release as well, and this feature is controlled by the reaction entropy. The principle of using a two-pronged capture system to ensure a large negative capture entropy is explained and highlighted in the graphical abstract. It is hoped that the presentation of the numerical examples provides useful guidelines for the design of more efficient capture systems.

We have been interested in the development of rubisco-based biomimetic systems for reversible CO 2 capture from air. Our design of the chemical CO 2 capture and release (CCR) system is informed by the understanding of the binding of the activator CO 2 ( A CO 2 ) in rubisco (ribulose-1,5-bisphosphate carboxylase/ oxygenase). The active site consists of the tetrapeptide sequence Lys-Asp-Asp-Glu (or KDDE) and the Lys sidechain amine is responsible for the CO 2 capture reaction. We are studying the structural chemistry and the thermodynamics of CO 2 capture based on the tetrapeptide CH 3 COÀ KDDEÀ NH 2 ("KDDE") in aqueous solution to develop rubisco mimetic CCR systems. Here, we report the results of 1 H NMR and 13 C NMR analyses of CO 2 capture by butylamine and by KDDE. The carbamylation of butylamine was studied to develop the NMR method and with the protocol established, we were able to quantify the oligopeptide carbamylation at much lower concentration. We performed a pH profile in the multi equilibrium system and measured amine species and carbamic acid/ carbamate species by the integration of 1 H NMR signals as a function of pH in the range 8 � pH � 11. The determination of ΔG 1 (R) for the reaction RÀ NH 2 + CO 2 !RÀ NHÀ COOH requires the solution of a multi-equilibrium equation system, which accounts for the dissociation constants K 2 and K 3 controlling carbonate and bicarbonate concentrations, the acid dissociation constant K 4 of the conjugated acid of the amine, and the acid dissociation constant K 5 of the alkylcarbamic acid. We show how the multi-equilibrium equation system can be solved with the measurements of the daughter/parent ratio X, the knowledge of the pH values, and the initial concentrations [HCO 3 À ] 0 and [R-NH 2 ] 0 . For the reaction energies of the carbamylations of butylamine and KDDE, our best values are ΔG 1 (Bu) = À 1.57 kcal/mol and ΔG 1 (KDDE) = À 1.17 kcal/mol. Both CO 2 capture reactions are modestly exergonic and thereby ensure reversibility in an energy-efficient manner. These results validate the hypothesis that KDDE-type oligopeptides may serve as reversible CCR systems in aqueous solution and guide designs for their improvement.

Rubisco is the enzyme responsible for CO 2 fixation in nature, and it is activated by CO 2 addition to the amine group of its lysine 201 side chain. We are designing rubisco-based biomimetic systems for reversible CO 2 capture from ambient air. The oligopeptide biomimetic capture systems are employed in aqueous solution. To provide a solid foundation for the experimental solution-phase studies of the CO 2 capture reaction, we report here the results of computational studies of the thermodynamics of CO 2 capture by small alkylamines in aqueous solution. We studied CO 2 addition to methyl-, ethyl-, propyl-, and butylamine with the consideration of the full conformational space for the amine and the corresponding carbamic acids and with the application of an accurate solvation model for the potential energy surface analyses. The reaction energies of the carbamylation reactions were determined based on just the most stable structures (MSS) and based on the ensemble energies computed with the Boltzmann distribution (BD), and it is found that ΔG BD ≈ ΔG MSS . The effect of the proper accounting for the molecular translational entropies in solution with the Wertz approach are much more significant, and the free energy of the capture reactions Δ W G BD is more negative by 2.9 kcal/mol. Further accounting for volume effects in solution results in our best estimates for the reaction energies of the carbamylation reactions of Δ W A BD = −5.4 kcal/mol. The overall difference is ΔG BD − Δ W A BD = 2.4 kcal/mol for butylamine carbamylation. The full conformational space analyses inform about the conformational isomerizations of carbamic acids, and we determined the relevant rotational profiles and their transition-state structures. Our detailed studies emphasize that, more generally, solution-phase reaction energies should be evaluated with the Helmholtz free energy and can be affected substantially by solution effects on translational entropies.

Equilibrium is a key theme in chemistry education. Starting in high school and continuing in freshman general chemistry courses, STEM students have to learn the foundations of equilibria. What is the key concept of an equilibrium? How can we describe an equilibrium? The concept of an equilibrium constant K is introduced, and its relation to the Gibbs enthalpy [delta] G [superscript 0] is noted. The equilibrium constant K also is related in a straightforward manner to the forward and backward reaction rate constants. Usually, a few simple applications are discussed, primarily in the area of acid-base chemistry. The topic is revisited in organic chemistry and clarified conceptually with reaction energy diagrams. To study equilibrium as a student is one thing, and to study equilibrium problems as a researcher is quite another. How does one determine equilibrium constants and how does one determine reaction rate constants? What do we know about the accuracy of the experimental quantities reported in the literature? How does one deal with multi-equilibria? How does one account for non-ideal conditions and concentrated solutions? Over the last six years, I have learned how to approach and solve all of these issues. One of the most stunning insights was the realization that even so-called non-linear reactions can in fact be described in some cases by application of complicated systems of equilibrium reactions. The Glaser group very strongly believes that the interplay between experimental and theoretical work is vitally important to really understand a problem. This combination builds a strong focus on quantitative aspects and it often also leads to new insights that might not be attainable from experimentation or modeling alone. The five chapters presented here show that this two-pronged approach is widely applicable to several areas of chemistry. The two main topics of our studies have been carbon dioxide capture from air and reaction mechanisms of oscillating chemical systems. All of the chapters in my dissertation do have a very strong connection between theory and experimentation. I studied both aspects in most cases. Only in one case (Chapter 5) did I not perform the experiments, but even in this case, a very deep engagement with the experimental literature was required to solve a decades-long discrepancy. Chapter 1 is about the study of equilibria between different conformations of substrates and products and an evaluation of their effects on the overall reaction energy. Specifically, we studied the capture of CO2 by small alkylamines. The quality of that discussion was tested directly with the work described in Chapter 2. The work that led to Chapter 2 was an enormous learning experience; it was amazing to see all the pieces of the complicated multi-equilibrium system come together to determine the [delta] G [superscript 0] of the carbamylation of butylamine in aqueous solution. The interest in equilibria actually began with the quest of the non-linear dynamics group to understand oscillating chemical reactions. From the outset, this quest was pursued as an interdisciplinary project between chemistry and mathematics. My work with the dynamics group resulted in Chapters 3 and 4 of the present dissertation. Chapter 3 is a re-evaluation of the video-based kinetic analysis with high temporal resolution and over long timescales. The colorimetric studies revealed unexpected "hysteresis loops" in cerium-catalyzed Belousov-Zhabotinsky oscillating reactions. We studied the reaction progress in RGB space because we wanted to learn under what conditions the video-based analysis would allow for quantitative concentration determinations. The desire to assess the quality of the video-based analysis in RGB space, led to the serendipitous discovery of hysteresis loops. The origins of Chapter 4 had to do with the question as to whether accounting for ionic strength would be essential to obtain accurate simulations of BZ reactions. The goal of my work on phosphate buffers was an evaluation of the usefulness of Debye-Huckel theory to electrolyte solutions with highly-charged ions present in significant concentrations. The phosphate buffer systems are widely in use and outstanding experimental sets of pH values were available to really test the performance of the solution models. Many years of studies of the Lewis acid-base pair F3B[arrow]PH3 illustrate in a beautiful fashion what can go wrong when expertalists interpret their data based on inaccurate theory and when computational chemists do not seek consistency with existing experimental data published in the literature. A careful read of the literature clearly showed early on that experimental and theoretical reports on F3B[arrow]PH3 are entirely inconsistent. It took years to explain what was actually measured, namely the compound F2B-PH2, and to explain why many theoretical reports predicted the wrong dative-bonding geometry.

The loss and/or dysregulation of several cellular and mitochondrial antioxidants’ expression or enzymatic activity, which leads to the aberrant physiological function of these proteins, has been shown to result in oxidative damage to cellular macromolecules. In this regard, it has been surmised that the disruption of mitochondrial networks responsible for maintaining normal metabolism is an established hallmark of cancer and a novel mechanism of therapy resistance. This altered metabolism leads to aberrant accumulation of reactive oxygen species (ROS), which, under specific physiological conditions, leads to a potential tumor-permissive cellular environment. In this regard, it is becoming increasingly clear that the loss or disruption of mitochondrial oxidant scavenging enzymes may be, in specific tumors, either an early event in transformation or exhibit tumor-promoting properties. One example of such an antioxidant enzyme is manganese superoxide dismutase (MnSOD, also referred to as SOD2), which detoxifies superoxide, a ROS that has been shown, when its normal physiological levels are disrupted, to lead to oncogenicity and therapy resistance. Here, we will also discuss how the acetylation of MnSOD leads to a change in detoxification function that leads to a cellular environment permissive for the development of lineage plasticity-like properties that may be one mechanism leading to tumorigenic and therapy-resistant phenotypes.

No abstract