Raghunath O. Ramabhadran

Aromatic and Aliphatic CH Hydrogen Bonds Fight for Chloride while Competing Alongside Ion Pairing within Triazolophanes

Triazolophanes are used as the venue to compete an aliphatic propylene CH hydrogen-bond donor against an aromatic phenylene one. Longer aliphatic C-H...Cl(-) hydrogen bonds were calculated from the location of the chloride within the propylene-based triazolophane. The gas-phase energetics of chloride binding (ΔG(bind) , ΔH(bind) , ΔS(bind) ) and the configurational entropy (ΔS(config) ) were computed by taking all low-energy conformations into account. Comparison between the phenylene- and propylene-based triazolophanes shows the computed gas-phase free energy of binding decreased from ΔG(bind) =-194 to -182 kJ mol(-1) , respectively, with a modest enthalpy-entropy compensation. These differences were investigated experimentally. An (1) H NMR spectroscopy study on the structure of the propylene triazolophanes 1:1 chloride complex is consistent with a weaker propylene CH hydrogen bond. To quantify the affinity differences between the two triazolophanes in dichloromethane, it was critical to obtain an accurate binding model. Four equilibria were identified. In addition to 1:1 complexation and 2:1 sandwich formation, ion pairing of the tetrabutylammonium chloride salt (TBA(+) ⋅Cl(-) ) and cation pairing of TBA(+) with the 1:1 triazolophane-chloride complex were observed and quantified. Each complex was independently verified by ESI-MS or diffusion NMR spectroscopy. With ion pairing deconvoluted from the chloride-receptor binding, equilibrium constants were determined by using (1) H NMR (500 μM) and UV/Vis (50 μM) spectroscopy titrations. The stabilities of the 1:1 complexes for the phenylene and propylene triazolophanes did not differ within experimental error, ΔG=(-38±2) and (-39±1) kJ mol(-1) , respectively, as verified by an NMR spectroscopy competition experiment. Thus, the aliphatic CH donor only revealed its weaker character when competing with aromatic CH donors within the propylene-based triazolophane.

An Overlooked yet Ubiquitous Fluoride Congenitor: Binding Bifluoride in Triazolophanes Using Computer-Aided Design

Despite its ubiquity during the binding and sensing of fluoride, the role of bifluoride (HF2(-)) and its binding properties are almost always overlooked. Here, we give one of the first examinations of bifluoride recognition in which we use computer-aided design to modify the cavity shape of triazolophanes to better match with HF2(-). Computational investigation indicates that HF2(-) and Cl(-) should have similar binding affinities to the parent triazolophane in the gas phase. Evaluation of the binding geometries revealed a preference for binding of the linear HF2(-) along the north-south axis with a smaller Boltzmann weighted population aligned east-west and all states being accessed rapidly through in-plane precessional rotations of the anion. While the (1)H NMR spectroscopy studies are consistent with the calculated structural aspects, binding affinities in solution were determined to be significantly smaller for the bifluoride than the chloride. Computed geometries suggested that a 20° tilting of the bifluoride (stemming from the cavity size) could account for the 25-fold difference between the two binding affinities, HF2(-) < Cl(-). Structural variations to the triazolophanes geometry and electronic modifications to the network of hydrogen bond donors were subsequently screened in a stepwise manner using density functional theory calculations to yield a final design that eliminates the tilting. Correspondingly, the bifluorides binding affinity (K ∼ 10(6) M(-1)) increased and was also found to remain equal to chloride in the gas and solution phases. The new oblate cavity appeared to hold the HF2(-) in a single east-west arrangement. Our findings demonstrate the promising ability of computer-aided design to fine-tune the structural and electronic match in anion receptors as a means to control the arrangement and binding strength of a desired guest.

New insights on photocatalytic H2 liberation from water using transition-metal oxides: lessons from cluster models of molybdenum and tungsten oxides.

Molecular hydrogen (H2) is an excellent alternative fuel. It can be produced from the abundantly present water on earth. Transition-metal oxides are widely used in the environmentally benign photocatalytic generation of H2 from water, thus actively driving scientific research on the mechanisms for this process. In this study, we investigate the chemical reactions of W3O5(-) and Mo3O5(-) clusters with water that shed light on a variety of key factors central to H2 generation. Our computational results explain why experimentally Mo3O5(-) forms a unique kinetic trap in its reaction while W3O5(-) undergoes a facile oxidation to form the lowest-energy isomer of W3O6(-) and liberates H2. Mechanistic insights on the reaction pathways that occur, as well as the reaction pathways that do not occur, are found to be of immense assistance to comprehend the hitherto poorly understood pivotal roles of (a) differing metal-oxygen and metal-hydrogen bond strengths, (b) the initial electrostatic complex formed, (c) the loss of entropy when these TMO clusters react with water, and (d) the geometric factors involved in the liberation of H2.

Connectivity-Based Hierarchy for theoretical thermochemistry: assessment using wave function-based methods.

The Connectivity-Based Hierarchy (CBH) is a generalized method we have developed recently to accurately predict the thermochemical properties of large closed-shell organic molecules-hydrocarbons as well as nonhydrocarbons. The performance of the different rungs of the hierarchy was initially evaluated using density functional theory. In this study, we have carried out a wave function-based analysis of the CBH method to analyze the influence of electron correlation effects on the reaction energies and enthalpies of formation. For a test set containing unstrained molecules, all levels of theory (HF, MP2, and CCSD(T)) yield small reaction energies and accurate enthalpies of formation even with modest-sized polarized double-ζ or triple-ζ basis sets. For an initial test set of five strained molecules, however, the computed reaction energies are not small, though correlated schemes still yield accurate enthalpies of formation. Thus, small reaction energies cannot be used as the principal criterion to calibrate the success of thermochemical reaction schemes for molecules possessing special features (such as ring strain or aromaticity). Overall, for the relatively large nonaromatic molecules considered in this study, the mean absolute deviation with the MP2 method at the isoatomic CBH-2 rung is comparable to that with the more expensive CCSD(T) method at the higher CBH-3 rung.

Extrapolation to the Gold-Standard in Quantum Chemistry: Computationally Efficient and Accurate CCSD(T) Energies for Large Molecules Using an Automated Thermochemical Hierarchy

The CCSD(T) method is known as the gold-standard in quantum chemistry and has been the method of choice in quantum chemistry for over 20 years to obtain accurate bond energies and molecular properties. Its computational cost formally scales as the seventh power of the size of the system and can be prohibitive for large molecules. As part of our efforts to reduce the computational cost of the CCSD(T) method yet retain its accuracy, we present a simple, efficient, and user-friendly protocol to extrapolate to CCSD(T) energies in conjunction with MP2 energies. The method is based on the automated error-canceling thermochemical hierarchy previously developed by us called the Connectivity-Based Hierarchy (CBH). For a test set containing 30 diverse nonaromatic organic molecules and biomonomers, we obtain highly accurate extrapolated CCSD(T) energies (with a mean absolute error of only 0.2-0.3 kcal/mol with different basis-set). Additionally, the work also features the successful extrapolation to CCSD energies using a similar protocol.

C vs N: Which End of the Cyanide Anion Is a Better Hydrogen Bond Acceptor?

The ability of the C and N ends of the cyanide anion (CN(-)) as acceptors of hydrogen bonds, an experimentally difficult problem, has been computationally examined in this study. Structures obtained in our previous work involving cyanide binding within the cavity of a triazolophane macrocycle (Chem.-Eur. J. 2011, 17, 9123-9129) were used to analyze the problem. Three different approaches involving (a) breakdown of the triazolophane into smaller components, (b) population analyses, and (c) ion-dipole analyses helped demonstrate that the N terminus of cyanide is a slightly better hydrogen bond acceptor than the C terminus even though it is not the site of protonation or covalent bond formation. This outcome reflects a competition between the preference for noncovalent interactions at the nitrogen and covalent bond formation at the carbon.

Application of the generalized connectivity-based hierarchy to biomonomers: enthalpies of formation of cysteine and methionine.

Computational challenges toward an accurate determination of the enthalpies of formation of amino acids are partly due to the nonavailability of systematic error-canceling thermochemical procedures for such biomonomers. Recently, we developed the connectivity-based hierarchy (CBH) to accurately compute the enthalpies of formations of organic molecules composed of main group elements. Advancing the applicability of CBH to biologically relevant molecules, we have computed the enthalpies of formation of the naturally occurring sulfur-containing amino acids cysteine and methionine which act as fertile testing grounds for the error-canceling ability of thermochemical schemes for biomolecules. We establish herein using the sophisticated error-canceling isoatomic scheme (CBH-2) that relatively inexpensive computational methods with modest basis sets can be used to accurately obtain the enthalpies of formations of the amino acids. Overall, we recommend the use of the isoatomic scheme over the currently popular isodesmic bond separation scheme in future applications in theoretical thermochemistry.

The successful merger of theoretical thermochemistry with fragment-based methods in quantum chemistry.

CONSPECTUS: Quantum chemistry and electronic structure theory have proven to be essential tools to the experimental chemist, in terms of both a priori predictions that pave the way for designing new experiments and rationalizing experimental observations a posteriori. Translating the well-established success of electronic structure theory in obtaining the structures and energies of small chemical systems to increasingly larger molecules is an exciting and ongoing central theme of research in quantum chemistry. However, the prohibitive computational scaling of highly accurate ab initio electronic structure methods poses a fundamental challenge to this research endeavor. This scenario necessitates an indirect fragment-based approach wherein a large molecule is divided into small fragments and is subsequently reassembled to compute its energy accurately. In our quest to further reduce the computational expense associated with the fragment-based methods and overall enhance the applicability of electronic structure methods to large molecules, we realized that the broad ideas involved in a different area, theoretical thermochemistry, are transferable to the area of fragment-based methods. This Account focuses on the effective merger of these two disparate frontiers in quantum chemistry and how new concepts inspired by theoretical thermochemistry significantly reduce the total number of electronic structure calculations needed to be performed as part of a fragment-based method without any appreciable loss of accuracy. Throughout, the generalized connectivity based hierarchy (CBH), which we developed to solve a long-standing problem in theoretical thermochemistry, serves as the linchpin in this merger. The accuracy of our method is based on two strong foundations: (a) the apt utilization of systematic and sophisticated error-canceling schemes via CBH that result in an optimal cutting scheme at any given level of fragmentation and (b) the use of a less expensive second layer of electronic structure method to recover all the missing long-range interactions in the parent large molecule. Overall, the work featured here dramatically decreases the computational expense and empowers the execution of very accurate ab initio calculations (gold-standard CCSD(T)) on large molecules and thereby facilitates sophisticated electronic structure applications to a wide range of important chemical problems.

Fluxionality in the chemical reactions of transition metal oxide clusters: the role of metal, spin state, and the reactant molecule.

The phenomenon of fluxionality in the reactions of transition metal oxide clusters provides many opportunities in various catalytic and industrial processes. To gain a better understanding into the various factors influencing this phenomenon, we have carried out an electronic structure investigation of the fluxionality pathways when W(3)O(6)(-) and Mo(3)O(6)(-) clusters react with hydrogen sulfide and ammonia. The study illustrates how the metal (W vs Mo), different spin states of the anionic metal oxide cluster (doublet vs quartet), and the nature of the nonmetal in the small molecule (O vs S vs N), all affect the fluxionality pathway. The thermodynamically facile fluxionality pathway with H(2)S detaches both the hydrogens from hydrogen sulfide and can thus be very useful in the petrochemical and desulfurization industries. The fluxionality pathway with NH(3) results in interesting metal-bound imines and bridged amines. However, the overall fluxionality process with NH(3) is found to be thermodynamically unfavorable.

Accurate and computationally efficient prediction of thermochemical properties of biomolecules using the generalized connectivity-based hierarchy.

In this study we have used the connectivity-based hierarchy (CBH) method to derive accurate heats of formation of a range of biomolecules, 18 amino acids and 10 barbituric acid/uracil derivatives. The hierarchy is based on the connectivity of the different atoms in a large molecule. It results in error-cancellation reaction schemes that are automated, general, and can be readily used for a broad range of organic molecules and biomolecules. Herein, we first locate stable conformational and tautomeric forms of these biomolecules using an accurate level of theory (viz. CCSD(T)/6-311++G(3df,2p)). Subsequently, the heats of formation of the amino acids are evaluated using the CBH-1 and CBH-2 schemes and routinely employed density functionals or wave function-based methods. The calculated heats of formation obtained herein using modest levels of theory and are in very good agreement with those obtained using more expensive W1-F12 and W2-F12 methods on amino acids and G3 results on barbituric acid derivatives. Overall, the present study (a) highlights the small effect of including multiple conformers in determining the heats of formation of biomolecules and (b) in concurrence with previous CBH studies, proves that use of the more effective error-cancelling isoatomic scheme (CBH-2) results in more accurate heats of formation with modestly sized basis sets along with common density functionals or wave function-based methods.