Scientific Publications 2010
2010. "Solid-State 55Mn NMR Spectroscopy of bis(μ-oxo)dimanganese(IV) [Mn2O2(salpn)2], a Model for the Oxygen Evolving Complex in Photosystem II." Journal of the American Chemical Society 132(47):16727-16729. doi:10.1021/ja1054252 Abstract Given the obvious global energy needs, it has become imperative to develop a catalytic process for converting water to molecular oxygen and protons. Many have sought to understand the details of photosynthesis and in particular the water splitting reaction to help in the development of the appropriate catalysis.1-3 While the scientific community has made great strides towards this goal, it has fallen short at the critical stage of the determination of the structure associated with the oxygen evolving complex (OEC) within photosystem II (PSII).4,5 Despite the existence of x-ray structures of PSII,6-8 the best data we have for the structure of the OEC comes from models derived from EPR and EXAFS measurements.9-14 This experimental situation has led to collaborations with theoreticians to enable the development of models for the structure of the OEC where the experimental observables (EXAFS and magnetic resonance parameters) serve as constraints to the theoretical calculations. Of particular interest to this study is the observation of the S1 state of the Kok cycle15 where the core of the OEC can be described as a tetranuclear manganese cluster composed of Mn4OxCa. The simplest model for the OEC can be thought of as two Mn-pairs and a Ca2+ where each Mn-pair is antiferromagnetically coupled to its partner. We utilize the term "pair" to describe the Mn atoms within the OEC with the same oxidation state, which for the S1 state is (Mn2(III, III) and Mn2(IV, IV)).16 It is unclear as to the degree of interaction between the pairs as well as the role of the Ca2+. At cryogenic temperatures the S1 state of the OEC is diamagnetic and in principle amenable to solid-state NMR experiments.
2010. "Atomistic Details of the Associative Phosphodiester Cleavage in Human Ribonuclease H." Physical Chemistry Chemical Physics. PCCP 12(36):11081-11088. doi:10.1039/c001097a Abstract During translation of the genetic information of DNA into proteins, mRNA is synthesized by RNA polymerase and after the transcription process degraded by RNase H. The endoribonuclease RNase H is a member of the nucleotidyl-transferase (NT) superfamily and is known to hydrolyze the phosphodiester bonds of RNA which is hybridized to DNA. Retroviral RNase H is part of the viral reverse transcriptase enzyme that is indispensable for the proliferation of retroviruses, such as HIV. Inhibitors of this enzyme could therefore provide new drugs against diseases like AIDS. In our study we investigated the molecular mechanism of RNA cleavage by human RNase H using a comprehensive high level DFT/B3LYP QM/MM theoretical method for the calculation of the stationary points and nudged elastic band (NEB) and free energy calculations to identify the transition state structures, the rate limiting step and the reaction barrier. Our calculations reveal that the catalytic mechanism proceeds in two steps and that the nature of the nucleophile is a water molecule. In the first step, the water attack on the scissile phosphorous is followed by a proton transfer from the water to the O2P oxygen and a trigonal bipyramidal pentacoordinated phosphorane is formed. Subsequently, in the second step the proton is shuttled to the O30 oxygen to generate the product state. During the reaction mechanism two Mg2+ ions support the formation of a stable associated in-line SN2-type phosphorane intermediate. Our calculated energy barrier of 19.3 kcal mol*1 is in excellent agreement with experimental findings (20.5 kcal mol*1). These results may contribute to the clarification and understanding of the RNase H reaction mechanism and of further enzymes from the RNase family.
2010. "Nucleotide Docking: Prediction of Reactant State Complexes for Ribonuclease Enzymes." Journal of Molecular Modeling 17(8):1953-1962. doi:10.1007/s00894-010-0900-8 Abstract Ribonuclease enzymes (RNases) play key roles in the maturation and metabolism of all RNA molecules. Computational simulations of the processes involved can help to elucidate the underlying enzymatic mechanism and is often employed in a synergistic approach together with biochemical experiments. Theoretical calculations require atomistic details regarding the starting geometries of the molecules involved, which, in the absence of crystallographic data, can only be achieved from computational docking studies. Fortunately, docking algorithms have improved tremendously in recent years, so that reliable structures of enzyme–ligand complexes can now be successfully obtained from computation. However, most docking programs are not particularly optimized for nucleotide docking. In order to assist our studies on the cleavage of RNA by the two most important ribonuclease enzymes, RNase A and RNase H, we evaluated four docking tools—MOE2009, Glide 5.5, QXP-Flo+0802, and Autodock 4.0—for their ability to simulate complexes between these enzymes and RNA oligomers. To validate our results, we analyzed the docking results with respect to the known key interactions between the protein and the nucleotide. In addition, we compared the predicted complexes with X-ray structures of the mutated enzyme as well as with structures obtained from previous calculations. In this manner, we were able to prepare the desired reaction state complex so that it could be used as the starting structure for further DFT/B3LYP QM/MM reaction mechanism studies.
2010. "Scale dependence of intragranular porosity, tortuosity, and tortuosity." Water Resources Research 46:Art. No. W06513. doi:10.1029/2009WR008183 Abstract Diffusive exchange of solutes between intragranular pores and flowing water is a recognized but poorly understood contributor to dispersion. Intragranular porosity may also contribute to the slow sorption phenomenon. Intragranular pores may be sparsely interconnected, raising the possibility that accessible porosity and diffusive exchange are limited by pore connectivity. We used a pore-scale network model to examine pore connectivity effects on accessible porosity, diffusivity, and tortuosity in spherical particles. The diffusive process simulated was release of a non-sorbing solute initially at equilibrium with the surrounding solution. High-connectivity results were essentially identical to Crank’s analytical solution. Low-connectivity results were consistent with observations reported in the literature, with solute released more quickly at early times than indicated by the analytical solution, and more slowly at late times. Values of accessible porosity, diffusivity, and tortuosity scaled with connection probability, distance to the sphere’s exterior, and/or the sphere’s radius, as predicted by percolation theory. The scaling relationships should be useful in conventional modeling of diffusive processes in porous spherical particles.
2010. "A New Aerosol Flow System for Photochemical and Thermal Studies of Tropospheric Aerosols." Aerosol Science and Technology 44(5):329-338. doi:10.1080/02786821003639700 Abstract For studying the formation and photochemical/thermal reactions of aerosols relevant to the troposphere, a unique, high-volume, slow-flow, stainless steel aerosol flow system equipped with 5 UV lamps has been constructed and characterized experimentally. The total flow system length 6 is 8.5 m and includes a 1.2 m section used for mixing, a 6.1 m reaction section and a 1.2 m 7 transition cone at the end. The 45.7 cm diameter results in a smaller surface to volume ratio than is found in many other flow systems and thus reduces the potential contribution from wall reactions. The latter are also reduced by frequent cleaning of the flow tube walls which is made feasible by the ease of disassembly. The flow tube is equipped with ultraviolet lamps for photolysis. This flow system allows continuous sampling under stable conditions, thus increasing the amount of sample available for analysis and permitting a wide variety of analytical techniques to be applied simultaneously. The residence time is of the order of an hour, and sampling ports located along the length of the flow tube allow for time-resolved measurements of aerosol and gas-phase products. The system was characterized using both an inert gas (CO2) and particles (atomized NaNO3). Instruments interfaced directly to this flow system include a NOx analyzer, an ozone analyzer, relative humidity and temperature probes, a scanning mobility particle sizer spectrometer, an aerodynamic particle sizer spectrometer, a gas chromatograph-mass spectrometer, an integrating nephelometer, and a Fourier transform infrared spectrophotometer equipped with a long path (64 m) cell. Particles collected with impactors and filters at the various sampling ports can be analyzed subsequently by a variety of techniques. Formation of secondary organic aerosol from α-pinene reactions (NOx photooxidation and ozonolysis) are used to demonstrate the capabilities of this new system.