Xiangqian Hu

Concerted O atom–proton transfer in the O—O bond forming step in water oxidation

As the terminal step in photosystem II, and a potential half-reaction for artificial photosynthesis, water oxidation (2H2O → O2 + 4e- + 4H+) is key, but it imposes a significant mechanistic challenge with requirements for both 4e-/4H+ loss and O—O bond formation. Significant progress in water oxidation catalysis has been achieved recently by use of single-site Ru metal complex catalysts such as [Ru(Mebimpy)(bpy)(OH2)]2+ [Mebimpy = 2,6-bis(1-methylbenzimidazol-2-yl)pyridine; bpy = 2,2′-bipyridine]. When oxidized from to RuV = O3+, these complexes undergo O—O bond formation by O-atom attack on a H2O molecule, which is often the rate-limiting step. Microscopic details of O—O bond formation have been explored by quantum mechanical/molecular mechanical (QM/MM) simulations the results of which provide detailed insight into mechanism and a strategy for enhancing catalytic rates. It utilizes added bases as proton acceptors and concerted atom–proton transfer (APT) with O-atom transfer to the O atom of a water molecule in concert with proton transfer to the base (B). Base catalyzed APT reactivity in water oxidation is observed both in solution and on the surfaces of oxide electrodes derivatized by attached phosphonated metal complex catalysts. These results have important implications for catalytic, electrocatalytic, and photoelectrocatalytic water oxidation.

Singlet-Triplet Energy Gaps for Diradicals from Fractional-Spin Density-Functional Theory

Open-shell singlet diradicals are difficult to model accurately within conventional Kohn-Sham (KS) density-functional theory (DFT). These methods are hampered by spin contamination because the KS determinant wave function is neither a pure spin state nor an eigenfunction of the S(2) operator. Here we present a theoretical foray for using single-reference closed-shell ground states to describe diradicals by fractional-spin DFT (FS-DFT). This approach allows direct, self-consistent calculation of electronic properties using the electron density corresponding to the proper spin eigenfunction. The resulting FS-DFT approach is benchmarked against diradical singlet-triplet gaps for atoms and small molecules. We have also applied FS-DFT to the singlet-triplet gaps of hydrocarbon polyacenes.

Ab initio quantum mechanical/molecular mechanical simulation of electron transfer process: fractional electron approach.

Electron transfer (ET) reactions are one of the most important processes in chemistry and biology. Because of the quantum nature of the processes and the complicated roles of the solvent, theoretical study of ET processes is challenging. To simulate ET processes at the electronic level, we have developed an efficient density functional theory (DFT) quantum mechanical (QM)/molecular mechanical (MM) approach that uses the fractional number of electrons as the order parameter to calculate the redox free energy of ET reactions in solution. We applied this method to study the ET reactions of the aqueous metal complexes Fe(H(2)O)(6)(2+/3+) and Ru(H(2)O)(6)(2+/3+). The calculated oxidation potentials, 5.82 eV for Fe(II/III) and 5.14 eV for Ru(II/III), agree well with the experimental data, 5.50 and 4.96 eV, for iron and ruthenium, respectively. Furthermore, we have constructed the diabatic free energy surfaces from histogram analysis based on the molecular dynamics trajectories. The resulting reorganization energy and the diabatic activation energy also show good agreement with experimental data. Our calculations show that using the fractional number of electrons (FNE) as the order parameter in the thermodynamic integration process leads to efficient sampling and validate the ab initio QM/MM approach in the calculation of redox free energies.

Theoretical study of catalytic mechanism for single-site water oxidation process

Water oxidation is a linchpin in solar fuels formation, and catalysis by single-site ruthenium complexes has generated significant interest in this area. Combining several theoretical tools, we have studied the entire catalytic cycle of water oxidation for a single-site catalyst starting with [RuII(tpy)(bpm)(OH2)]2+ (i.e., [RuII-OH2]2+; tpy is 2,2′∶6′,2′′-terpyridine and bpm is 2,2′-bypyrimidine) as a representative example of a new class of single-site catalysts. The redox potentials and pKa calculations for the first two proton-coupled electron transfers (PCETs) from [RuII-OH2]2+ to [RuIV = O]2+ and the following electron-transfer process to [RuV = O]3+ suggest that these processes can proceed readily in acidic or weakly basic conditions. The subsequent water splitting process involves two water molecules, [RuV = O]3+ to generate [RuIII-OOH]2+, and H3O+ with a low activation barrier (∼10 kcal/mol). After the key O---O bond forming step in the single-site Ru catalysis, another PECT process oxidizes [RuIII-OOH]2+ to [RuIV-OO]2+ when the pH is lower than 3.7. Two possible forms of [RuIV-OO]2+, open and closed, can exist and interconvert with a low activation barrier (< 7 kcal/mol) due to strong spin-orbital coupling effects. In Pathway 1 at pH = 1.0, oxygen release is rate-limiting with an activation barrier ∼12 kcal/mol while the electron-transfer step from [RuIV-OO]2+ to [RuV - OO]3+ becomes rate-determining at pH = 0 (Pathway 2) with Ce(IV) as oxidant. The results of these theoretical studies with atomistic details have revealed subtle details of reaction mechanisms at several stages during the catalytic cycle. This understanding is helpful in the design of new catalysts for water oxidation.

Exploring biological electron transfer pathway dynamics with the Pathways plugin for VMD.

We describe the new Pathways plugin for the molecular visualization program visual molecular dynamics. The plugin identifies and visualizes tunneling pathways and pathway families in biomolecules, and calculates relative electronic couplings. The plugin includes unique features to estimate the importance of individual atoms for mediating the coupling, to analyze the coupling sensitivity to thermal motion, and to visualize pathway fluctuations. The Pathways plugin is open source software distributed under the terms of the GNUs Not Unix (GNU) public license.

A gradient-directed Monte Carlo approach to molecular design

The recently developed linear combination of atomic potentials (LCAP) approach [M. Wang et al., J. Am. Chem. Soc. 128, 3228 (2006)] allows continuous optimization in a discrete chemical space, and thus is useful in the design of molecules for targeted properties. To address further challenges arising from the rugged, continuous property surfaces in the LCAP approach, we develop a gradient-directed Monte Carlo (GDMC) strategy as an augmentation to the original LCAP optimization method. The GDMC method retains the power of exploring molecular space by utilizing local gradient information computed from the LCAP approach to jump between discrete molecular structures. It also allows random MC moves to overcome barriers between local optima on property surfaces. The combined GDMC-LCAP approach is demonstrated here for optimizing nonlinear optical properties in a class of donor-acceptor substituted benzene and porphyrin frameworks. Specifically, one molecule with four nitrogen atoms in the porphyrin ring was found to have a larger first hyperpolarizability than structures with the conventional porphyrin motif.

Autocatalytic Intramolecular Isopeptide Bond Formation in Gram-Positive Bacterial Pili: A QM/MM Simulation

Many gram-positive pathogens possess external pili or fimbriae with which they adhere to host cells during the infection process. Unusual dual intramolecular isopeptide bonds between Asn and Lys side chains within the N-terminal and C-terminal domains of the pilus subunits have been observed initially in the Streptococcus pyogenes pilin subunit Spy0128 and subsequently in GBS52 from Streptococcus agalactiae, in the BcpA major pilin of Bacillus cereus and in the RrgB pilin of Streptococcus pneumoniae, among others. Within each pilin subunit, intramolecular isopeptide bonds serve to stabilize the protein. These bonds provide a means to withstand large external mechanical forces, as well as possibly assisting in supporting a conformation favored for pilin subunit polymerization via sortase transpeptidases. Genome-wide analyses of pili-containing gram-positive bacteria are known or suspected to contain isopeptide bonds in pilin subunits. For the autocatalytic formation of isopeptide cross-links, a conservation of three amino acids including Asn, Lys, and a catalytically important acidic Glu (or Asp) residue are responsible. However, the chemical mechanism of how isopeptide bonds form within pilin remains poorly understood. Although it is possible that several mechanistic paths could lead to isopeptide bond formation in pili, the requirement of a conserved glutamate and highly organized positioning of residues within the hydrophobic environment of the active site were found in numerous pilin crystal structures such as Spy0128 and RrgB. This suggests a mechanism involving direct coupling of lysine side chain amine to the asparagine carboxamide mediated by critical acid/base or hydrogen bonding interactions with the catalytic glutamate residue. From this mechanistic perspective, we used the QM/MM minimum free-energy path method to examine the reaction details of forming the isopeptide bonds with Spy0128 as a model pilin, specifically focusing on the role of the glutamate in catalysis. It was determined that the reaction mechanism likely consists of two major steps: the nucleophilic attack on Cγ by nitrogen in the unprotonated Lys ε-amino group and, then two concerted proton transfers occur during the formation of the intramolecular isopeptide bond to subsequently release ammonia. More importantly, within the dual active sites of Spy0128, Glu(117), and Glu(258) residues function as crucial catalysts for each isopeptide bond formation, respectively, by relaying two proton transfers. This work also suggests that domain-domain interactions within Spy0128 may modulate the reactivity of residues within each active site. Our results may hopefully shed light on the molecular mechanisms of pilin biogenesis in gram-positive bacteria.

Analysis of HIF-1 inhibition by manassantin A and analogues with modified tetrahydrofuran configurations

We have shown that manassantin A downregulated the HIF-1alpha expression and inhibited the secretion of VEGF. We have also demonstrated that the 2,3-cis-3,4-trans-4,5-cis-configuration of the tetrahydrofuran is critical to the HIF-1 inhibition of manassantin A.

Parallelization of MRCI based on hole-particle symmetry.

The parallel implementation of multireference configuration interaction program based on the hole‐particle symmetry is described. The platform to implement the parallelization is an Intel‐Architectural cluster consisting of 12 nodes, each of which is equipped with two 2.4‐G XEON processors, 3‐GB memory, and 36‐GB disk, and are connected by a Gigabit Ethernet Switch. The dependence of speedup on molecular symmetries and task granularities is discussed. Test calculations show that the scaling with the number of nodes is about 1.9 (for C1 and Cs), 1.65 (for C2v), and 1.55 (for D2h) when the number of nodes is doubled. The largest calculation performed on this cluster involves 5.6 × 108 CSFs.

Variational fractional-spin density-functional theory for diradicals.

Accurate computation of singlet-triplet energy gaps of diradicals remains a challenging problem in density-functional theory (DFT). In this work, we propose a variational extension of our previous work [D. H. Ess, E. R. Johnson, X. Q. Hu, and W. T. Yang, J. Phys. Chem. A 115, 76 (2011)], which applied fractional-spin density-functional theory (FS-DFT) to diradicals. The original FS-DFT approach assumed equal spin-orbital occupancies of 0.5 α-spin and 0.5 β-spin for the two degenerate, or nearly degenerate, frontier orbitals. In contrast, the variational approach (VFS-DFT) optimizes the total energy of a singlet diradical with respect to the frontier-orbital occupation numbers, based on a full configuration-interaction picture. It is found that the optimal occupation numbers are exactly 0.5 α-spin and 0.5 β-spin for diradicals such as O(2), where the frontier orbitals belong to the same multidimensional irreducible representation, and VFS-DFT reduces to FS-DFT for these cases. However, for diradicals where the frontier orbitals do not belong to the same irreducible representation, the optimal occupation numbers can vary between 0 and 1. Furthermore, analysis of CH(2) by VFS-DFT and FS-DFT captures the (1)A(1) and (1)B(1) states, respectively. Finally, because of the static correlation error in commonly used density functional approximations, both VFS-DFT and FS-DFT calculations significantly overestimate the singlet-triplet energy gaps for disjoint diradicals, such as cyclobutadiene, in which the frontier orbitals are confined to separate atomic centers.