Current Inorganic Chemistry (v.2, #3)

Force fields were intended to be the more general possible. However, the and#x201C;missing parameterand#x201D; problem is a major drawback on the application of classical molecular dynamics simulations to study metalloenzymes. Biomolecular force field parameter sets were initially designed only for organic molecules. The treatment of transition metals is not as straightforward. Metals can have several different types of ligands and the metal-coordination sphere is often flexible with several different geometries possible. The electronic effects of the partially filled d-orbitals make the application of molecular mechanics methods more complicated. Careful consideration of the metal correct charge and spin state should also be taken into account before parameterization. Consequently, the parameters for bioinorganic systems are usually scarce and prior metal coordination spheres parameterization is required. In this review is given a very brief discussion about how the parameters for two widely used force fields, AMBER and CHARMM, were derived. This is followed by a discussion on the feasibility of adding new force field parameters for bioinorganic systems and the possible approaches to attain that objective. Examples are given at the end.

Using QM/MM Methods for the Exploration of Electron Transfer Pathways by Maria F. Lucas, Diego Masone, Suwipa Saen-oon, Frank Wallrapp, Victor Guallar (263-272).
Many proteins are known for their ability to perform several functions such as oxidation/reduction, gas transport or storage and electron transfer depending on the active site's environment or on the available ligands. Consequently, the interest in an atomic (and electronic) description of these functionsand#x2019; mechanism is very high. However, obtaining such detailed information is not a trivial task. The continued growth of computer power and the development of theoretical techniques, such as mixed quantum mechanics and molecular mechanics, permit the atomistic study of complex biological systems. Here, recent computational advances in protein electron transfer studies on our group are reviewed. We centered our attention on long distance electron transfer processes and the application of the QM/MM e-pathway method to protein systems.

Heme-binding proteins play a variety of critical roles in biology. The functional versatility of this prosthetic group is attributed to the influence of the polypeptide on the electronic structure and thus reactivity of the heme. NMR spectroscopy is well suited to simultaneously probe molecular structure, dynamics, and electronic structure of heme proteins in paramagnetic states. In this review, an overview of recent advances in the heme protein field enabled by NMR spectroscopy is presented, with a focus on paramagnetic heme proteins. Examples of NMR studies of cytochromes c, globins, nitrophorins, cytochrome P450, hemophores, and heme oxygenases are discussed. Heme protein biochemistry and NMR methodology have seen significant advances in the past decade, and it is expected that NMR will continue to play a central role in our developing understanding of heme protein structure, dynamics, and function.

Quantum-Mechanical Studies of Reactions Performed by Cytochrome P450 Enzymes by Patrik Rydberg, Lars Olsen, Ulf Ryde (292-315).
We review density functional theory studies of various types of reactions performed by the cytochrome P450 family of enzymes. We describe the various reactions on equal footing with an emphasis on models to predict sites of metabolism for an arbitrary molecule. The activation barriers range between 0 and 109 kJ/mol, depending more on the atoms surrounding the reactive site than on the type of reaction. Therefore, the intrinsic reactivity can rather well be predicted by simple chemical rules. However, for a full predictive model, the steric effects of the enzyme surrounding the heme group also need to be modeled, which is often harder.

Recent computational work on the metal centres of the respiratory haem-copper oxidases is reviewed, with a focus on the eukaryotic cytochrome c oxidase. First, state-of-the-art quantum chemical methodologies are discussed, followed by an overview of studies of the ground state electronic structure, the foundation for more elaborate and complex mechanistic and spectroscopic studies on the systems. Special emphasis is placed on spin and charge distributions.

Salen Mn Complexes are Superoxide Dismutase/Catalase Mimetics that Protect the Mitochondria by Susan R. Doctrow, Marc Liesa, Simon Melov, Orian S. Shirihai, Philip Tofilon (325-334).
Salen Mn complexes, including EUK-134, EUK-189 and a cyclized analog EUK-207, are synthetic superoxide dismutase (SOD) and catalase mimetics that are beneficial in many models of oxidative stress. Though not designed to target the mitochondria, salen Mn complexes show and#x201C;mito-protectiveand#x201D; activity, that is, an ability to attenuate mitochondrial injury, in various experimental systems. Treatment with EUK-134 prevents respiratory chain abnormalities induced by ionizing radiation in rat astrocyte cultures. Treatment with salen Mn complexes also prolongs survival, protects mitochondrial enzymes and prevents oxidative pathologies in Sod2-/- mice, which lack the mitochondrial form of superoxide dismutase. Recently, EUK-207 was shown to attenuate ischemia reperfusion injury, including mitochondrial dysfunction, in hearts from ABC-me-/+ mice, which are deficient in a mitochondrial transporter and more vulnerable to oxidative stress. Since mitochondrial dysfunction has been implicated in many forms of injury and degeneration, this and#x201C;mito-protectiveand#x201D; property may explain some of the cytoprotective effects of salen Mn complexes in vivo, and may also enhance their potential therapeutic value.

Acknowledgement by Bentham Science Publishers (335-335).
Bentham Science Publishers would like to thank and appreciate the co-operation from all reviewers for their constructive comments and feedback on the manuscripts submitted to Current Inorganic Chemistry. Their efforts have contributed greatly to the high quality and continuous growth of the journal. Given below is the list of reviewers who reviewed articles for the Journal during 2012: