Exploring possible candidate molecules for cleaving multiple bonds

Free Radical Chemistry: Free radicals are ubiquitous in chemistry, biology, and polymer science. Because they are reactive species, they are often difficult to study experimentally and therefore theory has a potentially useful role to play in their characterisation. Researchers at the University of Sydney and the Australian National University are using state-of-the-art ab initio quantum chemistry calculations to determine radical stabilisation energies, with the important aim of seeing how individual substituents stabilise or destabilise a radical centre. Details of radical addition reactions and radical abstraction reactions, both of which are very important in biological chemistry and polymer chemistry, are also being examined.

Polymer Chemistry: Free-radical polymerisation is an important industrial process, used to produce a wide range of polymers. Methods for controlling free-radical polymerisation, such as the Australian-invented RAFT procedure, are a major new development in this field as they allow for production of polymers with narrow molecular weight distributions, well-defined end-groups and special architectures, such as blocks and stars. However, such procedures are difficult to optimise and have not as yet been successfully applied to several important monomers. Researchers at the Australian National University are currently using quantum chemistry to study the mechanism and kinetics of these processes, with a view to providing guidelines for optimising them, and extending their application to new systems. Quantum chemistry is also being used to improve models for copolymerisation kinetics, and to develop strategies for achieving end-group control in conventional radical polymerisation.

Oxides and Hydroxides of Alkali and Alkaline Earth Metals: Researchers at the University of Sydney, in collaboration with the Weizmann Institute of Science in Israel, and the Argonne National Laboratory and the University of North Texas in the USA, the alkali metal oxides and hydroxides are being examined as a preliminary to investigating their interesting acid and base properties. Reliable experimental data are very sparse for these molecules and so it is attractive to obtain the information theoretically. It turns out, however, that the theoretical description of these molecules is not entirely straightforward either and this is necessitating incorporation of several new features in the theoretical procedures that are being used, and the development of new basis sets.

Development of Improved Theoretical Procedures: The ability to predict reliable thermochemistry represents a very important application of ab initio molecular orbital theory. Researchers at the University of Sydney, are designing and assessing methods that are suitable for predicting accurate thermochemistry for free radicals because these represent particular challenges for theoretical investigation. Some of the recently developed methods include G3-RAD, G3X-RAD, G3(MP2)-RAD and G3X(MP2)-RAD. Further work, in collaboration with quantum chemists in the USA, is aimed at handling systems that are not well described by a single-reference wave function.

Small Molecule Activation in Transition Metal Complexes: Manipulation of fundamental small molecules such as N₂, O₂ and CO₂ is crucial, in both a biological and an industrial sense, for our continued wellbeing. Finding new ways of achieving such activation is important due to the enormous costs of current industrial processes which involve activating or cleaving the multiple bonds in these molecules. In light of this, dinuclear metal systems based on sterically-hindered, three-coordinate transition metal complexes of the type (R_nX)₃M where the R_nX are ancillary ligands and R is a bulky organic substituent, hold great promise synthetically for the activation and scission of small, multiply-bonded molecules, L₍₁₎ ≡ L₍₂₎ and L₍₁₎ ≡ L₍₂₎-L₍₃₎, such as N₂, NO, CO and N₂O. Researchers at the ANU and University of Tasmania have employed DFT and hybrid QM/MM methods to design three-coordinate transition metal complexes that are specific for the activation of N₂ and other key small molecules. The calculations show that the level of activation can be controlled through systematic variation of both the metal and its substituents. Through judicious tuning of M, M', X and X', it is not only possible to identify those metal/ligand combinations which achieve optimum activation of each small molecule of interest, but also selective cleavage of bonds in non-symmetric molecules such as N₂O.

Structure and Dynamics of Small Metal Clusters: The group at Newcastle University have developed both theory and code in order to understand the dynamics of small metal clusters, thereby assisting in their possible detection.　

The Potassium Ion Channel

      
Oxidative Damage to Proteins: An understanding of the oxidation of proteins by free radicals is of great importance because of its implication in a number of human disorders such as Alzheimer.s disease, atherosclerosis, and diabetes, as well as aging. A collaborative venture between researchers at the University of Sydney, the Australian National University, the Heart Research Institute, Sydney and the University of Calgary, Canada is using ab initio molecular orbital calculations to address the problem. Initial targets have included the cleavage of the peptide backbone following radical formation, and migration of the radical site within the peptide.

Enzyme-Catalysed Reactions: Vitamin B12 is one of nature's essential vitamins. Quantum chemists at the University of Sydney, are using ab initio calculations to model reactions mediated by coenzyme B12. Although these reactions have been extensively studied experimentally, there is certainly no consensus as to how they proceed. The Sydney group has found that protonation and/or deprotonation at appropriate sites facilitates the reactions, and that reactions that are facilitated by protonation (or deprotonation) are facilitated by the partial-proton-transfer that enzymatic hydrogen bonding can provide. Supporting evidence for these proposals has come from site-directed mutagenesis experiments. This and other recent examples provides strong encouragement for the use of computer calculations in a predictive manner in the study of enzyme-catalysed reactions.

Interaction of Metal Ions With Biological Systems: Metal ions are of great importance in biological function. In work at the University of Sydney, a theoretical study has been initiated to probe the interaction of metal ions with prototypical biological molecules. The initial studies, in collaboration with a quantum chemistry group in Madrid, Spain, have focused on the interaction of calcium dications with simple model systems in order to establish suitable theoretical procedures that can be applied to larger molecules.

Computer aided drug design: At the University of Tasmania computational chemistry techniques are being used to model biologically active compounds, and to design new substrates in separation science. Techniques used include ab initio and density functional theories for sophisticated calculations and simpler molecular mechanics models. Current work is focused on organometallic reaction mechanisms (involving imidazole based carbenes and 3-coordinate molybdenum complexes), and the intermolecular interaction of molecules in medicinal and industrial applications.　

Electronic structure computations on solids and surfaces present their own challenges, notably the possible periodic nature of the systems and the possible high degree of electron delocalization. To date the majority of computations have been performed using density functional theory, although there is interest in using wavefunction based methods like Hartree-Fock and coupled-cluster theories. To study surface reactions the Carr-Parinello method, which combined elements of electronic structure theory with molecular dynamics is widely used.

A simple cubic structure as typified by NaCl

Surface Integrated Molecular Orbital Molecular Mechanics (SIMOMM): this new method has recently been developed by network members from the Iowa State University and is used for the description of surface phenomena. Initial applications have been primarily to the Si(100) surface, studying its structure, oxidation and etching, functionalization and other reactions. SiC and diamond surfaces have also been considered. Efforts are being made to expand the capabilities of this method to many other types of surfaces. For metals, embedded cluster methods like SIMOMM are, however, of limited utility, hence work is under way to develop periodic boundary condition capabilities for Hartree-Fock, density functional theory and MCSCF wave functions. When combined with new linear scaling techniques, these methods will enable the study of surface phenomena for a wide range of problems.

Development of quantum electronic-vibrational simulation techniques for the interpretation of biochemical data including electronic spectroscopy, Stark spectroscopy, EPR spectroscopy and electrochemistry, including understanding the results of extensive mutation studies

Coupled Cluster Methods and Density Functional Theory (DFT): Coupled Cluster Methods, such as SAC-CI or EOM-CC are currently the most accurate, but most expensive method for studying excited electronic states. DFT is a popular alternative approach to excited states that is much more accurate than simple SCF theory, but considerable less expensive than coupled-cluster theories. Work at the ANU is currently considering both coupled-cluster and DFT methods for excited states, with particular interest in ways of improving the long range behaviour of DFT functionals, as this is important for describing Rydberg states. Excited state gradients for DFT have been developed but are not, as yet, widely available.

Multi-Reference Method Development: Multi-reference methods are ideally suited for dealing with excited electronic states, especially multireference configuration interaction (MRCI) and multireference perturbation theory (MRPT), as well as the simpler single excitation CI. The introduction of energy derivatives for all of these methods greatly facilitates the study of excited state potential energy surfaces, that is, photochemistry, photophysics and photobiology. At Iowa State University the GAMESS quantum chemistry package has recently been augmented to include the RESC method and Douglas-Kroll through third order (gradients through first order), as well as the more traditional Breit-Pauli approach, we can now handle spin-orbit coupling and other relativistic effects at many levels of theory. Future work plans to develop and implement derivative (i.e., vibronic) coupling capability in order to better handle such phenomena as conical intersections. A new version of GAMES is also about to be released including equations of motion coupled cluster theory including triples, that is, EOM-CCSD(T).　

Depending on the system distant intermolecular interactions can frequently be treated using some type of empirical interaction potential. Development of such potentials often requires the use of high quality electronic structure calculations. Thus models for solvations are often based on using a few explicit water molecules close to the solute coupled with a more appoximate treatment of more distant waters. In some cases distant water molecules are treated implicitly by placing the solute in a fictitious charged cavity.

Cluster of 21 water molecules

　

Simple models for hydrogen bond energies: Researchers at the University of New England are pioneering techniques for making quantitative predictions of hydrogen bond energies, demonstrating the application of their techniques to the extraction of intermolecular interaction energies from X-ray diffraction data. Only in the last few years have experimental methods enabled the application of these quantitative methods of analysis. Recent work has provided a firm foundation for the extraction of molecular moments and intermolecular interaction energies from diffraction data.

Exploring Non-Covalent Solute-Solvent Interactions in the Gas Phase: Non-covalent interactions between polypeptides and proteins play a major role in determining the chemical and physical behavior of biomolecular polymers. Indeed, a delicate balance between intramolecular interactions and solvation has a significant impact on whether or not many biomolecules exhibit biological and ultimately physiological activity. Researchers at the University of Adelaide are studying small micro-solvated molecules of biological relevance in an attempt to determine how non-covalent hydrogen bonding interactions determine molecular and electronic structure. This work involves a combination of theoretical calculation and gas phase

Transition metal complexes exhibit an enormous variety of structures including classic inorganic coordination compounds, multiply-bonded polynuclear transition metal clusters, organometallic complexes and the metal sites in metalloproteins. The calculation of the electronic structure and properties of these systems however, remains a challenging area of study due to the open-shell nature of many of these systems. Even with the enormous developments in computer hardware, electronic structure calculations on open-shell metal systems using ab initio molecular-orbital methods are still a formidable task due to the high level of electron correlation present, and really only feasible on the simplest systems. In recent years however, density functional theory (DFT) has emerged as an attractive alternative for electronic structure calculations on metal-based systems. Because of the computational expediency of DFT methods, even large systems can be easily handled. Furthermore, the inclusion of electron correlation implicit within DFT ensures that the calculated properties are often in better agreement with experiment than even post-Hartree-Fock ab initio methods. More recently, the development of hybrid QM/MM methods has allowed calculations on very large systems containing many hundreds of atoms, making it now possible to perform calculations on biomolecules containing metal ions.

Metal-Metal Interactions: Metal-metal interactions are very common in dinuclear and polynuclear metal complexes and play an important role in determining their magnetic, electronic and catalytic properties. Researchers at the ANU are studying metal-metal bonding in dinuclear and polynuclear transition metal complexes with the overall aim to identify and quantify the underlying electronic factors that affect the extent and type of metal-metal interaction. Density functional methods combined with the broken-symmetry approach to analyzing the magnetic interactions between metal centers, has proven to be a reliable and efficient procedure for calculating the geometries and magnetic properties of dinuclear complexes spanning the whole range of metal-metal interactions from weak magnetic coupling through to multiple metal-metal bonding. Using this approach, they have determined the periodic and redox-induced trends in metal-metal bonding for a whole series of dⁿdⁿ (n = 1-5) dinuclear complexes as well as dⁿd^n-1 (n = 2-5) mixed-valence systems. These calculations have established the strong dependence of the metal-metal bonding on key electronic factors such as the unpaired spin-density on the metal centers.

Nitrogen Activation via 3-Coordinate Molybdenum Complexes: Using the ONIOM hybrid approach researchers at the University of Tasmania are studying the activation of nitrogen (N2) using three-coordinate molybdenum complexes. The aim of this project is to find facile pathways for the conversion of atmospheric nitrogen to synthetically useful products.

Heavy metal systems: To describe correctly the electronic structure of heavy metals is particularly challenging. Researchers at the University of Melbourne are working on the development of relativistic models. Of particular interest is the modelling of radiative processes in X-ray spectroscopy, providing tests for models incorporating quantum electrodynamics.　

Developing scalable methods has been strongly driven by technology. In the first instance developing a method for which the cost increases linearly with system size requires careful use of distant dependent cutoffs; this is only possible once the molecule has dimensions larger than the relevant cutoff radius. Roughly speaking this requires molecules with a hundred plus atoms, and developing non-scalable electronic structure methods to tackle systems of this size is a challenge in its own right. In the second instance developing methods where the cost decreases linearly with number of processors (computers) required the development of parallel computers. Such hardware really only emerged in the late 80's and was not widespread until the mid to late 90's. Today, although it is possible for a university research group to build their own parallel computing environment using off the shelf technology (so called Beowulf clusters), developing codes that can utilize this environment efficiently remains a considerable challenge. 　

The Pentium IV Cluster at the APAC National Facility

The ANU Supercomputer Facility: For several years the computational chemistry group at the ANU Supercomputer Facility have been working with Fujitsu to produce highly efficient parallel versions of a number of computational chemistry codes. Recent work has focused on the widely used Gaussian quantum chemistry code and the Amber molecular dynamics code. The group are working in collaboration with researchers in the John Curtin School of Medical research to apply linear scaling and hybrid quantum mechanical/molecular mechanical methods to study enzyme reaction pathways.

Scalable Electronic Structure Methods for Shared Memory Systems: Researchers in the ANU department of computer science are working with Sun Microsystems and Gaussian Inc to further develop and improve the parallel performance of the linear scaling methods within the Gaussian quantum chemistry package. The focus is on shared memory architectures and use of the OpenMP parallel programming paradigm. In addition to measuring performance on existing computer architectures the project also aims to simulation performance on possible future architectures. Using only 8 processors related application work is performing computations on systems containing several thousand atoms.

The GAMESS Code: The group at Iowa State University and its collaborators have undertaken significant work to parallelise the GAMESS electronic structure code. This is especially true for correlated wave functions. The implementation is based around the distributed data interface (DDI) which allows very large arrays of data, such as the electron repulsion integrals, to be distributed among all available nodes on a parallel machine. Highly parallel codes already exist for closed and unrestricted open shell second order perturbation theory energies and gradients. These scale to at least 512 processors. Analogous code for spin-restricted open shell second order perturbation theory gradients is in progress. Parallel multi-reference second order perturbation methods have been implemented and work is underway on a scalable MCSCF and full CI code. As well as producing efficient parallel implementation consideration is also being given to reducing the effort required for highly correlated calculations; this aims to dramatically increase the sizes of problems that can be addressed.