Professor, Biomedical and Chemical Engineering and Sciences
BSc (Hons) University of St. Andrews, Scotland 1987
PhD University of St. Andrews, Scotland 1991
General Chemistry, Bio-inorganic Chemistry, Green Chemistry
Inorganic Chemistry and Biological Systems
Bioinorganic chemistry is the study of inorganic species in biological systems. We are working in a number of areas of research involving bioinorganic chemistry including: the design of new metal-based artificial endonucleases for use as molecular biology tools, antiviral and antibacterial drugs based on the octahedral cobalt hexammine coordination complex (as shown), phosphonic acid functionalized organometallics based on rhenium and technetium as bone-seeking agents and new paradigms for achieving intracellular organic synthesis using water-stable encapsulated transition metal catalysts. We are also developing a number of catalysts for the asymmetric synthesis of phosphorus containing pharmaceuticals.
Inorganic Chemistry and Energy
We have been developing organometallic phosphonates and phosphonic acids for a number of applications including aqueous phase homogeneous catalysis, metal oxide supported catalysis and the formation of organometallic monolayers. The phosphonic acid group PO3H2 is particularly useful for immobilizing molecules to oxide surfaces. Thus, monolayers of redox-active ruthenium complexes functionalized with -PO3H2 have been adsorbed to nanocrystalline TiO2 and TiO2 modified ITO. Electronic coupling with the surface is achieved allowing efficient light-induced charge separation and such systems show promise in the fabrication of devices for the conversion of light to electricity. The clear advantage of the phosphonic acid group over sulfonic and carboxylic acids is the lack of desorption of the acid from the TiO2 surface over a wide pH range. We have previously demonstrated the formation of phosphine coordinated Pt or Mo complexes containing these ligands and confirmed the structure of the meta-isomer of the free m-TPPTP ligand by X-ray crystallography.
Analogous palladium complexes, prepared in situ, were shown to be effective catalysts for the formation of C-P bonds in both homogeneous solution and as heterogeneous species adsorbed to silica particles. In addition, the ability to form monolayer films of complexes, required for future studies of these species as heterogeneous catalysts and building blocks for the formation of 2D/3D supramolecular structures, was illustrated by the stepwise synthesis and characterization of a molybdenum based mono-TPPTP (TPPTP = triphenylphosphine triphosphonic acid) complex monolayer on an Al2O3).The objective of this project is the synthesis and characterization of organometallic multilayered serial hetero-structures and nanomaterials which may be used as electro-active catalysis.
Inorganic Chemistry and Defense
We are currently exploring the use of metal-based coordination compounds as artificial endonucleases and antiviral agents as counter-measures for biological threat agents such as Ebola and Venezuelan Equine Encephalitis (VEE). A large number of synthetic main group and transition metal complexes are known to act as artificial phosphodiesterases i.e. they can cleave the phosphodiester linkage found in naturally occurring RNA and DNA. These complexes can also be described as chemical nucleases or more specifically chemical endonucleases when the RNA or DNA is cleaved at internal sites in the nucleotide sequence. As such, these molecules can potentially act as biomimetic restriction enzymes. Metal-based artificial phosphodiesterases however, have no specificity, i.e. they will indiscriminately cut nuclear material. If DNA-binding and sequence-recognition properties are built into the system, these chemical nucleases will have antisense properties, so that these systems can also be thought of as having antisense-plus properties. The proposed artificial endonuclease will have the ability to recognize a specific sequence of nucleotides and to hydrolyze the target's phosphodiester bond. Therefore, the system should consist of (a) a metal-centered catalytic moiety attached to (b) a nucleotide sequence recognition region.In collaboration with Dr. Eddie Chang at the Naval Research Laboratory (NRL), we are exploring the possibility that these artificial endonucleases can be used as potent anti-viral therapeutics.
Inorganic Chemistry and Green Synthesis
Green Chemistry is a philosophy which promotes the design of chemical products and processes which eliminate the use and generation of hazardous substances. Green Chemistry can be described using the 12 Principles of Green Chemistry: http://www.epa.gov/greenchemistry/pubs/principles.html
We have a number of projects in the field of green chemistry including: (a) the use of unusual solvent media e.g. ionic liquids for organic transformations (b) development of new water-soluble catalysts for aqueous phase homogeneous catalysis and (c) new reactions involving C1 feedstocks for increased atom efficiency.
Inorganic Chemistry and Organic Synthesis
We are interested in the use of inorganic and organometallic coordination complexes as catalysts for a number of important organic transformations including carbonylation, hydroformylation, phosphonylation, oxidation and asymmetric synthesis.
The catalytic oxidative functionalization of non-methane (C2+) hydrocarbon feedstocks such as ethane, ethylene and propane has been inadequately achieved using homogeneous catalysis despite this being the desired catalytic method of choice for a variety of very important organic transformation such as the hydroformylation amidocarbonylation of alkenes. On the other hand, heterogeneous catalysts are largely used for oxidative functionalization but their potential performance has yet to be realized to any great extent. For some time now, the growth of discreet, single-site partial oxidation (Pox) catalysts has hinted at a potential solution to the problem, but has been thwarted by difficulties in catalyst characterization and synthesis, and the lack of catalyst robustness given the often extreme reaction conditions. Supported molecular catalysts that add other elements such as nitrogen, sulfur and phosphorus to hydrocarbons are also highly desirable but to this date remain undiscovered. We are investigating phosphonic acid functionalized nanoparticles to achieve these organic transformations.
This work is being pursued in collaboration with Professor Bruno Bujoli, University of Nantes, France.
Synthesis of a 2,2'-Bipyridyl Functionalized Oligovinylenephenylene Using Heck and Horner-Wadsworth-Emmons Reactions and X-Ray Crystal Structure of E-(4-(4-bromostyryl)phenyl)(methyl)sulfane Karácsony, O.; Deschamps, J.; Trammell, S. A.; Nita, R.; Knight, D. A. Molecules 2012, 17, 5724-5732.
Electronic Effects on the Reactivity of Copper Mono-Bipyridine Complexes of Formula Cu(4,4'-R2-2,2'-bipyridine)X2, R = NO2, Cl, H, CH3, OCH3, and X = NO3-, Cl- Moore, M.; Knight, D. A.; Zabetakis, D.; Deschamps, J.; Dressick, W.; Chang, E.; Trammell, S. Inorganic Chimica Acta 2011, 388, 168-174.
Accelerating the Initial Rate of Hydrolysis of Methyl Parathion with Laser Excitation using Monolayer Protected 10 nm Au Nanoparticles Capped with a Cu(bpy) Catalyst Trammell, S. A.; Nita, R.; Moore, M.; Chang, E. L.; Knight, D. A. Chem. Commun. 2012, 48, 4121-4123.
Surface Modification Using Phosphonic Acids and Esters Petit, M.; Janvier, P.; Knight, D. A.; Bujoli, B. Chem. Rev, 2012, 112, 3777.
Oxidation of Trimethoprim by Ferrate(VI): Kinetics, Products, and Antibacterial Activity Anquandah, G. A. A.; Sharma, V. K.; Knight, D. A.; Batchu, S. R.; Gardinali, P. R. Environ. Sci. Tech. 2011, 45, 10575–10581.
Hexamminecobalt(III) Chloride as a Broad-Spectrum Antiviral Complex Chang, E. L.; Olinger, G. G.; Hensley, L. E.; Lear, C. M.; Scully, C. E.; Mankowsi, M. K.; Ptak, R. G.; Thach, D. C.; Knight, D. A.; J. Antivirals and Antiretrovirals 2011, 3, 20-27.
Poly[aqua(μ-vinylphosphonato)cadmium] Congiardo, L. K. B.; Mague, J. T.; Funk, A.; Yngard, R.; Knight, D. A. Acta. Crys. E. 2011, E67, m450-m451.