|Research in the Stephens group spans the fields of Theoretical Chemistry, Molecular Spectroscopy, Optical Activity and Bioinorganic Chemistry. The current focus is principally in two areas:|
1) Natural Optical Activity
Chiral molecules exhibit optical activity. We are currently developing new theoretical techniques for the prediction of the Vibrational Circular Dichroism, Electronic Optical Rotation and Electronic Circular Dichroism of chiral molecules. The common ingredient in these developments is the use of ab initio Density Functional Theory (DFT). The new theoretical techniques provide new methodologies for elucidating the stereochemistry of chiral molecules - in particular, their absolute configuration and conformation. Studies of medium sized organic molecules have demonstrated the practicality of these methodologies. Applications are ongoing in the fields of 1) natural product structure; 2) chiral drug characterization; 3) chiral polymers; 4) chiral catalysis; 5) peptide and protein structural analysis.
The Vibrational Circular Dichroism of Trögers' Base demonstrates that its Absolute Configuration is (R,R) - (-).
2) Bioinorganic Chemistry
Many metalloproteins are redox active. Proteins which are involved in electron transport cycle between oxidized and reduced states. Their redox potentials determine their physiological functions. Understanding the way in which proteins control the redox potentials of metal-containing prosthetic groups is fundamental to understanding the physiological function of electron transport metalloproteins. We are currently developing and applying new theoretical techniques for predicting the redox potentials of metalloproteins. Studies carried out to date have focused on iron-sulfur proteins. Initial studies using a classical electrostatic model have been very encouraging. Future studies will extend this work 1) by using more sophisticated theoretical models, incorporating quantum mechanical techniques; 2) to a wider selection of proteins, including heme, non-heme iron and copper proteins.
of Vibrational Circular Dichroism, P.J. Stephens, J. Phys. Chem., 89,
Initio Calculation of Atomic Axial Tensors and Vibrational Rotational Strengths
Using Density Functional Theory, J.R. Cheeseman, M.J. Frisch, F.J. Devlin
and P.J. Stephens, Chem. Phys. Lett., 252, 211 (1996).
Initio Prediction of Vibrational Absorption and Circular Dichroism Spectra
of Chiral Natural Products Using Density Functional Theory: Camphor and
Fenchone, F.J. Devlin, P.J. Stephens, J.R. Cheeseman and M.J. Frisch, J.
Phys. Chem., 101, 6322 (1997).
Structure in Solution: An Ab Initio Vibrational Spectroscopy Study of
Phenyloxirane, C.S. Ashvar, F.J. Devlin, and P.J. Stephens, J. Am. Chem. Soc., 121,
||Conformational Analysis Using
Ab Intiio Vibrational Spectroscopy: 3-Methylcyclohexanone,
F.J. Devlin and P.J. Stephens, J. Am. Chem. Soc., 121, 7413-7414 (1999).
Absorption and Circular Dichroism Spectra and Absolute Configuration of
Troger’s Base, A. Aamouche, F.J. Devlin and P.J. Stephens, J. Am.
Chem. Soc., 122, 2346-2354 (2000).
||Determination of the
Structure of Chiral Molecules Using Ab Initio Vibrational Circular
Dichroism Spectroscopy, P.J. Stephens and F.J. Devlin, Chirality, 12,
||Determination of Absolute
Configuration Using Vibrational Circular Dichroism Spectroscopy:
1-(2-Methyl-Naphthyl) Methyl Sulfoxide, P.J. Stephens, A. Aamouche,
F.J. Devlin, S. Superchi, M.I. Donnoli and C. Rosini, J. Org. Chem., 6,
||The Calculation of Optical
Rotation Using Density Functional Theory, P.J. Stephens, F.J. Devlin, J.R.
Cheeseman and M.J. Frisch, J. Phys. Chem. A, 105, 5356-5371 (2001).
||Protein Control of
Iron-Sulfur Cluster Redox Potentials, R. Langen, G.M. Jensen, U. Jacob,
P.J. Stephens and A. Warshel, J. Biol. Chem., 267, 25625 (1992).
||Calculation of the Redox
Potentials of Iron-Sulfur Proteins: The 2-/3- Couple of [Fe4S4Cys4]
Clusters in Peptococcus Aerogenes Ferredoxin, Azotobacter vinelandii
Ferredoxin I and Chromatium vineosum HiPIP, G.M. Jensen, A. Warshel and
P.J. Stephens, Biochemistry, 33, 10911 (1994).
||The Protein Control of the
Redox Potentials of Iron-Sulfur Proteins, P.J. Stephens, D.R. Jollie and
A. Warshel, Chem. Rev. (Bioinorganic Enzymology), 96, 2491 (1996).