Water in Biology | DNA Electron Transport Dynamics | Macromolecular Recognition Macromolecular Recognition* Understanding the process of O2 binding to hemoglobin and myoglobin is of importance in biology since these molecules are responsible for the oxygen transportation and storage in mammalian cells. Molecular recognition by biological macromolecules involves many elementary steps, usually convoluted by diffusion processes. However, details are difficult to determine due to the complex nature of the protein structure. Synthetic model porphyrins are used to mimic the structure and function of the proteins so to obtain insights of the correlation between structure and function. Studies of the dynamics, from the femtosecond to the microsecond time scale, of the different elementary processes involved in the bimolecular recognition of a protein mimic, cobalt picket-fence porphyrin, were carried out by transient absorption with varying oxygen concentration at controlled temperatures. Electron transfer, bond breakage, with initial O2 release occuring in 1.9 ps, and thermal “on” (recombination) and “off” (dissociation) reactions are the different processes involved. Consistency for the reported thermodynamics, kinetics and dynamics was achieved by a two-step recognition model, with reversibility being part of both steps. The transient intermediates are configurations defined by the contact between oxygen (diatomic) and the picket-fence porphyrin (macromolecule), without formation of a strong ligand-metal bond. This intermediate is critical in the description of the potential energy landscape, and both enthalpic and entropic contributions to the free energy are important. Most of the diffusion-controlled encounters which lead to the formation of the intermediate do not result in a final bound state, resulting in an effective recombination rate which is much slower than the theoretical (Smoluchowski) diffusion controlled rate. The formation of intermediate structure(s) actually facilitates the final recognition on the global energy landscape which must involve both the diffusion in the solvent and the intramolecular rearrangement of the porphyrin structure. This two-step mechanism is relevant to macromolecular biological processes of enzymes and DNA/drug recognition. It is remarkable that the process in the initial femtosecond/picosecond O2 liberation is similar to that observed for the CO/myoglobin system. *The text above has been adapted from the following publications. Selected Publications RNA-Protein Recognition: Single-Residue Ultrafast Dynamical Control of Structural Specificity and Function, T. Xia, C. Wan, R. W. Roberts, A. H. Zewail, Proc. Natl. Acad. Sci. USA 2005, 102, 13013. The RNA-Protein Complex: Direct Probing of the Interfacial Recognition Dynamics and Its Correlation with Biological Functions, T. Xia, H.-C. Becker, C. Wan, A. Frankel, R. W. Roberts, A. H. Zewail, Proc. Natl. Acad. Sci. USA 2003, 100, 8119. Molecular Recognition of Oxygen by Protein Mimics: Dynamics on the Femtosecond to Microsecond Time Scale, S. Z. Zou, J. S. Baskin, A. H. Zewail, Proc. Natl. Acad. Sci. USA 2002, 99, 9625. Femtosecond Dynamics of Dioxygen-Picket-Fence Cobalt Porphyrins: Ultrafast Release of O2 and the Nature of Dative Bonding, B. Steiger, J. S. Baskin, F. C. Anson, A. H. Zewail, Angew. Chem., Int. Ed. 2000, 39, 257.