DESIGN AND ENGINEERING OF I) AMINO ACID SCHIFF BASE COMPLEXES AND II) CUPREDOXIN AZURIN AND CUA AZURIN

Abstract

With the burgeoning interest for understanding nature, an interdisciplinary overlay ubstantiates a better achievement. This can be evidenced by the strongly overlaid biomimetic supramolecular chemistry and biochemistry. Studying the crystal engineering of the metal-amino acid Schiff bases is the first focus of the study. We chose to investigate the architecturally rich arginine, histidine, tyrosine and tryptophan. The arginine Schiff bases were reported structurally by XRD for the first time. Their guanidinium side chains may offer potential application as thrombin inhibitor. Tyrosine and tryptophan Schiff bases exhibit a series of bilayer-mimicking solid-state structures, stem from the distinctive H-bonding and aromatic stacking interactions. Moreover, the feasibility of these aromatic amino acids (including histidine) to form metal aggregates, coordination polymer and MOF has been proven. Potential applications such as magneto compounds and host-guest reaction are also discussed. While the crystal engineering of small molecules is presented, the next focus of the study emphasizes metalloprotein design. Of particular interest is to tune the redox potential of cupredoxin T1 azurin (Az), by manipulating the interaction beyond primary coordination sphere. Careful introduction of hydrophobicity around histidine ligands by M44F/G116F mutation raises the potential by ~50 mV. Combining this mutation with a reported triple mutant, N47S/F114N/M121L gives a nearly 1V variant, which may be a viable redox agent for oxidation process. Finally, a direct comparison of such secondary effect between T1 Az and CuA Az was attempted. Interestingly, similar mutation on CuA Az (N47S and E114P) exerts only half of the changes that have seen on T1 Az, implying the spread-out effect in the binuclear CuA Az.