Garribba, E.

Coord. Chem. Rev. 2021, 449, 214192, 10.1016/j.ccr.2021.214192

The understanding of the role of vanadium enzymes and of vanadium compounds (VCs) in biology, as well as the design of new vanadium-based species for catalysis, materials science and medicinal chemistry has exponentially increased during the last decades. In biological systems, VCs may rapidly interconvert under physiological conditions and several V-containing moieties may be formed and bind to proteins. These interactions play key roles in the form transported in blood, in the uptake by cells, in inhibition properties and mechanism of action of essential and pharmacologically active V species. In this review, we focus on the recent advances made, namely in the application of the theoretical methodologies that allowed the description of the coordinative and non-covalent VC–protein interactions. The text is organized in six main topics: a general overview of the most important experimental and computational techniques useful to study these systems, a discussion on the nature of binding process, the recent advances on the comprehension of the V-containing natural and artificial enzymes, the interaction of mononuclear VCs with blood and other physiologically relevant proteins, the binding of polyoxidovanadates(V) to proteins and, finally, the biological and therapeutic implications of the interaction of pharmacologically relevant VCs with proteins and enzymes. Recent developments on vanadium-containing nitrogenases, haloperoxidases and nitrate reductases, and binding of VCs to transferrin, albumins, immunoglobulins, hemoglobin, lysozyme, myoglobin, ubiquitin and cytochrome c are discussed. Challenges and ideas about desirable features and potential drawbacks of VCs in biology and medicine and future directions to explore this chemistry area are also presented. The deeper understanding of the interactions of V-species with proteins, and the discussed data may provide the basis to undertake the investigation, design and development of new potentially active VCs with a more solid knowledge to predict their binding to biological receptors at a molecular point of view.

Hasegawa, J.-Y.; Lehnert, N.

J. Am. Chem. Soc. 2017, 139, 17265-17268, 10.1021/jacs.7b10154

Myoglobin reconstituted with iron porphycene catalyzes the cyclopropanation of styrene with ethyl diazoacetate. Compared to native myoglobin, the reconstituted protein significantly accelerates the catalytic reaction and the kcat/Km value is 26-fold enhanced. Mechanistic studies indicate that the reaction of the reconstituted protein with ethyl diazoacetate is 615-fold faster than that of native myoglobin. The metallocarbene species reacts with styrene with the apparent second-order kinetic constant of 28 mM–1 s–1 at 25 °C. Complementary theoretical studies support efficient carbene formation by the reconstituted protein that results from the strong ligand field of the porphycene and fewer intersystem crossing steps relative to the native protein. From these findings, the substitution of the cofactor with an appropriate metal complex serves as an effective way to generate a new biocatalyst.

Kitagawa, S.; Ueno, T.

Chem. - Asian J. 2014, 9, 1373-1378, 10.1002/asia.201301347

Porous protein crystals, which are protein assemblies in the solid state, have been engineered to form catalytic vessels by the incorporation of organometallic complexes. Ruthenium complexes in cross‐linked porous hen egg white lysozyme (HEWL) crystals catalyzed the enantioselective hydrogen‐transfer reduction of acetophenone derivatives. The crystals accelerated the catalytic reaction and gave different enantiomers based on the crystal form (tetragonal or orthorhombic). This method represents a new approach for the construction of bioinorganic catalysts from protein crystals.

Kitagawa, S.; Ueno, T.

Isr. J. Chem. 2015, 55, 40-50, 10.1002/ijch.201400097

Construction of artificial metalloenzymes based on protein assemblies is a promising strategy for the development of new catalysts, because the three‐dimensional nanostructures of proteins with defined individual sizes can be used as molecular platforms that allow the arrangement of catalytic active centers on their surfaces. Protein needles/tubes/fibers are suitable for supporting various functional molecules, including metal complexes, synthetic molecules, metal nanoparticles, and enzymes with high densities and precise locations. Compared with bulk systems, the protein tube‐ and fiber‐based materials have higher activities for catalytic reactions and electron transfer, as well as enhanced functions when used in electronic devices. The natural and synthetic protein tubes and fibers are constructed by self‐assembly of monomer proteins or peptides. For more precise designs of arrangements of metal complexes, we have developed a new conceptual framework, based on the isolation of a robust needle structure from the cell‐puncturing domains of a bacteriophage. The artificial protein needle shows great promise for use in creating efficient catalytic systems by providing the means to arrange the locations of various metal complexes on the protein surface. In this account, we discuss the recent development of protein needle‐based metalloenzymes, and the future developments we are anticipating in this field.