Theoretical investigation of five-coordinated manganese(III) oxophlorin with different axial ligands at various spin states using different DFT methods

The Mn(III)-oxophlorin complexes with imidazole, pyridine and t-butylcyanide as axial ligands have been studied using B3LYP, Bv86p, and M06-2X methods. All of the possible optimized geometries are specified, while the M06-2X is employed. Results obtained show that the isomers of Mn(III)-oxophlorin with imidazole or pyridine are the most stable at quintet state, compared to singlet and triplet spin states. Besides, there are two and four [Formula: see text]-electrons on manganese in each of these complexes at triplet and quintet states, respectively. Also, Mn(III)-oxophlorin with t-butylcyanide as axial ligand is only stable at singlet state. Non-specific solvent effects show that dispersion and London forces have the basic role in stability of complexes in a solvent. Note that latter interactions can occur in medium with dielectric constant ([Formula: see text]) of [Formula: see text]8, such as [Formula: see text] for position of oxophlorin in heme oxygenase enzyme. NBO analysis show that there is no degeneracy between d orbitals of Mn in the five-coordinated Mn(III)-oxophlorin at singlet and triplet spin states, but two d orbitals of manganese are degenerated in latter complexes at quintet state. Such degeneracy of d orbitals is observed in a complex with square pyramid structure. Then five-coordinated Mn(III)-oxophlorin with imidazole or pyridine is the most stable at quintet spin state, because of its geometry corresponding to square pyramid configuration of atoms. Also, nonbounding interaction between Mn and the ring of oxophlorin or Mn and ligand are more effective in Mn(III)-oxophlorin with imidazole as axial ligand, compared to pyridine and t-butylcyanide.

A new regime of heme-dependent aromatic oxygenase superfamily

Two histidine-ligated heme-dependent monooxygenase proteins, TyrH and SfmD, have recently been found to resemble enzymes from the dioxygenase superfamily currently named after tryptophan 2,3-dioxygenase (TDO), that is, the TDO superfamily. These latest findings prompted us to revisit the structure and function of the superfamily. The enzymes in this superfamily share a similar core architecture and a histidine-ligated heme. Their primary functions are to promote O-atom transfer to an aromatic metabolite. TDO and indoleamine 2,3-dioxygenase (IDO), the founding members, promote dioxygenation through a two-step monooxygenation pathway. However, the new members of the superfamily, including PrnB, SfmD, TyrH, and MarE, expand its boundaries and mediate monooxygenation on a broader set of aromatic substrates. We found that the enlarged superfamily contains eight clades of proteins. Overall, this protein group is a more sizeable, structure-based, histidine-ligated heme-dependent, and functionally diverse superfamily for aromatics oxidation. The concept of TDO superfamily or heme-dependent dioxygenase superfamily is no longer appropriate for defining this growing superfamily. Hence, there is a pressing need to redefine it as a heme-dependent aromatic oxygenase (HDAO) superfamily. The revised concept puts HDAO in the context of thiol-ligated heme-based enzymes alongside cytochrome P450 and peroxygenase. It will update what we understand about the choice of heme axial ligand. Hemoproteins may not be as stringent about the type of axial ligand for oxygenation, although thiolate-ligated hemes (P450s and peroxygenases) more frequently catalyze oxygenation reactions. Histidine-ligated hemes found in HDAO enzymes can likewise mediate oxygenation when confronted with a proper substrate.

Axial-Ligand-Cleavable Silicon Phthalocyanines Triggered by Near-Infrared Light toward Design of Photosensitizers for Photoimmunotherapy

Near-infrared photoimmunotherapy (NIR-PIT) is a novel phototherapy for the treatment of cancer that uses NIR light and conjugates of antibody-IR700, a silicon phthalocyanine photosensitizer. A key feature of NIR-PIT is light-induced axial ligand cleavage of IR700, which finally causes cytotoxicity. Here, we focused on protonation of the axial ligand on the IR700 anion radical during the photochemical process. The Gibbs energy in the protonation reaction of IR700 derivatives with different axial ligands was calculated. These calculations suggested the order of the cleavage efficiency corresponds to the basicity of the axial ligand (i.e. alkoxy > siloxy (IR700) > phenoxy ≈ oxycarbonyl), which was confirmed by the photoirradiation experiments with synthesized compounds. Thus, axial ligand cleavage is significantly dependent on the basicity of the axial ligand. Our findings suggest that PIT reagent with an IR700 derivative bearing alkoxy group would show better efficacy than IR700.