Positive Charge on Porphyrin Ligand and Nature of Metal Center Define Basic Physicochemical Properties of Cationic Manganese and Iron Porphyrins in Aqueous Solution

Abstract

Recently, comprehensive studies on positively charged manganese porphyrins show that these compounds, known for their superoxide dismutase (SOD) mimetic ability, can be equally reactive toward a broad array of other redox active molecules of biological relevance present in a cellular milieu. In this context, the examination of some fundamental aspects of physicochemical behavior of metalloporphyrins behind their rich aqueous chemistry is believed to provide a valuable basis for the understanding of newly observed biological effects of these compounds in vivo and throw more light on a potential use of common SOD porphyrin mimetics for other redox active cellular targets in order to earn desirable therapeutic effects. Herein, we present versatile characteristics of highly positively charged Mn­(P) and Fe­(P) porphyrins (with up to +9 and +8 overall charge, respectively) with regard to their acid–base equilibria, metal coordination sphere, water-exchange dynamics, redox properties, and substitution behavior toward selected ligands. For the purpose of these comparative studies, we synthesized for the first time a 9-fold cationic manganese­(III) porphyrin. The findings reported in this study enabled highlighting the most important similarities and differences characterizing the aqueous chemistry of positively charged manganese and iron porphyrins and, therefore, outlining the potential factors which can affect the intimate underlying mechanism behind the redox cycling of these metalloporphyrins.

Cobalt(II), Zinc(II), Iron(III), and Copper(II) Complexes Bearing Positively Charged Quaternary Ammonium Functionalities: Synthesis, Characterization, Electrochemical Behavior, and SOD Activity

“…This can be explained by the fact that there is no electronic communication between these positive residues and the metal center, because they are not conjugated and spatial distribution of charged groups in the PBP coordination sphere around Fe(III) or Fe(II), respectively, seems not to support required interactions. The same behavior we have observed in the case of highly positively charged Fe and Mn porphyrins . Although the redox potential remains unchanged, different from [Fe(dapsox)(H 2 O) 2 ]ClO 4 the complex 3 does not exhibit SOD activity, demonstrating that the formal redox potential is not the only criteria for a metal complex to be an SOD mimetic.…”

“…This might be the reason for the lack of the catalytic activity of 3 , where positively charge residues could contribute to increased stabilization of the putative Fe(III)‐peroxo and/or slow down its deprotonation. We have previously shown that increase of a positive charge on the porphyrin ring does not necessary influences corresponding redox potential of the Fe center, but it strongly influences its kinetic behavior …”

All Four Atropisomers of Iron Tetra(o-N,N,N-trimethylanilinium)porphyrin in Both the Ferric and Ferrous States

“…Traditionally, charged groups have been added to macrocyclic ligand designs to improve solubility, especially solubility in aqueous solutions. , Pyridinium-, carboxylate-, and sulfonate-derivatized macrocycles are the most common examples of these designs, where solubility is controlled, at least in part, by the pH of the solution. Alkylated pyridinium and ammonium functional groups offer a more permanent form of charge installation and have been used in porphyrin designs to facilitate aqueous O 2 /CO binding and superoxide dismutase studies. − There are a few examples of highly charged ligand designs (8+/8−) affecting basic physicochemical properties of metalloporphyrins, but these studies have only probed charge-symmetric systems in aqueous solvents. − There are no prior systems insofar as we can find that analyze metal–macrocycles with different asymmetric charge distributions in nonaqueous solvents …”

Metalloporphyrins in Medicine: From History to Recent Trends

“…Over the time, versatile physical and catalytic MeP properties have promoted their application in other fields of medicine. Currently, MeP are investigated as mimetics of biologically active compounds, immunoactivators/suppressors, ROS producers/protectors, specific inhibitors, etc ., with great prospect in diagnostics and treatment. , …”

“…Currently, MeP are investigated as mimetics of biologically active compounds, immunoactivators/suppressors, ROS producers/protectors, specific inhibitors, etc., with great prospect in diagnostics and treatment. 45,46 2.1. Photodynamic Therapy.…”