Bioinorganic chemistry, biomimetic catalysis and selective oxidation of alkanes, including methane, supramolecular catalysis, cavitins, metallocavitins.

1. Detection of the reaction of carbenes with N₂ with the formation of diazocompounds;

2. Discovery of methane activation on platinum complexes, which initiated the development of the entire field of metal–complex activation of alkanes (State Diploma for discovery No. 284);

3. The first demonstration of the heterolytic terminal mechanism of O₂ activation on porphyrin iron complexes - cytochrome P-450 models;

4. The first evidence of a two–electron (ferryl) mechanism for the oxidation of alkanes by binuclear iron complexes - models of non-heme oxygenases;

5. An early hypothesis of a bridging homolytic mechanism of O₂ activation in the active center of soluble methanmonooxygenase, s-MMO, which has received experimental confirmation.

1. Bioinspired Oxidation of Methane: From Academic Models of Methane Monooxygenases to Direct Conversion of Methane to Methanol. A. A. Shteinman. Kinetics and Catalysis, 2020, 61(3), 339–359; Биоинспирированное окисление метана: от академических моделей метанмонооксигеназ к процессу прямого получения метанола. А. А. Штейнман. Кинетика и катализ 2020, 61(3), 312-333.

2. Nonheme mono- and dinuclear iron complexes in bio-inspired C–H bond hydroxylation reactions: Mechanistic insight.  Аlbert A. Shteinman, Mainak Mitra. Inorganica Chimica Acta 523 (2021) 120388.

3. Metallocavitins as Promising Industrial Catalysts: Recent Advances. Albert A. Shteinman. Frontiers in Chemistry 2022, 9, 806800.

4. Metallocavitins as Emerging Bioinspired Catalysts. Albert A. Shteinman, In book: Progress in Chemical Science Research Vol. 4, Ch. 8. DOI: 10.9734/bpi/pcsr/v4/7603F

5.  Metallocavitins as Advanced Enzyme Mimics and Promising Chemical Catalysts. Albert A. Shteinman, Catalysts 2023, 13, 415. https://doi.org/10.3390/catal13020415

Annotation to the reviews [1]-[5].

Cavitins are an extensive and growing class of molecules and supramolecular ensembles with their inherent nanoporosity, which is becoming increasingly important in enzyme modeling and catalysis. The supramolecular approach is becoming dominant in biomimetics and chemical catalysis. Enzymes are natural cavitins. The enzymatic "pocket" is a hydrophobic cavity in the structure of the enzyme, which plays a key role in the high organization of their active centers and diverse functionality. The mechanism of functioning of enzymes is complex and far from being fully understood. Enzymes are extremely powerful catalysts for various reactions with excellent activity under mild conditions and exceptional substrate specificity and product selectivity. Metalloenzymes constitute the dominant and important group of biocatalysts in the processes of vital activity of all organisms. The enzymatic pocket controls the nuclearity of the metallocenter, the selective binding of substrates and reagents and their pre-organization into a pre-reaction associate with the metallocenter.

Understanding the chemistry within an enzymatic nanocavity due to the confinement effect requires the use of relatively simple model systems. The biomimetic strategy for a long time has been mainly focused on the first coordination sphere of the metal ion, taking into account only the ligands directly associated with the metal. However, in order to protect the metal center from undesirable pathways, to activate or stabilize intermediate active forms, cavitins have become increasingly important in the last decade, because they provides a well-defined second coordination sphere of ligands that are not directly related to the metal. These ligands are fixed on the inner surface of the hydrophobic cavity of the enzyme and participate in the formation of the active center of M-cavitin. Chemical cavitins appeared thanks to the efforts of synthetic and supramolecular chemists. On the other hand, it is known that the efficiency of catalysts based on transition metals increases due to their inclusion in the cavities of molecular nanocontainers, such as microporous compounds, charcoal or zeolites, which have long been successfully used in industrial heterogeneous catalysis, and this also stimulates interest in metallocavitins.

The simplicity of the synthesis of cavitins has led to a rich library of their architectures, ranging from discrete monocavitins such as cyclodextrins, crown esters, cyclophanes, cryptophanes, capsules, cavitands, and expanded polycavitins such as zeolites, MOF, COF, porous polymers, etc. Over the years, the complexity of cavitins has increased dramatically. However, there remains a significant gap between structural modeling and catalytic activity in these artificial systems.

Molecules encorporated in nanocavity can radically change their chemical and physical properties compared to molecules in solution due to various cavity effects. These effects change the typical reaction pathway, turning on and off individual stages, that leads to unusual selectivity or induces stereoselectivity due to an asymmetric cavity. The most important for the reaction rate are the proximity and orientation of the substrates, as well as the stabilization of the transition state.

M-cavitins opened up the possibility for chemistry to use many principles developed in nature during evolution, expanded the tools of organic chemistry and proved to be extremely important in fine organic synthesis and pharmaceutical chemistry, especially for enantioselective reactions. M-cavitins demonstrate high activity in energetically problematic reactions involving small molecules and high selectivity of these reactions in relation to valuable products. Great challenges for these molecules remain in the search for environmentally friendly photocatalytic or electrochemical energy conversion using such accessible and inexhaustible clean materials as water and carbon dioxide, as well as selective oxidation of strong sp³ C-H bonds, including the oxidation of methane to methanol with molecular oxygen or hydrogen peroxide in the water.

The problem of soft selective oxidation of inert alkanes - methane and its closest homologues - has occupied the minds of chemists for more than a century. Although now, as a result of the efforts of several generations of scientists, quite encouraging results have been achieved, some important issues remain unresolved. The study of bioinspired oxidation of alkanes since the middle of the 20th century allowed, on the one hand, to come closer to understanding the mechanism of enzymatic oxidation of methane by oxygenases, on the other hand, to enrich chemistry with new synthetic reactions already implemented in the case of heme oxygenase - cytochrome P450, and non-heme mononuclear oxygenases. The object of chemical modeling currently remains the less studied binuclear methane monooxygenases of microorganisms: iron-containing sMMO and copper-containing pMMO.

It can also be noted that cavitins are increasingly being used in various fields from material chemistry and catalysis to medicine.