Periodic Reporting for period 2 - MUSYCA (MUltimetallic SYstems for C-H Activation processes)
Periodo di rendicontazione: 2021-08-01 al 2022-07-31
One of the most crucial challenges for society in the 21st century is finding renewable sources of energy. Apart from abandoning fossil fuels, this would help diminishing pollution by lowering the levels of greenhouse gases like carbon dioxide (CO2) or methane (CH4). If we were able to transform methane (around 84 times more potent than CO2 as a greenhouse gas) in a controlled and selective manner, we would be able to use a pollutant as a source of carbon and energy. In fact, this is what some organisms called methanotrophic bacteria do. However, this is still not possible for us to achieve nowadays. The way these organisms transform CH4 into different hydrocarbons relies on some proteins called methane monooxygenase (MMO) enzymes, which possess two metal atoms in the place where methane transformation takes place (dinuclear active sites). These two metals are in close proximity and surrounded by organic fragments from amino acid residues, hence they can all cooperate to carry out the chemical transformation of interest. There are different types of these MMO proteins, depending on the metals: dicopper or diiron methane-transforming enzymes can be found in nature. However, nature has developed this mechanism due to thousands of years of evolution.
In our case, we need to speed up this process by making molecular models of these proteins in the laboratory. Through chemical synthesis, we can mimic the active sites of these enzymes by making analogues of the amino acid chains that hold the metals close together in the active site. These analogues are called ‘ligands’, and they are usually organic fragments that can be made in the lab in a short number of synthetic steps from commercially available reagents. The combination of rational ligand design and chemical synthetic methods is a powerful strategy to achieve this goal, since chemical modification of the ligands has a dramatic impact on the structure/activity relationship of the resulting bimetallic complexes.
Related to CH4 transformation, catalytic C-H activation is one of the most active areas of chemistry nowadays, given that selective functionalization of C-H bonds gives rise to a wide range of products that we use in our everyday lives. Particularly, C-H borylation (transformation of a C-H bond into a C-B bond) is an instrumental process in fields like carbohydrate analysis, novel materials or therapeutic agents, to name a few. In the latter case, the ability to selectively fuse organoboron species with other organic fragments via cross-coupling reactions is one of the main strategies employed in the pharmacological industry for the synthesis of new drugs. The utilization of copper-based catalysts in borylation reactions is an attractive methodology due to the low cost of the metal and the generally mild conditions required for these reactions to take place. In these processes, copper(I) boryl species have been invoked as reactive intermediates, but they are extremely challenging to isolate and study (they tend to decompose in solution releasing elemental copper). If we could synthesize, stabilize and isolate these compounds, we would be able to understand and modulate their properties so that we can design catalysts with better properties in terms of activity and/or selectivity.
In this project, the utilization of dinucleating 1,8-naphthyridine-based ligands has allowed us to synthesize a series of dicopper complexes, among which we can find dicopper(I) mu-boryl complexes which exhibit remarkable thermal stability (see next section). Additionally, structural models of some of the previously mentioned enzymes have been succesfully achieved with the synthesis of iron-containing homo- and heterobimetallic complexes stabilized by naphthyridine-based scaffolds.
In our case, we need to speed up this process by making molecular models of these proteins in the laboratory. Through chemical synthesis, we can mimic the active sites of these enzymes by making analogues of the amino acid chains that hold the metals close together in the active site. These analogues are called ‘ligands’, and they are usually organic fragments that can be made in the lab in a short number of synthetic steps from commercially available reagents. The combination of rational ligand design and chemical synthetic methods is a powerful strategy to achieve this goal, since chemical modification of the ligands has a dramatic impact on the structure/activity relationship of the resulting bimetallic complexes.
Related to CH4 transformation, catalytic C-H activation is one of the most active areas of chemistry nowadays, given that selective functionalization of C-H bonds gives rise to a wide range of products that we use in our everyday lives. Particularly, C-H borylation (transformation of a C-H bond into a C-B bond) is an instrumental process in fields like carbohydrate analysis, novel materials or therapeutic agents, to name a few. In the latter case, the ability to selectively fuse organoboron species with other organic fragments via cross-coupling reactions is one of the main strategies employed in the pharmacological industry for the synthesis of new drugs. The utilization of copper-based catalysts in borylation reactions is an attractive methodology due to the low cost of the metal and the generally mild conditions required for these reactions to take place. In these processes, copper(I) boryl species have been invoked as reactive intermediates, but they are extremely challenging to isolate and study (they tend to decompose in solution releasing elemental copper). If we could synthesize, stabilize and isolate these compounds, we would be able to understand and modulate their properties so that we can design catalysts with better properties in terms of activity and/or selectivity.
In this project, the utilization of dinucleating 1,8-naphthyridine-based ligands has allowed us to synthesize a series of dicopper complexes, among which we can find dicopper(I) mu-boryl complexes which exhibit remarkable thermal stability (see next section). Additionally, structural models of some of the previously mentioned enzymes have been succesfully achieved with the synthesis of iron-containing homo- and heterobimetallic complexes stabilized by naphthyridine-based scaffolds.
The goal of this project is to use 1,8-naphthyridine as ligand for the assembly of these molecular models. The naphthyridine scaffold is composed of two fused pyridine rings, which holds two metals in close contact via coordination through the nitrogen atoms. Additionally, the naphthyridine framework can be further functionalized to introduce chelating side-arms at the 2- and 7- positions of the ring. Thus, different ligands resembling amino acid residues can be used to surround the metals. In fact, new dinucleating ligands have been made in the lab, and they have proven effective in the synthesis and characterization of new dicopper and diiron homobimetallic complexes, since they are able to support both metal atoms with metal-metal distances around 2.3 to 3.3 angstroms. Additionally, these naphthyridine-based ligands has allowed us to selectively synthesize heterobimetallic complexes containing Fe and Mn inside the coordination pocket, similar to enzymes such as purple acid phosphatase or ribonucleotide reductase. The identity of the heterobimetallic species has been elucidated by a combination of NMR, Mass Spectrometry and X-Ray diffraction techniques, confirming their role as structural models for the active sites of the aforementioned enzymes. Moreover, the naphthyridine-dicopper scaffold opened the door to the isolation and study of elusive reactive intermediates widely proposed in homogeneous catalysis such as dicopper(I) boryl complexes. These compounds can mediate C-H activation of terminal alkynes and, unlike previous examples in the literature (usually made at low temperatures in apolar solvents), they exhibit remarkable thermal stability (they are completely stable for days in polar solvents at temperatures up to 100 ºC). A number of experimental and computational tools were utilized to investigate the reason behind this unexpected robustness, and they seem to point to the dinucleating character of the utilized ligands as one of the main sources for their stability. Therefore, these studies highlight the paramount importance of ligand design in the synthesis of structural or catalytic molecular models.
The results obtained from this project have been disseminated in the form of scientific papers (Chem. Sci. 2022), national (XIIIth International School on Organometallic Chemistry Marcial Moreno Mañas, Spain) and international (29th International Conference on Organometallic Chemistry, Czech Republic) conferences.
The results obtained from this project have been disseminated in the form of scientific papers (Chem. Sci. 2022), national (XIIIth International School on Organometallic Chemistry Marcial Moreno Mañas, Spain) and international (29th International Conference on Organometallic Chemistry, Czech Republic) conferences.
The utilization of these new dinucleating ligands have made possible the selective formation of homo- and heterobimetallic transition metal complexes, allowing their future study in C-H oxidation reactions. These results are relevant, as previously demonstrated by our group, since the chemistry of bimetallic complexes is rather recent compared to that of monometallic analogues. If the last century witnessed a revolution in industry due to catalysis carried out by monometallic complexes (Ziegler-Natta polymerization gave rise to the plastics industry, asymmetric hydrogenation allowed the industrial synthesis of a large amount of drugs like L-Dopa, olefin metathesis and cross-coupling reactions changed the paradigm in organic synthesis…), there is no doubt that the chemistry of bimetallic and multinuclear complexes will be key in the chemical problems society is facing this century.