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Background


Metallacycles are a large class of cyclic compounds that contain both organic and metallic elements. These can be simple as a six-membered metallabenzene such as stannabenzene. Metallabenzenes were first synthesized in 1982. Metallacycles can also take the form of more complicated structures containing dozens of atoms, one example of which is metallacrowns. Metallacycles are present as intermediates in reactions and can be used as selective molecular traps. One main effect that metallic atom substitution can have on a cyclic carbon compound is changing the geometry. Shown to the right are geometries from ab-initio calculations of benzene (C6H6) and stannabenzene, which is benzene with one carbon atom replaced with tin (SnC5H6).

Geometric Effects of Simple C-Sn Substitution
Ab-initio calculations can be used to theoretically predict molecular geometries. A simple study was performed on theoretical metallacycles by substituting one carbon atom in benzene for other elements in the same group. In benzene, all C-C bond lengths were calculated as 1.39 Å and the internal C-C-C bond angles are all 120°. In stannabenzene, the ring geometry is clearly deformed to be more open. The ring bond lengths range from 1.39 to 2.05 Å, with bond lengths ranging 1.39 to 2.05 Å. This allows for the tuning of internal cavity size for metallocrowns, which is useful for sequestration of heavy alkali metals. This version of stannabenzene has not been produced in laboratory settings, but it is still a useful exercise in studying the geometry change of a cyclic compound when swapping carbon for a metal atom.

Types
There are a wide variety of metallacycles including metallacrowns, metallacryptands, metallahelices, molecular wheels. There are also supramolecular metallacycles, which are composed of aggregates of smaller molecules. Metallacyles can also be seen as reaction intermediates, such as in olefin metathesis.

Metallacrowns
A metallacrown is an inorganic analogue of an organic crown ether. While organic crown ethers are cyclic molecules of carbon and oxygen, metallacrowns contain metals and other heteroatoms, such as nitrogen. Metallacrowns can be prepared with a variety of metals in the ring and in a variety of ring sizes.

Metallacrown nomenclature has been developed in a manner similar to the nomenclature of organic crown ethers, which are named by the total number of atoms in the ring, followed by “C” for “crown,” and the number of oxygen atoms in the ring. For example, 12-crown-4 or 12-C-4 describes Figure 2a. When naming metallacrowns, a similar format is followed. However, the C becomes “MC” for “metallacrown” and the “MC” is followed by the ring metal, other heteroatom, and the ligand used to make the metallacrown. For example, the metallacrown in Figure 2b is named [12-MCFe(III)N(shi)-4], where “shi” is the ligand, salicylhydroxamic acid.

The first metallacrown was synthesized in 1989 by Pecoraro and Lah. The molecule was MnII(OAc)2(DMF)6[12-MCMn(III)N(shi)-4]. Among the interesting features of the metallacrown structure is the remarkable similarity between the cavity size and bite distance in the 12-C-4 and the 12-MC-4. In the 12-C-4, the cavity size is 2.79 Å and the bite distance is 0.6 Å. In the 12-MC-4, the cavity size is 2.67 Å and the bite distance is 0.5 Å.

In recent years, many other metallacrowns have been prepared, including 9-MC-3, 15-MC-5, and 18-MC-6. Ring size is controlled by the ratio of ligand to metal that is used. Common ring metals have included V(III), Mn(III), Fe(III), Ni(II) and Cu(II). The ligand choice also plays some role in the structure. The core of the structure is determined in part by the ligand. Commonly salicylhydroxamic acid and derivatives are used because they contain both N and O in such an orientation that they are able to coordinate metals. The ligand also helps to maintain the structural integrity of the metallacrown.

Metallacrowns form in a self-assembly reaction. They are prepared by dissolving the ligand in a solvent, such as methanol, dimethylformamide, or pyridine. To the solution, a metal salt of the desired ring metal is added. The reaction occurs spontaneously, and upon evaporation of solvent, crystals can be obtained. The structures are characterized by single-crystal X-ray crystallography.

There are many potential applications for this type of metallacycle. For example, 12-MC-4 with Ni(II) or Mn(III) have shown antibacterial activity against a variety of common bacteria. For example, the 12-MCMn(III)-4 is more effective against Staphylococcus aureus and Escherichia coli than the small molecule Mn(II) salts used to treat them. The unique property of the presence of transition metals in these metallacrowns allow for tuning of cavity size and molecular geometry by substituting the transition metal atoms. This suggests the use of these metallacrowns for molecular recognition and selective molecular trapping. Other possibilities are in catalysis and the use of magnetically active metals to create single molecule magnets.

Metallabenzenes
In the 19th century, the discovery of the structure of benzene opened the gate to the fascinating world of aromaticity in the field of chemistry. For decades, chemists have invested significant time and energy on exploring the challenging theoretical and synthesis aspects of the unusual properties of aromatic compounds, including intermediate bond lengths between single and double bonds, unusual 1H NMR chemical shifts (downfield chemical shifts for ring protons ) and higher stability than the canonical form of lowest energy.

Heterocyclic aromatic compounds have drawn special attention from chemists for years as important research branch of aromatic chemistry. Despite their heterogeneity, benzene-like compounds such as pyridine, phosphabenzene, arsabenzene, pyrylium, and thiabenzene still exhibit aromatic properties. Particularly since the beginning of 1980s, leading researchers have begun concentrating on “metallacyclic benzenoid compounds” in which one CH node is replaced by a transition metal and its ligand connections.

In 1979, theoretical metallabenzene models were proposed by Thorn and Hoffmann. Three kinds of postulated compounds were defined as candidates to display delocalized bonding characteristics. Based on their hypothesis, these cyclic metallabenzenes were stabilized by electron donating ligands bound to the metal atom and π-donating groups bound to α or γ carbons on the ring. Based on their theory, C5H5- was treated as a monoanionic ligand which would offer 4 e- from M-C σ bonds to the transition metal center. 6 π electrons in the metallacycle provide the evidence that it obeys the Hückel (4n+2) theory, suggesting aromaticity. Explained by molecular orbital theory, 6 electrons would be bound to carbon fragment π-orbitals and a back bonding orbital formed by one empty carbon π-orbital bonding to a dxz orbital from the metal atom.

Recently, Schleyer revised Bleeke's theory and gave a conclusion that metallabenzenes are less aromatic than benzene. He asserted that there were 8 electrons involved in the molecule but 6 take positions the positions 1π, dyz+2π, dyz-2π, dxz+3π as seen to the left. While two π orbitals (1π, dxz+3π) have Hückel character, the others have Möbius properties; so in this way, the carbon fragments may form a δ bonding or two face-face interactions instead.

The first example of a stable metallabenzene, “osmabenzene”, was reported by Roper and his co-workers in 1982, which is typical model for studying the basic knowledge of metallabenzene. It was synthesized using a direct cyclization reaction involving the thiocarbonyl (CS) ligand in precursor A and two ethyne molecules, as shown to the right. Important derivants of osmabenzene can be synthesized by direct protonation, methylation or treatment by carbon monoxide plus following protonation, methylation. Osmabenzene is air-stable as a solid or in solution. The planar metallacyle shows apparent electron density delocation at the carbon ring. The two Os-C bonds are 2.00 Å (1.40 Å for benzene), in the range of Os-C double bond and single bond. In addition, the ring protons are shifted downfield in the 1H NMR, which is believed to be caused by aromatic ring current effects but the magnetic anisotropic influences of large metal atom.

According to the explanation of Bleeke, the osmabenzene and its derivants can be regarded as an Os(II)≡d6 octahedral complex which fits Thorn and Hoffmann’s theory very well. Clearly, these compounds possess ligands PPh3 bonded to the transition metal atom, acting as good electron donors and stabilizing the coordination structure. Furthermore, the sulfur atom connected to α carbon on the ring would also play a positive part as a π donating bonding radical.

Supramolecular Metallacycles
Supramolecular metallacycles are large aggregate molecules designed with angular and linear pieces to form geometric shapes. Common metallacycle shapes in these types of applications include triangles, squares, and pentagons. Each piece contains a specific grouping of atoms, called functional groups, which react with functional groups on other connective pieces. These connective pieces have the ability to self-assemble into the correct shapes when combined in the necessary proportions. These large molecules may improve the ability of chemists to detect molecules of interest in different systems (chemical sensing) and streamline complicated syntheses by exploiting the structure of the metallacycle (catalysis). Both of these applications work towards the goal of mimicking enzyme behavior.

Reaction Intermediates


While there are many reactions that proceed through a metallacycle intermediate, the most well known example is the metallacyclobutane intermediate in the olefin metathesis reaction. Olefin metathesis is a class of reactions in organic chemistry that is used to make new molecules by the catalytic reaction of carbon-carbon double bonds. The reaction is not seen in nature and requires a transition metal catalyst in order to occur. The reaction was discovered in the 1950s; however, the mechanism was not understood. It was proposed by Chauvin and Hérrison in 1970 that the metal carbene catalyst forms a metallacylobutane intermediate and goes through two cycles to regenerate the catalyst. This mechanism is widely accepted, largely due to the work done by Shrock and Grubbs. As a result, Chauvin, Schrock, and Grubbs were awarded the 2005 Nobel Prize in Chemistry.

The Chauvin mechanism, shown in the figure, begins with one alkene which attacks the electropositive carbon of the metal carbene catalyst. In this first step, the metallacyclobutane intermediate forms. The next step is also occurs in one step. In this step, a new olefin forms that contains parts from the original olefin and the catalyst. In order to reform the catalyst, another molecule of the original olefin is introduced. Following the same sequence of events, the new catalyst exchanges its substituents with substituents on the olefin. The result is two molecules of a new olefins and regenerates the catalyst.

While Chauvin proposed this mechanism, it was the work of Schrock and Grubbs that contributed to growth of research in this area. In particular, Schrock and Grubbs developed catalysts for olefin metathesis. Catalysts must be well-defined, stable, and have high selectivity. It is also convenient for catalysts to be stable in the presence of air and moisture. While at DuPont, Schrock attempted to make tantalum complexes. While trying to prepare Ta[CH2C(CH3)]5, he made Ta[CH2C(CH3)]3[=CHC(CH3)3]. This molecule showed no catalytic activity. However, the introduction of alkoxide ligands to the complex increased catalytic activity. Schrock's work in triple bond metathesis showed metal in the catalyst must be very electrophilic and alkoxide ligands should be sterically hindered to be effective. Using a tungsten catalyst, Schrock observed a pseudo-trigonal bipyramidal metallocyclobutane intermediate. This work helped to validate the Chauvin mechanism for olefin metathesis. Since the 1990s, Schrock has made significant progress in developing catalysts using molybdenum and tungsten.

Grubbs developed Grubb's catalyst in 1992. It is a particularly attractive catalyst because it is stable in air, in the presence of water and alcohols, and has very high selectivity. In 1995, the first generation Grubb's catalyst was available and in 1999 the second generation catalyst was developed. The second generation catalyst is efficient in ring closing reactions.

Preparation
Metallacycles are often formed via self-assembly reactions, by which molecules rearrange into a thermodynamically stable supramolecular compound by delicately balancing the enthalpic and entropic effects of forming certain metallacycles. Upon formation, these molecules can self-correct mistakes to induce more stability. The self-assembly of metallacycles is also controlled kinetically. Reaction kinetics are determined by the activation barrier for each step in the reaction. Kinetically limited processes will follow reaction pathways with lower activation barriers. If there are high activation barriers for the thermodynamically favorable product, the reaction can follow a different pathway that leads to a non-thermodynamically favorable product. Metallacycles generally produce the most thermodynamically favorable product - smaller metallacycles form because the larger metallacycles have a higher entropy than smaller metallacycles, despite having more stable internal chemical bonds.

Characterization
One main method of metallacycle characterization is X-ray crystallography. This allows the determination of extremely complicated 3-dimensional structures, such as those present in metallacrowns. Despite bringing extremely detailed information about the structure, this method requires crystallization of the metallacycle. Other methods that have been used to study metallacycles include nuclear magnetic resonance (NMR) and mass spectrometry. NMR is useful in determining the chemical shifts of atoms to study the equivalence of different atoms in the metallacycle and can hint at the overall structure and aromaticity, while mass spectroscopy can be used to study the fragments of a larger metallacycle, illuminating the simple building blocks.