Organometallic chemistry is the study of chemical compounds containing bonds between carbon and a metal.Since many compounds without such bonds are chemically similar, an alternative may be compounds containing metal-element bonds of a largely covalent character. Organometallic chemistry combines aspects of inorganic chemistry and organic chemistry.
Organometallic compounds are also known as organo-inorganics, metallo-organics and metalorganics. Organometallic compounds are distinguished by the prefix "organo-" e.g. organopalladium compounds. Examples of such organometallic compounds include all Gilman Reagents, which contain lithium and copper. Tetracarbonyl nickel, and ferrocene are examples of organometallic compounds containing transition metals. Other examples include organomagnesium compounds like iodo(methyl)magnesium MeMgI, diethylmagnesium (Et2Mg), and all Grignard reagents; organolithium compounds such as butyllithium (BuLi), organozinc compounds such as chloro(ethoxycarbonylmethyl)zinc (ClZnCH2C(=O)OEt); and organocopper compounds such as lithium dimethylcuprate (Li+[CuMe2]–).
In addition to the traditional metals, lanthanides, actinides, and semimetals, elements such as boron, silicon, arsenic, and selenium are considered to form organometallic compounds, e.g. organoborane compounds such as triethylborane (Et3B).
Structure and properties
The metal-carbon bond in organometallic compounds is generally of character intermediate between ionic and covalent. Primarily ionic metal-carbon bonds are encountered either when the metal is very electropositive (as in the case of the alkali metals) or when the carbon-containing ligand exists as a stable carbanion. Carbanions can be stabilized by resonance (as in the case of the aromatic cyclopentadienyl anion) or by the presence of electron-withdrawing substituents (as in the case of the triphenylmethyl anion). Hence, the bonding in compounds like sodium acetylide and triphenylmethylpotassium is primarily ionic. On the other hand, the ionic character of metal-carbon bonds in the organometallic compounds of transition metals, poor metals, and metalloids tends to be intermediate, owing to the middle-of-the-road electronegativity of such metals.
Organometallic compounds with bonds that have characters in between ionic and covalent are very important in industry, as they are both relatively stable in solutions and relatively ionic to undergo reactions. Two important classes are organolithium and Grignard reagents. In certain organometallic compounds such as ferrocene or dibenzenechromium, the pi orbitaStructure and properties.
Organometallic compounds undergo several important reactions:
oxidative addition and reductive elimination
transmetalation
carbometalation
Hydrometalation
electron transfer
beta-hydride elimination
organometallic substitution reaction
carbon-hydrogen bond activation
cyclometalation
Migratory insertion
Tuesday, September 29, 2009
Thursday, September 17, 2009
Fullerene chemistry
Fullerene chemistry is a field of organic chemistry devoted to the chemical properties of fullerenes.Research in this field is driven by the need to functionalize fullerenes and tune their properties. For example fullerene is notoriously insoluble and adding a suitable group can enhance solubility. By adding a polymerizable group, a fullerene polymer can be obtained. Functionalized fullerenes are divided into two classes:
exohedral with substituents outside the cage
endohedral fullerenes with trapped molecules inside the cage.
Chemical properties of fullerenes.
Fullerene or C60 is soccer-ball-shaped or Ih with 12 pentagons and 20 hexagons. According to Euler's theorem these 12 pentagons are required for closure of the carbon network consisting of n hexagons and C60 is the first stable fullerene because it is the smallest possible to obey this rule. In this structure none of the pentagons make contact with each other. Both C60 and its relative C70 obey this so-called isolated pentagon rule (IPR). The next homologue C84 has 24 IPR isomers of which several are isolated and another 51,568 non-IPR isomers. Non-IPR fullerenes have thus far only been isolated as endohedral fullerenes such as Tb3N@C84 with two fused pentagons at the apex of an egg-shaped cage
Because of the molecule's spherical shape the carbon atoms are highly pyramidalized, which has far-reaching consequences for reactivity. It is estimated that strain energy constitutes 80% of the heat of formation. The conjugated carbon atoms respond to deviation from planarity by orbital rehybridization of the sp² orbitals and pi orbitals to a sp2.27 orbital with a gain in p-character. The p lobes extend further outside the surface than they do into the interior of the sphere and this is one of the reasons a fullerene is electronegative. The other reason is that the empty low-lying pi* orbitals also have high s character.
The double bonds in fullerene are not all the same. Two groups can be identified: 30 so-called [6,6] double bonds connect two hexagons and 60 [5,6] bonds connect a hexagon and a pentagon. Of the two the [6,6] bonds are shorter with more double-bond character and therefore a hexagon is often represented as a cyclohexatriene and a pentagon as a pentalene or [5]radialene.
Fullerene reactions
Fullerenes tend to react as electrophiles. An additional driving force is relief of strain when double bonds become saturated. Key in this type of reaction is the level of functionalization i.e. monoaddition or multiple additions and in case of multiple additions their topological relationships (new substituents huddled together or evenly spaced).
Fullerenes react as electrophiles with a host of nucleophiles in nucleophilic additions. The intermediary formed carbanion is captured an electrophile. Examples of nucleophiles are Grignard reagents and organolithium reagents. For example the reaction of C60 with methylmagnesium chloride stops quantitatively at the penta-adduct with the methyl groups centered around a cyclopentadienyl anion which is subsequently protonated [5]. Another nucleophilic reaction is the Bingel reaction.
Fullerene reacts with chlorobenzene and aluminium chloride in a Friedel-Crafts alkylation type reaction. In this hydroarylation the reaction product is the 1,2-addition adduct (Ar-CC-H) [6].
The [6,6] bonds of fullerenes react as dienes or dienophiles in cycloadditions for instance Diels-Alder reactions. 4-membered rings can be obtained by [2+2]cycloadditions for instance with benzyne. An example of a 1,3-dipolar cycloaddition to a 5-membered ring is the Prato reaction.
Fullerenes are easily hydrogenated by several methods with C60H18 and C60H36 being most studied hydrofullerenes[citation needed]. However, completely hydrogenated C60H60 is only hypothetical because of large strain. Highly hydrogenated fullerenes are not stable, prolonged hydrogenation of fullerenes by direct reaction with hydrogen gas at high temperature conditions results in collapse of cage structure with formation of polycyclic aromatic hydrocarbons.
Although more difficult than reduction, oxidation of fullerene is possible for instance with oxygen and osmium tetraoxide
Fullerenes react in electrophilic additions as well. The reaction with bromine can add up to 24 bromine atoms to the sphere. The record holder for fluorine addition is C60F48. According to in silico predictions the as yet elusive C60F60 may have some of the fluorine atoms in endo positions (pointing inwards) and may resemble a tube more than it does a sphere [7]
Fullerenes react with carbenes to methanofullerenes
exohedral with substituents outside the cage
endohedral fullerenes with trapped molecules inside the cage.
Chemical properties of fullerenes.
Fullerene or C60 is soccer-ball-shaped or Ih with 12 pentagons and 20 hexagons. According to Euler's theorem these 12 pentagons are required for closure of the carbon network consisting of n hexagons and C60 is the first stable fullerene because it is the smallest possible to obey this rule. In this structure none of the pentagons make contact with each other. Both C60 and its relative C70 obey this so-called isolated pentagon rule (IPR). The next homologue C84 has 24 IPR isomers of which several are isolated and another 51,568 non-IPR isomers. Non-IPR fullerenes have thus far only been isolated as endohedral fullerenes such as Tb3N@C84 with two fused pentagons at the apex of an egg-shaped cage
Because of the molecule's spherical shape the carbon atoms are highly pyramidalized, which has far-reaching consequences for reactivity. It is estimated that strain energy constitutes 80% of the heat of formation. The conjugated carbon atoms respond to deviation from planarity by orbital rehybridization of the sp² orbitals and pi orbitals to a sp2.27 orbital with a gain in p-character. The p lobes extend further outside the surface than they do into the interior of the sphere and this is one of the reasons a fullerene is electronegative. The other reason is that the empty low-lying pi* orbitals also have high s character.
The double bonds in fullerene are not all the same. Two groups can be identified: 30 so-called [6,6] double bonds connect two hexagons and 60 [5,6] bonds connect a hexagon and a pentagon. Of the two the [6,6] bonds are shorter with more double-bond character and therefore a hexagon is often represented as a cyclohexatriene and a pentagon as a pentalene or [5]radialene.
Fullerene reactions
Fullerenes tend to react as electrophiles. An additional driving force is relief of strain when double bonds become saturated. Key in this type of reaction is the level of functionalization i.e. monoaddition or multiple additions and in case of multiple additions their topological relationships (new substituents huddled together or evenly spaced).
Fullerenes react as electrophiles with a host of nucleophiles in nucleophilic additions. The intermediary formed carbanion is captured an electrophile. Examples of nucleophiles are Grignard reagents and organolithium reagents. For example the reaction of C60 with methylmagnesium chloride stops quantitatively at the penta-adduct with the methyl groups centered around a cyclopentadienyl anion which is subsequently protonated [5]. Another nucleophilic reaction is the Bingel reaction.
Fullerene reacts with chlorobenzene and aluminium chloride in a Friedel-Crafts alkylation type reaction. In this hydroarylation the reaction product is the 1,2-addition adduct (Ar-CC-H) [6].
The [6,6] bonds of fullerenes react as dienes or dienophiles in cycloadditions for instance Diels-Alder reactions. 4-membered rings can be obtained by [2+2]cycloadditions for instance with benzyne. An example of a 1,3-dipolar cycloaddition to a 5-membered ring is the Prato reaction.
Fullerenes are easily hydrogenated by several methods with C60H18 and C60H36 being most studied hydrofullerenes[citation needed]. However, completely hydrogenated C60H60 is only hypothetical because of large strain. Highly hydrogenated fullerenes are not stable, prolonged hydrogenation of fullerenes by direct reaction with hydrogen gas at high temperature conditions results in collapse of cage structure with formation of polycyclic aromatic hydrocarbons.
Although more difficult than reduction, oxidation of fullerene is possible for instance with oxygen and osmium tetraoxide
Fullerenes react in electrophilic additions as well. The reaction with bromine can add up to 24 bromine atoms to the sphere. The record holder for fluorine addition is C60F48. According to in silico predictions the as yet elusive C60F60 may have some of the fluorine atoms in endo positions (pointing inwards) and may resemble a tube more than it does a sphere [7]
Fullerenes react with carbenes to methanofullerenes
Saturday, September 12, 2009
Chemistry: Combinatorial chemistry
Combinatorial chemistry
Combinatorial chemistry is a technique by which large numbers of structurally distinct molecules may be synthesised in a time and submitted for pharmacological assay. The key of combinatorial chemistry is that a large range of analogues is synthesised using the same reaction conditions, the same reaction vessels. In this way, the chemist can synthesise many hundreds or thousands of compounds in one time instead of preparing only a few by simple methodology.Combinatorial chemistry involves the rapid synthesis or the computer simulation of a large number of different but structurally related molecules or materials
Synthesis of molecules in a combinatorial fashion can quickly lead to large numbers of molecules. For example, a molecule with three points of diversity (R1, R2, and R3) can generate NR1*NR2*NR3 possible structures, where NR1 ,NR2 , and NR3 are the number of different substituents utilized.
Although combinatorial chemistry has only really been taken up by industry since the 1990s, its roots can be seen as far back as the 1960s when a researcher at Rockefeller University, Bruce Merrifield, started investigating the solid-phase synthesis of peptides. Professor Pieczenik, a colleague of Nobel Laureate Merrifield synthesized the first combinatorial library. In the 1980s researcher H. Mario Geysen developed this technique further, creating arrays of different peptides on separate supports but not a combinatorial library based on random synthesis.
In its modern form, combinatorial chemistry has probably had its biggest impact in the pharmaceutical industry. Researchers attempting to optimize the activity profile of a compound create a 'library' of many different but related compounds. Advances in robotics have led to an industrial approach to combinatorial synthesis, enabling companies to routinely produce over 100,000 new and unique compounds per year.
In order to handle the vast number of structural possibilities, researchers often create a 'virtual library', a computational enumeration of all possible structures of a given pharmacophore with all available reactants. Such a library can consist of thousands to millions of 'virtual' compounds. The researcher will select a subset of the 'virtual library' for actual synthesis, based upon various calculations and criteria.
Combinatorial chemistry is one of the important new methodologies developed by researchers in the pharmaceutical industry to reduce the time and costs associated with producing effective and competitive new drugs.
By accelerating the process of chemical synthesis, this method is having a profound effect on all branches of chemistry, but especially on drug discovery. Through the rapidly evolving technology of combi-chemistry, it is now possible to produce compound libraries to screen for novel bioactivities. This powerful new technology has begun to help pharmaceutical companies to find new drug candidates quickly, save significant money in preclinical development costs and ultimately change their fundamental approach to drug discovery.
Development of Combinatorial Chemistry
---------------------------------------------------------------------------
From a historical perspective, the research efforts made in classical combinatorial chemistry can be briefly outlined in three phases:
In the early 1990s, the initial efforts in the combinatorial chemistry arena were driven by the improvements made in high-throughput screening (HTS) technologies. This led to a demand for access to a large set of compounds for biological screening.
To keep up with this growing demand, chemists were under constant pressure to produce compounds in vast numbers for screening purposes. For practical reasons, the molecules in the first phase were simple peptides (or peptide-like) and lacked the structural complexity commonly found in modern organic synthesis literature.
The second phase started in the late 1990s, when chemists became aware that it is not just about numbers; but something was missing in compounds produced in a combinatorial fashion. Emphasis was thus shifted towards quality rather than quantity.
Like the first phase, the third phase had its origin in progress made by the biomedical community. As the scientific community moved into the post-genomic chemical biology age, there was a growing demand in understanding the role of newly discovered proteins and their interactions with other bio-macromolecules (i.e. other proteins and DNA or RNA). For example, the early goals of the biomedical research community were centered on the identification of small-molecule ligands for biological targets, such as G-protein-coupled receptors (GPCRs) and enzymes.
However, the current challenges are moving in the direction of understanding bio-macromolecular (i.e. protein-protein, protein-DNA/RNA) interactions and how small molecules could be utilized as useful chemical probes in systematic dissection of these interactions. By no means will this be a trivial undertaking! The development of biological assays towards understanding biomacromolecular interactions is equally challenging as the need for having access to useful small molecule chemical probes.
Synthesis of molecules in a combinatorial fashion can quickly lead to large numbers of molecules. For example, a molecule with three points of diversity (R1, R2, and R3) can generate NR1*NR2*NR3 possible structures, where NR1 ,NR2 , and NR3 are the number of different substituents utilized.
Although combinatorial chemistry has only really been taken up by industry since the 1990s, its roots can be seen as far back as the 1960s when a researcher at Rockefeller University, Bruce Merrifield, started investigating the solid-phase synthesis of peptides. Professor Pieczenik, a colleague of Nobel Laureate Merrifield synthesized the first combinatorial library. In the 1980s researcher H. Mario Geysen developed this technique further, creating arrays of different peptides on separate supports but not a combinatorial library based on random synthesis.
In its modern form, combinatorial chemistry has probably had its biggest impact in the pharmaceutical industry. Researchers attempting to optimize the activity profile of a compound create a 'library' of many different but related compounds. Advances in robotics have led to an industrial approach to combinatorial synthesis, enabling companies to routinely produce over 100,000 new and unique compounds per year.
In order to handle the vast number of structural possibilities, researchers often create a 'virtual library', a computational enumeration of all possible structures of a given pharmacophore with all available reactants. Such a library can consist of thousands to millions of 'virtual' compounds. The researcher will select a subset of the 'virtual library' for actual synthesis, based upon various calculations and criteria.
Combinatorial chemistry is one of the important new methodologies developed by researchers in the pharmaceutical industry to reduce the time and costs associated with producing effective and competitive new drugs.
By accelerating the process of chemical synthesis, this method is having a profound effect on all branches of chemistry, but especially on drug discovery. Through the rapidly evolving technology of combi-chemistry, it is now possible to produce compound libraries to screen for novel bioactivities. This powerful new technology has begun to help pharmaceutical companies to find new drug candidates quickly, save significant money in preclinical development costs and ultimately change their fundamental approach to drug discovery.
Development of Combinatorial Chemistry
---------------------------------------------------------------------------
From a historical perspective, the research efforts made in classical combinatorial chemistry can be briefly outlined in three phases:
In the early 1990s, the initial efforts in the combinatorial chemistry arena were driven by the improvements made in high-throughput screening (HTS) technologies. This led to a demand for access to a large set of compounds for biological screening.
To keep up with this growing demand, chemists were under constant pressure to produce compounds in vast numbers for screening purposes. For practical reasons, the molecules in the first phase were simple peptides (or peptide-like) and lacked the structural complexity commonly found in modern organic synthesis literature.
The second phase started in the late 1990s, when chemists became aware that it is not just about numbers; but something was missing in compounds produced in a combinatorial fashion. Emphasis was thus shifted towards quality rather than quantity.
Like the first phase, the third phase had its origin in progress made by the biomedical community. As the scientific community moved into the post-genomic chemical biology age, there was a growing demand in understanding the role of newly discovered proteins and their interactions with other bio-macromolecules (i.e. other proteins and DNA or RNA). For example, the early goals of the biomedical research community were centered on the identification of small-molecule ligands for biological targets, such as G-protein-coupled receptors (GPCRs) and enzymes.
However, the current challenges are moving in the direction of understanding bio-macromolecular (i.e. protein-protein, protein-DNA/RNA) interactions and how small molecules could be utilized as useful chemical probes in systematic dissection of these interactions. By no means will this be a trivial undertaking! The development of biological assays towards understanding biomacromolecular interactions is equally challenging as the need for having access to useful small molecule chemical probes.
Friday, September 4, 2009
Supramolecular Chemistry.
What is supramolecular chemistry?
It has been described as ‘chemistry beyond the molecule’, whereby a ‘supermolecule’ is a
species that is held together by non-covalent interactions between two or more
covalent molecules or ions. It can also be described as ‘lego™ chemistry’ in which
each lego™ brick represents a molecular building block and these blocks are held
together by intermolecular interactions (bonds), of a reversible nature, to form
a supramolecular aggregate. These intermolecular bonds include electrostatic
interactions, hydrogen bonding, – interactions, dispersion interactions and
hydrophobic or solvophobic effects.
Supramolecular Chemistry: The study of systems involving aggregates of molecules
or ions held together by non-covalent interactions, such as electrostatic interactions,
hydrogen bonding, dispersion interactions and solvophobic effects.
Supramolecular chemistry is a multidisciplinary field which impinges on
various other disciplines, such as the traditional areas of organic and inorganic
chemistry, needed to synthesise the precursors for a supermolecule, physical
chemistry, to understand the properties of supramolecular systems and computational
modelling to understand complex supramolecular behaviour. A great
deal of biological chemistry involves supramolecular concepts and in addition
a degree of technical knowledge is required in order to apply supramolecular
systems to the real world, such as the development of nanotechnological devices.
Supramolecular chemistry can be split into two broad categories;
and functionalities to accept and bind a second molecule via non-covalent
interactions.
It has been described as ‘chemistry beyond the molecule’, whereby a ‘supermolecule’ is a
species that is held together by non-covalent interactions between two or more
covalent molecules or ions. It can also be described as ‘lego™ chemistry’ in which
each lego™ brick represents a molecular building block and these blocks are held
together by intermolecular interactions (bonds), of a reversible nature, to form
a supramolecular aggregate. These intermolecular bonds include electrostatic
interactions, hydrogen bonding, – interactions, dispersion interactions and
hydrophobic or solvophobic effects.
Supramolecular Chemistry: The study of systems involving aggregates of molecules
or ions held together by non-covalent interactions, such as electrostatic interactions,
hydrogen bonding, dispersion interactions and solvophobic effects.
Supramolecular chemistry is a multidisciplinary field which impinges on
various other disciplines, such as the traditional areas of organic and inorganic
chemistry, needed to synthesise the precursors for a supermolecule, physical
chemistry, to understand the properties of supramolecular systems and computational
modelling to understand complex supramolecular behaviour. A great
deal of biological chemistry involves supramolecular concepts and in addition
a degree of technical knowledge is required in order to apply supramolecular
systems to the real world, such as the development of nanotechnological devices.
Supramolecular chemistry can be split into two broad categories;
- host–guest chemistry
- self-assembly
The host component is defined as an organic molecule or ion whose binding sites converge
in the complex. The guest component is any molecule or ion whose binding sites
diverge in the complex.1 A binding site is a region of the host or guest that is
of the correct size, geometry and chemical nature to interact with the other species.
Host–guest complexes include biological systems, such as enzymes and their substrates, with enzymes being the host and the substrates the guest. In terms of coordination chemistry,
metal–ligand complexes can be thought of as host–guest species, where large
(often macrocyclic) ligands act as hosts for metal cations. If the host possesses a
permanent molecular cavity containing specific guest binding sites, then it will
generally act as a host both in solution and in the solid state and there is a
reasonable likelihood that the solution and solid state structures will be similar
to one another. On the other hand, the class of solid state inclusion compounds
only exhibit host–guest behaviour as crystalline solids since the guest is bound
within a cavity that is formed as a result of a hole in the packing of the host
lattice. Such compounds are generally termed clathrates from the Greek klethra,
meaning ‘bars’.
Where there is no significant difference in size and no species is acting as a host for another, the non-covalent joining of two or more species is termed self-assembly. Strictly, self-assembly is an equilibrium between two or more molecular components to produce an aggregate with a
structure that is dependent only on the information contained within the chemical
building blocks.
Nature itself is full of supramolecular systems, for example, deoxyribonucleic
acid (DNA) is made up from two strands which self-assemble via hydrogen
bonds and aromatic stacking interactions to form the famous double helical
structure.
Host–Guest Chemistry: The study of large ‘host’ molecules that are capable of
enclosing smaller ‘guest’ molecules via non-covalent interactions.
Self-Assembly: The spontaneous and reversible association of two or more
components to form a larger, non-covalently bound aggregate.
and functionalities to accept and bind a second molecule via non-covalent
interactions.
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