User:Mcannos/sandbox/electrospray ionization mass spectrometry of organometallic complexes

Introduction
Electrospray Ionization Mass Spectrometry (ESI-MS) of Organometallic Complexes is a mass spectrometric driven methodology applied to the study of chemical compounds containing metal to carbon bonds. ESI-MS provides rapid, sensitive and simple analysis of commonly air-sensitive and complex organometallic complexes and as such has become increasingly popular to the organometallic chemist. Organometallic chemistry is the study of metal to carbon bond containing complexes which originated with the discovery of main group organometallics such as organolithium, organomagnesium and organozinc compounds. More industrially viable examples of organometallics are the transition metal containing organometallic complexes which are often used in catalytic processes. In addition to catalysis, organometallic compounds are frequently used in the synthesis of new chemical compounds and as a result the study of these compounds has become increasingly important. Several physical methods are available in the study of organometallic complexes such as IR spectroscopy, X-ray Crystallography, and NMR. Additionally, mass spectrometry has been recognized as a useful analytical technique in the analysis of organometallic complexes. Electrospray ionization mass spectrometry has grown in popularity in recent years as an ionization mechanism because of its exploratory capacities.

History
Electrospray was developed my Malcolm Dole, et al., in the late 1960s as a method to nebulize a solution through the generation of highly charged micro-droplets. Electrospray as a process has found many application such as electrostatic painting, electrospinning of polymers, drug delivery, satellite propulsion, and as an ionization technique for mass spectrometry. The technique was refined for mass spectrometry in 1988 by John Fenn who won the Nobel Prize for his work in this area in 2002. Because of its affinity for the analysis of large, polar molecules (proteins and other biomolecules, for example), Electrospray Ionization Mass Spectrometry is exceptionally has become popular and noteworthy over the last few years. The annual number of publications involving ESI-MS has grown from about 100 publications in 1991 to 1900 publications in 2003.

Ionization Mechanism
Mass spectrometry analyzes ions and therefore requires a mechanism by which analyte ions reach the instrument. Electrospray ionization is an ionization technique used to transfer ions from the solution phase to the gas phase such that they may be analysed using mass spectrometry. This is done through pneumatically forcing a solution through a highly charged capillary (held at 2-5kV) which produces a fine spray of droplets. The droplets are desolvated through a process known as a ‘Coulomb explosion’ and further desolvation by pneumatic and thermal means results in the generation of gas phase analyte ions. These ions are accepted into the inlet of the mass spectrometer for analysis. (see also the main article on mass spectrometry).

Experimental Considerations
There are several operating parameters important in obtaining high-quality ESI mass spectra of organometallic complexes, such as :
 * Solvent. Should polar if polar compounds are being analyzed (ex: Dichloromethane, acetonitrile).  Must also be at least moderately volatile for the desolvation process to be efficient.  Volatility also affects the degree to which solvated contaminants appear in the mass spectrum.  Very dilute (< 1 ppb concentration) solutions are required.
 * Ionisation Agents. Ionisation agents may be added to the solution during preparation to promote the formation of ions, depending on what is being analyzed.  Neutral species are typically protonated or cationated.  For example, a small quantity of sodium chloride solution may be added during sample preparation to promote formation of sodiated (M+Na)+ ions.

Advantages of ESI-MS

 * High dynamic range (multiply charging species allows analysis of very high molecular weight compounds)
 * High quality analysis of polar species
 * Exceptional detection limits
 * Soft-ionization, therefore low fragmentation (which may be controlled by cone voltage)
 * Excellent technique for the analysis of air-sensitive samples (see "Recent Developments" below)

Disadvantages of ESI-MS

 * Sensitive to contamination (alkali metals, for example), capillary blockage
 * Not useful if the analyte is uncharged, non-basic, or non-polar

Application to Analysis of Main Group Organometallics
Main group organometallic complexes subtend organosilicon, -tin, -lead, -phosphorous, -arsenic, -mercury and other species and are primarily alkylated or arylated compounds. Electrospray-ionization MS analysis of these compounds varies between each metal class, since the chemical behaviour is different. Main group organometallic halides typically yield the dehalogenated solvolysis product. Observation of the reduced derivatives of these products is sometimes possible through increasing the cone voltage. For example:


 * Me3Pb+ → MePb+ → Pb+

Application to Analysis of Transition Metal Organometallics


Organometallic complexes of transition metals are highly diverse and include metal alkyls, aryls, hydrides, carbonyls, phosphines, and complexes containing π-bound ligands. Singly-charged metal species give strong parent ions in the ESI mass spectrum, similar to other inorganic complexes.

Neutral Metal Carbonyl Compounds
Metal carbonyl compounds of the type Mx(CO)y are very common in inorganic chemistry as synthetic starting materials. They are also important compounds of interest as they are frequently involved as catalytic precursors. For this reason, the study of these compounds through ESI-MS is particularly important. While the study of ionic metal carbonyl compounds by ESI-MS is relatively simple, neutral metal carbonyls can be more challenging.

While neutral metal carbonyl compounds that contain an additional ligand that is available for protonation are easy to deal with, some neutral metal carbonyl compounds and clusters may need to be derivatized in order to ionize the compound. In these cases, the addition of methoxide and azide may be helpful. As an example, addition of a small amount of sodium alkoxide solution promotes nucleophilic attack of a coordinated carbonyl ligand, resulting in a negative addition product. This technique is useful for a wide variety of homoleptic metal carbonyl complexes such as [Cr(CO)6], [W(CO)6], and [Mo(CO)6]. At raised cone voltages, carbonyl compounds tend to experience loss of CO.

Transition Metal Compounds containing π-Bound Ligands
Some popular organometallic ligands which associate with the metal centre through π-bonds are cyclopentadienyl, allyl, and aryl groups. These compounds are effectively undetectable through ESI-MS if they do not contain any ionisable sites and therefore effectively act as spectator ligands. For example, the cyclopentadienyl (Cp) ligand is not easily protonated which means metallocene type complexes, for example, must be ionized though other methods. With ferrocene, for example, the capillary in ESI-MS acts as an electrochemical cell, allowing a one-electron redox process forming [Cp2Fe]+ cations which are detectable by MS.

Pressurized Sample Infusion (PSI)
Study of reactions involving organometallic is of great importance due to the use of such compounds in catalysis. A syringe pump is frequently used for ESI-MS of a solution in order to introduce the solution into the MS at a controlled flow rate. While this method is convenient, it is limited to room temperature reactions. A new technique called Pressurized Sample Infusion (PSI) allows a solution or reaction mixture to be introduced into the MS without the use of a syringe pump at a temperature controlled by an oil bath, or hot plate. PSI is achieved through pressurizing a flask (typically a Schlenk flask) containing the solution using a regulated inert gas. The flask is connected to the inlet of the ESI source by a length of PEEK tubing, which may be fitted with a T-joint connected to a syringe containing the solvent of choice if extra dilution is required. This simple setup facilitates the continuous online monitoring of organometallic catalytic reactions which allows the mechanism and intermediates of such reactions to be probed. Furthermore, the flask may be sealed which allows the safe analysis of air-sensitive organometallics

Analysis of Air Sensitive Compounds
Because many organometallic compounds are highly air-sensitive, it is often inconvenient to remove them from an inert-atmosphere glovebox. One method that has been employed to safeguard samples from decomposition is to prepare them for analysis within the glovebox and inject the sample without removing it from the inert-atmosphere. This eliminates the threat of air and moisture exposure. This solution involves placing a mechanical syringe-pump within the glovebox and installing a line of tubing through a feedthrough leading to the ESI-MS inlet.