Polar acetalization and transacetalization in the gas phase: the Eberlin reaction.
Explore the source record for details and available documents.
Journal Article↗
Biomedical subjects
R G Cooks
Publications and source records attributed to R G Cooks.
Kinetic method for the simultaneous chiral analysis of different amino acids in mixtures.
The kinetic method has been extended to enantiomeric excess (ee) determinations on amino acids present in mixtures. Singly charged trimeric clusters [Cu(II)(ref*)(2)(A(m)) - H](+) are readily generated by electrospraying solutions containing Cu(II), a chiral reference ligand (ref*), and the amino acids (analytes A(m), m = 1-3). A trimeric cluster ion for each amino acid is individually mass-selected and then collisionally activated to cause dissociation by competitive loss of either the reference ligand or the analyte. For each analyte in the mixture, as shown from separate experiments, the logarithm of the ratio of the fragment abundances for the complex containing one enantiomer of this analyte expressed relative to that for the fragments of the corresponding complex containing the other enantiomer is linearly related to the enantiomeric composition of the amino acid. Formation and dissociation of each trimeric complex ion are shown to occur independently of the presence of other analytes. Chiral selectivity appears to be an intrinsic property and the chiral selectivity R(chiral(m)) measured from the mixture of analytes is equal to R(chiral) measured for the pure analyte. The sensitive nature of the methodology and the linear relationship between the logarithm of the fragment ion abundance ratio and the optical purity, characteristic of the kinetic method, allow the determination of chiral impurities of less than 2% ee in individual compounds present in mixtures by simply recording the ratios of fragment ion abundances in a tandem mass spectrum.
Amino Acids↗
Quantitative chiral analysis of sugars by electrospray ionization tandem mass spectrometry using modified amino acids as chiral reference compounds.
Rapid quantitative enantiomeric analysis of mannose, glucose, galactose, and ribose is achieved using electrospray ionization and cluster ion dissociation with data analysis by the kinetic method. Several modified amino acids (N-Ac-L-Phe, N-benzoyl-L-Phe, N-t-Boc-L-Phe, N-Ac-L-Pro, N-t-Boc-L-Pro, N-Fmoc-L-Pro, N-Ac-L-Tyr, O-Me-L-Tyr) and four transition divalent metal cations (Co2+, Cu2+, Ni2+, and Zn2+) were tested to select the best system for chiral recognition and quantitation of each sugar. Quantitative determinations of the enantiomeric compositions of sugar solutions were achieved using either multiple- or two-point calibration curves; differences between the actual and experimental values were <2% enantiomeric excess (ee).
Amino Acids↗
Ligand and metal-ion effects in metal-ion clusters used for chiral analysis of alpha-hydroxy acids by the kinetic method.
Chiral recognition of alpha-hydroxy acids has been achieved, and mixtures of enantiomers have been quantified in the gas phase, by using the kinetics of competitive unimolecular dissociation of singly-charged transition metal ion-bound trimeric complexes, [M(II)(A)(ref*)(2)-H](+) (M(II)=divalent transition metal ion; A=alpha-hydroxy acid; ref*=chiral reference ligand), to form the dimeric complexes [M(II)(A)(ref*)-H](+) and [M(II)(ref*)(2)-H](+). Chiral selectivity, the ratio of these two fragment ion abundances for the complex containing the analyte in one enantiomeric form expressed relative to that for the fragments of the corresponding complex containing the other enantiomer, ranges from 0.65 to 7.32. Chiral differentiation is highly dependent on the choice of chiral reference compound and central metal ion. The different coordination geometry of complexes resulting from the different d-orbital electronic configurations of these transition metal ions plays a role in chiral discrimination. Of all the transition metal ions examined chiral recognition is lowest for Cu(II), because of large distortion of the coordination complexes, and hence weak metal-ligand interactions and small stereochemical effects. It seems that two independent pi-cation interactions occur when N-acetyl-substituted aromatic amino acids used as the reference ligands and this accounts for improved chiral discrimination. If both metal-ligand and ligand-ligand interactions are optimized, large chiral selectivity is achieved. The sensitive nature of the methodology and the linear relationship between the logarithm of the fragment ion abundance ratio and the optical purity, which are intrinsic to the kinetic method, enable mixtures to be analyzed for small enantiomeric excess ( ee) by simply recording the ratios of fragment ion abundances in a tandem mass spectrum.
Calibration↗
Direct analysis of semivolatile organic compounds in air by atmospheric pressure chemical ionization mass spectrometry.
Atmospheric pressure chemical ionization is employed for direct air analysis, without ion source modification, by using the sheath gas as the sample transport agent. A simple modification of the sheath gas inlet line allows introduction of gaseous samples into a commercial atmospheric pressure chemical ionization source. Optimization and testing of this novel air sampling method are described and detection of semivolatile compounds is shown. The analytical performance of the technique is established with methyl salicylate, including a limit of quantification of 100 pptr, a limit of detection of 50 pptr, a linear response from 100 pptr to 20 ppb, and rise and fall times of 12 and 20 s, respectively. Using reagent ion monitoring, it is shown that the protonated methanol dimer is the principal CI reagent ion leading to protonated dimethyl methylphosphonate, while the monomer is mainly responsible for protonating methyl salicylate. Since the formation of the CI reagent (methanol clusters) can be controlled by simple variation of experimental parameters, the selectivity of the method can be easily adjusted to suit the targeted analyte. Performance is found to be independent of the choice of air or nitrogen as the sheath gas (and thus as the sample matrix) and this, together with the sensitivity and speed of the technique, make it promising for field studies.
Journal Article↗
Rapid enantiomeric quantification of an antiviral nucleoside agent (D,L-FMAU, 2'-fluoro-5-methyl-beta,D,L-arabinofurano-syluracil) by mass spectrometry.
A novel mass spectrometric method is applied to rapid, accurate (<1%) quantification of chiral Clevudine (L-FMAU, 2'-fluoro-5-methyl-beta,L-arabinofuranosyluracil), a potent antiviral nucleoside agent against hepatitis B virus. Transition metal bound complex ions containing the chiral drug are generated by electrospray ionization mass spectrometry and subjected to collision-induced dissociation. The ratio of the two competitive dissociation rates is related to the enantiomeric composition of the drug mixture, allowing the determination of enantiomeric contamination in the drug.
Antiviral Agents↗
Serine octamer metaclusters: formation, structure elucidation and implications for homochiral polymerization.
Multiply charged serine metaclusters (composed of two or more homochiral octameric units) are generated by electrospray ionization, and their unique fused structures (hydrogen-bonded through the sticky ends of the drum-shaped octameric units) have been elucidated using tandem mass spectrometry experiments and molecular mechanics calculations.
Hydrogen Bonding↗
Organic chloramine analysis and free chlorine quantification by electrospray and atmospheric pressure chemical ionization tandem mass spectrometry.
Atmospheric pressure chemical ionization (APCI) and electrospray ionization (ESI), together with tandem mass spectrometry (MSn), are used to study the mechanism of chlorination of amines and to develop a method for qualitative and quantitative determination of organic chloramines. Cyclohexylamine and 1,4-butanediamine (putrescine) are used as model compounds to investigate the mechanisms of the reactions between primary aliphatic amines and hypochlorous acid (aqueous Cl2). The chlorination products are identified and characterized by collision-induced dissociation (CID) and H/D exchange. Chlorination occurs by electrophilic addition of Cl+ and may be followed by HCl elimination, hydrolysis, or, in the case of diamines, amine elimination by intramolecular nucleophilic substitution. The relative rates of chlorination at amine and chloramine nitrogens are a function of pH and depend on the basicity of the amine. A novel method for active chlorine quantification using ESI or APCI mass spectrometry is suggested on the basis of the extent of chlorination of a sacrifical amine standard. This measurement has a limit of detection for N-chlorocyclohexylamine in the range of 0.1-10 microM, a linear dynamic range of 10(2)-10(3), and an accuracy of +/-10%, as determined for wastewater samples.
Journal Article↗
Chiroselective self-directed octamerization of serine: implications for homochirogenesis.
Serine undergoes chiroselective self-directed oligomerization to form a singly protonated octamer under positive ion electrospray conditions, as identified by ion trap tandem mass spectrometry. The experiments also show a series of higher-order clusters (metaclusters) corresponding to [(Ser8H)n]n+, n = 1, 2, 3. There is a magic number effect favoring formation of the protonated octamer over its homologues and also a strong preference for octamer formation from homochiral serine molecules. Collision-induced dissociation suggests that the protonated octamer is composed of four hydrogen-bonded dimers, stabilized by further extensive hydrogen bonding. Density functional calculations support this model and show that the protonated homochiral octamer is energetically stabilized relative to its possible fragments (dimer plus protonated hexamer, etc). The calculations also show that heterochiral octamers are less stable than homochiral octamers (e.g., the protonated 7:1 cluster is 2.1 kcal/mol less stable than the 8:0 analogue). The implications of these results for the origin of homochirality are discussed.
Evolution, Chemical↗
Mass spectrometric quantitation of chiral drugs by the kinetic method.
A novel mass spectrometric method for rapid, accurate (2-4% ee) quantitation of chiral drugs is described. Copper(II)-bound complexes of seven model drugs (atenolol, DOPA, ephedrine, pseudoephedrine, isoproterenol, norepinephrine, propranolol) with chiral reference compounds (L-amino acids) are generated by electrospray ionization mass spectrometry. The trimeric complex ions (three chiral ligands--one of the analyte and two of the reference compound) are collisionally activated, and they undergo dissociation by competitive loss of either the neutral reference or the neutral drug molecule. The ratio of the two competitive dissociation rates, viz. the product ion branching ratio, is related via the kinetic method to the enantiomeric composition of the drug mixture. A two-point calibration curve, derived from the kinetic method, allows rapid quantitation of enantiomeric excess of drug mixtures. The chiral sensitivity of the method is such as to allow determination of mixtures with a few percent enantiomeric contamination.
Dihydroxyphenylalanine↗
International Mass Spectrometry Society (IMSS).
This paper gives a brief description of the recently formalized International Mass Spectrometry Society (IMSS). It is presented here in order to increase awareness of the opportunities for collaboration in mass spectrometry in an international context. It also describes the recent 15th International Mass Spectrometry Conference, held August/September 2000, in Barcelona. Each of the authors is associated with the IMSS. The 15th Conference, which covers all of mass spectrometry on a triennial basis, was chaired by Professor Emilio Gelpi of the Instituto de Investigaciones Biomedicas, Barcelona. The outgoing and founding President of the IMSS is Professor Graham Cooks, Purdue University, and the incoming President is Professor Nico Nibbering, University of Amsterdam. Similar material has been provided to the Editors of other journals that cover mass spectrometry.
International Cooperation↗
Reactions of BBr(n)(+) (n = 0--2) at fluorinated and hydrocarbon self-assembled monolayer surfaces: observations of chemical selectivity in ion--surface scattering.
Ion-surface reactions involving BBr(n)(+) (n = 0--2) with a fluorinated self-assembled monolayer (F-SAM) surface were investigated using a multi-sector scattering mass spectrometer. Collisions of the B(+) ion yield BF(2)(+) at threshold energy with the simpler product ion BF(+)* appearing at higher collision energies and remaining of lower abundance than BF(2)(+) at all energies examined. In addition, the reactively sputtered ion CF(+) accompanies the formation of BF(2)(+) at low collision energies. These results stand in contrast with previous data on the ion-surface reactions of atomic ions with the F-SAM surface in that the threshold and most abundant reaction products in those cases involved the abstraction of a single fluorine atom. Gas-phase enthalpy data are consistent with BF(2)(+) being the thermodynamically favored product. The fact that the abundance of BF(2)(+) is relatively low and relatively insensitive to changes in collision energy suggests that this reaction proceeds through an entropically demanding intermediate at the vacuum--surface interface, one which involves interaction of the B(+) ion simultaneously with two fluorine atoms. By contrast with the reaction of B(+), the odd-electron species BBr(+)* reacts with the F-SAM surface to yield an abundant single-fluorine abstraction product, BBrF(+). Corresponding gas-phase ion--molecule experiments involving B(+) and BBr(+)* with C(6)F(14) also yield the products BF(+)* and BF(2)(+), but only in extremely low abundances and with no preference for double fluorine abstraction. Ion--surface reactions were also investigated for BBr(n)(+) (n = 0-2) with a hydrocarbon self-assembled monolayer (H-SAM) surface. Reaction of the B(+) ion and dissociative reactions of BBr(+)* result in the formation of BH(2)(+), while the thermodynamically less favorable product BH(+)* is not observed. Collisions of BBr(2)(+) with the H-SAM surface yield the dissociative ion-surface reaction products, BBrH(+) and BBrCH(3)(+). Substitution of bromine atoms on the projectile by hydrogen or alkyl radicals suggests that Br atoms may be transferred to the surface in a Br-for-H or Br-for-CH(3) transfer reaction in an analogous fashion to known transhalogenation reactions at the F-SAM surface. The results for the H-SAM surface stand in contrast to those for the F-SAM surface in that enhanced neutralization of the primary ions gives secondary ion signals one to two orders of magnitude smaller than those obtained when using the F-SAM surface, consistent with the relative ionization energies of the two materials.
Journal Article↗
Metal-assisted esterification: glutaric acid-iron(II) complexes in the gas phase.
Transition metal ions are routinely used to assist organic reactions; however, direct detection of the intermediates in such reactions is uncommon. Here, we demonstrate a transition metal ion-assisted reaction between glutaric acid (L) and methanol, using electrospray ionization mass spectrometry (ESI-MS). Esterification of glutaric acid does not occur in aqueous methanol solution under ESI conditions, but the FeII-bound acid cluster, [FeII L2 - H]+, adds methanol and dehydrates to give rise to an abundant product ion with a 14 Da increased mass. The occurrence of methyl esterification is supported by collision-induced dissociation and isotopic labeling data, which indicate that the sequence by which the product ion is generated is loss of water, followed by the addition of methanol. Electrospray ionization conditions, specifically the tube lens offset voltage, strongly affect the reaction efficiency, presumably through control of the dehydration process. Other transition metal ions, such as NiII, ZnII, CoII and CuII, also show distinctive metal-assisted reactions.
Cobalt↗
External interface for trap-and-release membrane introduction mass spectrometry applied to the detection of inorganic chloramines and chlorobenzenes in water.
Construction and evaluation of an external configuration trap-and-release membrane introduction system for mass spectrometry is described. This novel interface allows independent control of the temperature of the membrane and eliminates the dependence of membrane heating efficiency on its position in the ion source. The external trap-and-release MIMS configuration is successfully applied to detection of inorganic chloramines and chlorobenzenes. The method is shown to give temporal resolution of volatile vs. semi-volatile compounds, which increases its sensitivity for semi-volatiles in the presence of volatiles and provides an additional selectivity parameter. Further selectivity is provided by tandem mass spectrometry.
Chloramines↗
Differentiation and quantitation of isomeric dipeptides by low-energy dissociation of copper(II)-bound complexes.
Application of the kinetic method based on the dissociation of transition metal centered cluster ions is extended from chiral analysis (Tao, W. A.; Zhang, D.; Nikolaev, E. N.; Cooks, R. G. J. Am. Chem. Soc. 2000, 122, 10598) to quantitative analysis of isomeric mixtures, including those with Leu/Ile substitutions. Copper(II)-bound complexes of pairs of peptide isomers are generated by electrospray ionization mass spectrometry and the trimeric complex [CuII(ref)2(A) - H]+ (analyte A, a mixture of isomeric peptides; reference compound ref, usually a peptide) is caused to undergo collisional dissociation. Competitive loss of the neutral reference compound or the neutral analyte yields two ionic products and the ratio of rates of the two competitive dissociations, viz. the product ion branching ratio R is shown to depend strongly on the regiochemistry of the analyte in the precursor [CuII(A)(ref)2 - H]+ complex ion. Calibration curves are constructed by relating the branching ratio measured by the kinetic method, to the isomeric composition of the mixture to allow rapid quantitative isomer analysis.
Amino Acids↗
Gas-phase SN2 reactivity of dicoordinated borinium cations using pentaquadrupole mass spectrometry.
We report gas phase ion/molecule reactions between dialkoxyborinium cations (RO-B+-OR) and small organic amides, such as N,N-dimethylformamide and N,N-diethylpropionamide. Besides direct addition at boron, the results show efficient SN2 methyl transfer from the borinium ion to the amide. Isotopic labeling and collision-induced dissociation (CID) of the methyl transfer products demonstrate O-methylation of the amide. Methyl substitution at the alpha-carbon of the amide affects the degree of alkylation and adduct formation. Direct proton abstraction via beta-elimination is a major competitive reaction for substituents other than methyl. Ab initio calculations at the B3LYP/6-31G(d) level indicate that SN2 transmethylation is highly exothermic with O-methylation favored over N-methylation by 14.8 kcal/mol.
Journal Article↗
Single-sided membrane introduction mass spectrometry for on-line determination of semi-volatile organic compounds in air.
Construction, optimization, and testing of a novel single-sided configuration for a semi-permeable [poly(dimethylsiloxane); PDMS] membrane introduction system for mass spectrometry is described. On-line detection of semi-volatile organic compounds of environmental interest is shown, including lindane (a pesticide), hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) (an explosive), butylated hydroxytoluene (BHT) (an antioxidant), 1,2-dichlorobenzene, dimethylmethyl phosphonate (DMMP) (a chemical warfare agent simulant) and naphthalene. The technique has limits of detection in the sub-ppb range. with rise times of 4 to 7 s and fall times of 12 to 36 s and a response that is linear over 4 orders of magnitude (from 0.1 ppb to 1000 ppb for DMMP). The cycle time, from crude air sampling to acquisition of results, is approximately 1 min. No sample preparation is necessary.
Journal Article↗
Surface modification using a commercial triple quadrupole mass spectrometer.
We report instrumental modifications to a commercial mass spectrometer that allow surface modification experiments to be performed using low-energy (electronvolt range) mass-selected ion beams. The design of the detector housing allows placement of the surface on the ion optical axis and some distance beyond the off-axis detector. Manipulation of the potentials applied to the final lens, detector housing, conversion dynode, and electron multiplier allow the ions to pass through the detector housing and impinge upon the surface without loss of the normal mode of detector operation. Ex situ analysis of the modified surface is performed using a home-built multisector mass spectrometer. The ability to modify organic thin films is demonstrated by a number of soft landing and surface modification experiments including (i) soft landing of (CH3)2SiNCS+ ions formed from trimethylsilyl isothiocyanate upon a fluorinated self-assembled monolayer (F-SAM) surface, (ii) soft landing and dissociative soft landing of the pseudomolecular cation of triphenylpyrylium tetrafluoroborate, viz. the triphenylpyrylium cation, upon an F-SAM surface, (iii) dissociative soft landing of 35ClCH2(CH3)2SiOSi(CH3)2+ formed from 1,3-bis(chloromethyl)disiloxane upon an F-SAM surface, (iv) surface passivation by reaction of the trimethylsilyl cation, Si(CH3)3+, with a hydroxyl-terminated self-assembled monolayer (OH-SAM), and (v) transhalogenation by reaction of CCl3+ (m/z 119) with an F-SAM surface.
Journal Article↗