Robert Combarieu

Use of mike spectrum or cid/mike spectrum of a quasi-molecular or cationized ion obtained by the MBSA-FAB method in order to characterize a polar compound

Abstract CID/MIKE (or MIKE) spectrum of the quasi-molecular (or cationized) ion obtained by the MBSA-FAB method characterizes a polar compound.

Tof-SIMS Analysis of Polymer Bound Fmoc-protected Peptides

Abstract We report the results obtained in the step by step control of a solid phase peptide synthesis carried out on Sheppard polyamide resin by Time of flight - Secondary Ion Mass Spectrometry.

Step-by-step Control by Time-of-flight Secondary Ion Mass Spectrometry of a Peptide Synthesis Carried Out on Polymer Beads

The use of time-of-flight secondary ion mass spectrometry (Tof-SIMS) for the step-by-step control of a peptide synthesis on a solid support is illustrated. The positive secondary ions, issuing from energetic fragmentation, are characteristic of the terminal groups of the step under investigation. The negative secondary ions result from the cleavage of the benzyl ester link between the polymer support and the first amino acid, and provide direct identification of the growing sequence. Tof-SIMS offers this unique analytical possibility without any preliminary separation of the peptide from its support.

Application of time-of-flight secondary ion mass spectrometry to in situ monitoring of solid-phase peptide synthesis on the MultipinTM system

In the rapidly growing field of combinatorial chemistry, the Multipin approach has been used for rapid and efficient multiple parallel syntheses of organic compounds. This strategy is particularly well adapted for the optimization of reaction conditions prior to chemical library syntheses, for the preparation of a wide range of compounds in relation to a lead structure or for the generation of parallel libraries involving complex multistep chemistries. In all cases, direct in situ monitoring of support-bound products would be highly valuable. In this work, time-of-flight secondary ion mass spectrometry was applied to the analysis of support-bound intermediates. The analytical method was applied to a range of crowns loaded with various dipeptides. The solid support was subjected to primary ion bombardment and characteristic ions indicative of both the peptide chain and the polymeric support were unambiguously identified. Analysis could be performed at any stage of the synthesis, and as the method is effectively non-destructive, the analyzed crowns could be further used to prepare target compounds.

TOF-SIMS characterization of the surface of monophase hybrid organic inorganic materials

TOF-SIMS (time of flight secondary ion mass spectrometry) has been used to analyse the surface composition of monophasic hybrid organic-inorganic materials (MHOIM). Gels of type RSiO1.5 obtained from monosilylated precursors RSi(OR)3, (with R=Me, Et and R=hydrogen, alkyl, halogenoalkyl, alkenyl, aromatic and ferrocenyl units) have been analysed and in each case, characteristic mass fragment ions of R groups have been detected and clearly identified owing to the high mass resolution of TOF-SIMS. The large variety of precursors used allows one to conclude that the monosilylated precursors lead, as expected, to solids in which the organic moiety is located at the surface. Thus TOF-SIMS appears to be an efficient tool for the detection of groups located at the surface of amorphous hybrid systems.

MONITORING AND QUANTIFICATION ON SOLID SUPPORT OF A BY-PRODUCT FORMATION DURING PEPTIDE SYNTHESIS BY TOF-SIMS

Abstract To evaluate the amount of pyroglutamic acid formation during the synthesis of glutamic acid containing peptides, resin beads were substituted by known amounts of Fmoc-Glu(O′Bu)-Phe-Ala-NH2 and the corresponding side-product Pyr-Phe-Ala-NH2 and directly analyzed by time of flight-secondary ion mass spectrometry. Detection and quantification of pyroglutamic acid was achieved without release of the peptide chains in solution.

Time-of-flight secondary ion mass spectrometry of Fmoc-amino acids linked to solid supports through ionic interactions

The TOF-SIMS (time-of-flight- secondary ion mass spectrometry) spectra of Fmoc-amino acids linked to solid supports through ionic interactions have been studied to examine if easy desorption of preformed ions from the surface occurred. Preliminary results indicated that the structure of the polymer affected the nature of the recovered ions. However, in the case of widely used polystyrene based supports, characteristic ions of the amino acids were clearly observed with noticeable abundances. Moreover, an analytical criterion to differentiate Fmoc-amino acids linked to various solid supports through either covalent or ionic bonds was established.

Imaging time-of-flight secondary ion mass spectrometry of solid-phase peptide syntheses.

Imaging time-of-flight secondary ion mass spectrometry (TOF-SIMS) of solid-phase peptide syntheses carried out by the Merrifield and Sheppard strategies is described. Mixtures of resin beads mixed at random from batch syntheses or obtained in combinatorial chemistry by the mix and split technique, where each bead is functionalized by a unique peptide, were analyzed directly without any chemical cleavage of the growing chains to assess the nature of the growing structure on any bead of the mixture without its isolation.

Static secondary ion mass spectrometry to monitor solid-phase peptide synthesis

Insights into the direct monitoring of supported peptide synthesis were realized through the design of time of flight static secondary ion mass spectrometry (TOF-S-SIMS) experiments. The mass spectrometric method was carried out at the resin bead level and was found reproducible (intra- and inter-day assays), sensitive (femtomol level) and non-destructive (only 0.01% of the peptides were destroyed by the primary ion beam bombardment). The nature of the peptide—resin linkage governed the recovery of ions characterizing the whole peptide sequence. A S-SIMS cleavable bond was thus required solely in that position to achieve the release of the growing structures from the insoluble support into the gas phase without any fragmentation. Results are presented with standard solid-phase resins allowing linkage through an amide or an ester bond. The latter was orthogonally broken upon the bombardment and thus constituted a convenient S-SIMS cleavable bond.

Comparison of Aluminum Cold Strip Rolling Lubricant Additives

Strip rolling processes are conducted in the mixed lubrication regime, so that boundary additives are an essential feature of the rolling oil. Fatty alcohols are by far the preferred additives: why are they dominant, and what makes them so good for this particular application? A series of model lubricants have been formulated and tested first with the Plane-Strain Compression Test (PSCT) from RT to 200°C. Then some of the formulations have been studied on a high-speed experimental rolling mill. Conclusions from PSCT and rolling tests converge on several points. Fatty alcohols indeed outperform all other formulations; combining them with other molecules may degrade their action.Copyright