Denis Lesage

Formation of noncovalent complexes is one of the approaches to perform chiral analysis with mass spectrometry. Enantiomeric distinction of amino acids (AAs) based on the relative rate constants of competitive fragmentations of quaternary copper complexes is an efficient method for chiral differentiation. Here, we studied the complex [Cu-II,(Phe,PhG,Pro-H)](+) (m/z 493) under resonant collision-induced dissociation conditions while varying the activation time. The precursor ion can yield two main fragments through the loss of the non-natural AA phenylglycine (PhG): the expected product ion [Cu-II,(Phe,Pro-H)](+) (m/z 342) and the reduced product ion [Cu-I,(Phe,Pro)](+) (m/z 343). Enantioselective reduction describes the difference in relative abundance of these ions, which depends on the chirality of the precursor ion: the formation of the reduced ion m/z 343 is favored in homochiral complexes (DDD) compared to heterochiral complexes (such as LDD). Energy-resolved mass spectrometry data show that reduction, which arises from rearrangement, is favored at a low collision energy (CE) and long activation time (ActT), whereas direct cleavage preferentially occurs at a high CE and short ActT. These results were confirmed with kinetic modeling based on RRKM theory. For this modeling, it was necessary to set a pre-exponential factor as a reference, so that the E-0 values obtained are relative values. Interestingly, these simulations showed that the critical energy E-0 required to form the reduced ion is comparable in both homochiral and heterochiral complexes. However, the formation of product ion m/z 342 through direct cleavage is associated with a lower E-0 in heterochiral complexes. Consequently, enantioselectivity would not be caused by enhanced reduction in homochiral complexes but rather by direct cleavage being favored in heterochiral complexes.

Synthesis of host molecules that feature well‐defined characteristics for molecular recognition of guest molecules is often a major aim of synthetic host–guest (H–G) chemistry. A key consideration in evaluating the selectivity of hosts and the affinities of guests is the measurement of binding energies of obtained H–G complexes. In contrast to nuclear magnetic resonance (NMR) or fluorescence measurements that are capable of measuring binding strengths in solution, mass spectrometry offers the opportunity to measure gas‐phase binding energies. Presented in this article is a higher energy collision dissociation (HCD) approach for determining critical energies of dissociation of H–G complexes. Experiments were performed on electrospray ionization (ESI)‐generated H–G pairs in an LTQ‐XL/Orbitrap hybrid instrument. The presented HCD approach requires preliminary calibration of the internal energy distribution of generated ions that was achieved by the use of activation parameters that were known from previous low‐energy collision‐induced dissociation (low‐energy CID) experiments. Internal energy deposition was modeled based on a truncated Maxwell–Boltzmann distribution and characteristic temperature (T_char). Using this method, critical energies of dissociation were determined for 10 H–G biologically relevant complexes of the heteroditopic hemicryptophane cage host (Host). Obtained results are compared with those found previously by low‐energy CID. The use of this HCD technique is relatively straightforward, although its implementation does require knowledge (or a presumption) about the Arrhenius pre‐exponential factor of the complexes to obtain their critical energies of dissociation.

A low‐energy collision induced dissociation (CID) (low‐energy CID) approach that can determine both activation energy and activation entropy has been used to evaluate gas‐phase binding energies of host‐guest (H‐G) complexes of a heteroditopic hemicryptophane cage host (Zn (II)@1) with a series of biologically relevant guests. In order to use this approach, preliminary calibration of the effective temperature of ions undergoing resonance excitation is required. This was accomplished by employing blackbody infrared radiative dissociation (BIRD) which allows direct measurement of activation parameters. Activation energies and pre‐exponential factors were evaluated for more than 10 H‐G complexes via the use of low‐energy CID. The relatively long residence time of the ions inside the linear ion trap (maximum of 60 s) allowed the study of dissociations with rates below 1 s⁻¹. This possibility, along with the large size of the investigated ions, ensures the fulfilment of rapid energy exchange (REX) conditions and, as a consequence, accurate application of the Arrhenius equation. Compared with the BIRD technique, low‐energy CID allows access to higher effective temperatures, thereby permitting one to probe more endothermic decomposition pathways. Based on the measured activation parameters, guests bearing a phosphate (―OPO₃²⁻) functional group were found to bind more strongly with the encapsulating cage than those having a sulfonate (―SO₃⁻) group; however, the latter ones make stronger bonds than those with a carboxylate (―CO₂⁻) group. In addition, it was observed that the presence of trimethylammonium (―N(CH₃)₃⁺) or phenyl groups in the guest's structure improves the strength of H‐G interactions. The use of this technique is very straightforward, and it does not require any instrumental modifications. Thus, it can be applied to other H‐G chemistry studies where comparison of bond dissociation energies is of paramount importance.

Proline proton affinity PA(Pro) was previously measured by extended kinetic methods with several amines as reference bases using a triple quadrupole mass spectrometer ( J Mass Spectrom 2005; 40: 1300). The measured value of 947.5 ± 5 kJ.mol⁻¹ differs by more than 10 kJ.mol⁻¹ from previous reported experimental or calculated values. This difference may be explained in part by the existence of relatively large entropy difference between the two dissociation channels (ΔΔS^‡_avg = 31 ± 10 J.mol⁻¹.K⁻¹) and by the inaccuracy of the amines proton affinity used as reference bases. In the present work, these experimental measurements were reinvestigated by RRKM modeling using MassKinetics software. From this modeling, a new PA value of 944.5 ± 5 kJ.mol⁻¹ and a ΔΔS^‡_avg(600K) value of 33 ± 10 J.mol⁻¹.K⁻¹ are determined. However, the difference between experiment and recent theoretical calculations remains large (10 kJ.mol⁻¹). These RRKM simulations allow also accessing to the effective temperature parameter (T _eff) and to discuss the meaning of this term. As previously reported, T _eff mainly depends on the internal energy and on the decomposition time as well. It also depends on the critical energies and on the transition state. Considering the entrance of the collision cell as a new ion source, T _eff is finally shown to be close to a characteristic temperature (T _char).

Redox labeled DNAs are of increasing interest for the fabrication of next generation molecular tools. In the present work we are investigating the use of various redox labeled dNTPs, ddNTPs and DNA primers for use in detection of diseases. We have reported the use of Polyoxometalate (POM) labeled DNA primers and dNTPs for use in PCR and subsequently used for direct electrochemical detection of PCR products. The use of POM labeled DNAs in PCR enabled us to check the compatibility with polymerases and PCR incorporability of the modified DNAs. Furthermore we have investigated the solid-phase array based primer extension (é-PEX) with redox labelled ddNTPs (ferrocene (Fc), anthraquinone (AQ) phenothiazine (PTZ) and methylene blue (MB)) to prove the strategy of detection of single nucleotide polymorphisms using the labeled ddNTPs. This strategy will allow the development of cost-effective, rapid and user-friendly platform for the screening of known and unknown genetic mutations.

Negatively charge-tagged N-heterocyclic carbenes have been formed in solution via deprotonation of imidazolium ions bearing acid side groups and transferred to the gas phase via ESI(–)-MS. The stru...

The kinetic method is a widely used approach for the determination of thermochemical data such as proton affinities (PA) and gas-phase acidities (ΔH° _acid ). These data are easily obtained from decompositions of noncovalent heterodimers if care is taken in the choice of the method, references used, and experimental conditions. Previously, several papers have focused on theoretical considerations concerning the nature of the references. Few investigations have been devoted to conditions required to validate the quality of the experimental results. In the present work, we are interested in rationalizing the origin of nonlinear effects that can be obtained with the kinetic method. It is shown that such deviations result from intrinsic properties of the systems investigated but can also be enhanced by artifacts resulting from experimental issues. Overall, it is shown that orthogonal distance regression (ODR) analysis of kinetic method data provides the optimum way of acquiring accurate thermodynamic information.

Control of the ion internal energy in mass spectrometry is needed to establish a workable mass spectral library. The purpose of this study is to understand and to compare the pressure effects on the collision‐induced dissociation (CID) spectrum pattern recorded using triple quadrupole instruments. The monoprotonated Leucine enkephalin [YGGFL, H⁺] was used as a thermometer molecule to calibrate the electrospray ionization (ESI) and the CID internal energies deposited on the molecular species and the time scale of ion decompositions. The survival yield and the ratio of a₄/b₄ fragment ions were mainly monitored. The energy uptake for the ESI source geometry used in our study has no impact on the CID spectrum fingerprint. The collision cell pressure for the [YGGFL, H⁺] has a major influence on the SY curves slope and on the experimental time scale. To demonstrate the pressure effect on internal energy distribution, three models (threshold, thermal and collisional) based on RRKM theory were built using the Masskinetics software. As a result, the limit of each model is discussed, and the investigation demonstrates that the thermal model, using truncated Maxwell‐Boltzmann internal energy distribution, is well‐suited for simulating the experimental data at high pressure widely used in the analytical conditions. Copyright © 2013 John Wiley & Sons, Ltd.