Leonard J. Chyall

DETERMINATION OF THE PROTON AFFINITY AND ABSOLUTE HEAT OF FORMATION OF CYCLOPROPENYLIDENE

Abstract The proton affinity and absolute heat of formation of cyclopropenylidene (c-C 3 H 2 ) have been derived from the translational energy threshold for endothermic proton transfer from c-C 3 H 3 + to ammonia in a flowing afterglow triple quadrupole instrument: c-C 3 H 3 + + NH 3 → c-C 3 H 2 + NH 4 + . The cyclopropenium cation C 3 H 3 + was prepared in a helium flow reactor at room temperature by the reaction of ionized ethylene with acetylene, and from dissociative electron ionization of bromocyclopropane. The kinetic energy dependence of the cross-sections for proton transfer from this ion to ammonia and other neutral amines was characterized in a triple quadrupole mass analyzer. The endothermicity for the reaction with ammonia was determined to be 23.3 ± 1.8 kcal mol −1 . Combining this with the known proton affinity (PA) of ammonia (204.0 ± 1.0 kcal mol −1 ) gives a value for PA(c-C 3 H 2 ) of 227.3 ± 2.1 kcal mol −1 . From the measured proton affinity and the known heats of formation of c-C 3 H 3 + and the proton, the 298 K heat of formation of cyclopropenylidene is determined to be 119.5 ± 2.2 kcal mol −1 . This value is slightly higher than a previous experimental estimate, but is in good agreement with the 298 K heat of formation predicted by high level molecular orbital calculations.

Distonic ions of the “ate” class

The gas phase synthesis, structure, and reactivity of distonic negative ions of the “ate” class are described. “Ate”-class negative ions are readily prepared in the gas phase by addition of neutral Lewis acids, such as BF3, BH3, and AlMe3, to molecular anions, carbene negative ions, and radical anions of biradicals. The ions contain either localized σ- or delocalized π-type radical moieties remote from relatively inert borate and aluminate charge sites. The free radical reactivity displayed by these ions appears to be independent of the charge site. As an example, the distonic alkynyl radical (·C≡CBF3−) is highly reactive and undergoes radical coupling reactions with NO2, NO, H2C=CH-CN, and H2C=CH-CH3. Radical-mediated group and atom transfers are observed with O2, CS2, and CH3SSCH3. Furthermore, H-atom abstraction reactions are observed, in accordance with the predicted high C-H bond strength of this species [DH298(H-C2BF3−)=130.8 kcal mol−1]. High level ab initio molecular orbital calculations on the prototype “ate”-class distonic ion · CH2BH3− and its conventional isomer CH3BH2·− reveal that CH3BH2·− is 3.2 kcal/mol more stable than the α-distonic form. However, the calculations also show that CH3BH2·− is unstable with respect to electron detachment, and only the α-distonic form ·CH2BH3− should be experimentally observed in the gas phase.

COMBINING ELECTROSPRAY IONIZATION AND THE FLOWING AFTERGLOW METHOD

The design and implementation of a simple electrospray ionization source for a flowing afterglow/triple quadrupole device are described. Ions can be electrosprayed directly into the room temperature flow tube through a heated capillary without the need for differential pumping or ion focusing. Detected ion currents at the detector sampling orifice as high as 3 pA have been achieved, and the mass spectra indicate little or no re-clustering of the desolvated ions with the background solvent vapor in the flow tube. Spatially and temporally resolved ion/molecule reactions of electrosprayed ions can be carried out in the flow reactor under thermal energy conditions. Sufficient ion densities can be achieved for tandem mass spectrometric experiments in the triple quadrupole analyzer, including energy-resolved collision-induced dissociation. Selected chemical applications illustrating these features are described, including proton transfer reactions with aromatic polysulfonate dianions and multiply protonated polypeptides and threshold CID of a doubly charged transition metal coordination complex.

New solid-state chemistry technologies to bring better drugs to market: knowledge-based decision making

Modern drug development demands constant deployment of more effective technologies to mitigate the high cost of bringing new drugs to market. In addition to cost savings, new technologies can improve all aspects of pharmaceutical development. New technologies developed at SSCI, Inc. include solid form development of an active pharmaceutical ingredients. (APIs) are PatternMatch software and capillary-based crystallisation techniques that not only allow for fast and effective solid form screening, but also extract maximum property information from the routine screening data that is generally available. These new technologies offer knowledge-based decision making during solid form development of APIs and result in more developable API solid forms.