Organic ions in the gas phase—XXI: Synthesis and mass spectra of deuteriothiophenes

Mass-spectral and n.m.r. analysis of thiophenes labeled by exchange with deuteriosulfuric acid establishes that exchange at the 2 and 5 positions is essentially complete before any deuterium is incorporated at positions 3 and 4. Thus, such exchange is a satisfactory procedure for position-specific labeling. Mass spectra of the labeled thiophenes show that about 60% of the [CHS]⁺ ion yield is derived from molecular ions that have not undergone prior rearrangement. The remaining 40% arises by a path or paths in which the four hydrogen atoms lose position identity. Other decomposition paths contributing to the mass spectrum are characterized by more nearly complete scrambling of hydrogens.     

Stereoisomeric effects on mass spectra—I. A Review

The unimolecular reactions that give rise to mass spectra are controlled by spatial relationships and energy considerations. In molecules that contain a heteroatom, elimination reactions, involving bond-making as well as breaking, are often prominent, e.g. loss of water from alcohols. The ease of such reactions depends on spatial relationships in the molecule, and the resultant ion intensities in the spectra of geometric isomers can consequently be correlated with differences in geometry and hence furnish a basis for assigning structures. Processes that do not involve bond-making do not have such rigorous geometric requirements, but depend rather on attainment of a transition state defined in terms of a minimum energy content. Common product ions from stereoisomeric hydrocarbons seem often to arise via a common transition state. When this condition holds, the difference between the enthalpies of the isomers is reflected in the relative appearance potentials and–though the cause-and-effect relationship here is less direct and more readily obscured by other factors–relative intensities of the common product derived from the isomers. In both classes of processes, the spectra of stereoisomers can be simplified and made more distinctive by lowering source temperature and ionizing voltage.     

Cationated cyclopropanes as reaction intermediates in mass spectra: an earlier incarnation of ion-neutral complexes

The appearance a decade ago of the concept of ion-neutral complexes as intermediates in unimolecular decompositions constituted a major advance in mechanistic interpretation of mass spectra. The concept, however, was not new; it goes back to the introduction of the cationated cyclopropane in the mid-1950s. Its development did not occur via a smooth progression; rather, its history bridges a sharp discontinuity. The early workers, in a curious historical quirk, failed to generalize on the idea beyond complexes in which the neutral component is cyclopropane or a closely related species. Hence it took an independent rediscovery of the concept to usher in the rapid growth and wide application that characterize its present stage of development.     

Chemical modification of the electrical properties of hydrogenated amorphous carbon films

Semiconducting films of hydrogenated amorphous carbon (a-C:H), prepared via the dc glow discharge decomposition of C₂H₂, have been successfully doped via incorporation of B and P during growth. The doping efficiency achieved was comparable to that achieved in a-Si:H produced in a like manner. For a-C:H films deposited at T_d=250C,

(RT) increased from 10^-12 to 10^-7 ohm^-1 cm^-1 when either 1% PH₃ or 10% B₂H₆ were added to the C₂H₂. A shift of the Fermi level E_F of about 0.7 eV is inferred from changes in the “activation” energy of conduction.     

Tropylium,chlorine isotopic abundances,monomeric metaphosphate anion,and conestoga wagon theory

As I look back over a career in mass spectrometry, three high points stand out especially prominently. These are associated with (1) the tropylium model for the C_uH ₇ ⁺ ion in the mass spectra of toluene and other alkylbenzenes, (2) revision of the previously accepted value for the natural abundance of the chlorine isotopes, and (3) the first direct observation of the monomeric metaphosphate anion, which had been for a quarter of a century an elusive, suspected reaction intermediate. Studies of organic ions in the rarefied atmosphere of the mass spectrometer, where only unimolecular processes are allowed, have deepened my appreciation of the role and ubiquity of bimolecular processes in more conventional chemical contexts. Consideration of the two categories of molecular behavior has prompted me to seek and find, for a selected system in the mass spectrometer, parallels both in condensed-phase chemistry and, by an anthropomorphic extension, in human behavior.     

Therapeutic Targeting of Oncogenic K‐Ras by a Covalent Catalytic Site Inhibitor

We report the synthesis of a GDP analogue, SML‐8‐73‐1, and a prodrug derivative, SML‐10‐70‐1, which are selective, direct‐acting covalent inhibitors of the K‐Ras G12C mutant relative to wild‐type Ras. Biochemical and biophysical measurements suggest that modification of K‐Ras with SML‐8‐73‐1 renders the protein in an inactive state. These first‐in‐class covalent K‐Ras inhibitors demonstrate that irreversible targeting of the K‐Ras guanine‐nucleotide binding site is potentially a viable therapeutic strategy for inhibition of Ras signaling.