Gas-phase reactivity of five differently substituted positively charged phenyl radicals was examined toward six amino acids by using Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR). The reactivity of the radicals studied was determined by the electrophilicity of the radical, which can be characterized by the radical's electron affinity (EA). The larger the electron affinity of the radical, the higher the overall reaction rate. In addition to the expected H-atom abstraction, several unprecedented reaction pathways were observed, including NH2 abstraction, SH abstraction, and SCH3 abstraction. These reaction pathways dominate for the most electrophilic radicals, and they may not follow radical but rather nucleophilic addition-elimination mechanisms. Hydrogen abstraction from glycine was also investigated theoretically. The results indicate that hydrogen abstraction from alphaC of glycine is both kinetically and thermodynamically favored over the NH2 group. The ordering of transition state energies for hydrogen abstraction from the alphaC and NH2 groups was found to reflect the radicals' EA ordering.

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Polar effects are demonstrated to play an important role in controlling the reactivity of polyaromatic sigma-radicals that are structurally related to the active intermediates of the enediyne anticancer type antibiotics. This was accomplished by measuring the rate constants of hydrogen atom abstraction for novel, charged dehydroquinolines, dehydroisoquinolines, dehydrobenzenes, and dehydronaphthalenes in the gas phase by using Fourier-transform ion cyclotron resonance mass spectrometry. The reactivity trends observed for these radicals upon hydrogen atom abstraction from tetrahydrofuran and 2-methyltetrahydrofuran, simple models of deoxyribose, do not reflect differences in reaction exothermicities, radical sizes, exact location of the radical site in the ring system, or heteroatom-radical site distances. However, the reactivity trends match the trend in the calculated electron affinities of the radicals. The radicals' different electrophilicities result in variations in the reaction barrier due to different extents of polarization of the transition state. Generally, the reaction efficiencies are the greatest when the formally charged heteroatom is contained within the same ring system as the radical site. In this case, polar effects have the greatest influence on radical reactivity. Hence, insertion of a basic heteroatom (which gets protonated in biological systems) into specific locations in the polyaromatic ring system of the sigma-biradicals, which ultimately cause cleavage of DNA exposed to the enediyne antitumor drugs, should allow tuning of the reactivity of these radicals.

A chemical ionization method is reported for distinction of diastereomeric hydroxysteroids by using Fourier-transform ion cyclotron mass spectrometry (FT-ICR). Certain phosphenium ions are demonstrated to react with stereoisomeric steroids to yield qualitatively different product ions. For example, 1,3,5(10)-estratriene-3,16␤,17␤-triol (cis-estriol) reacts with the dimethoxy phosphenium ion to form a diagnostic product ion (not formed for the trans-estriol) through addition followed by the loss of two molecules of methanol. In an analogous manner, the 1,3-dioxolan-2-phosphenium ion produces a diagnostic product ion through the loss of ethylene glycol from the adduct of cis-estriol only. The 1,3,5(10)-estratriene-3,16␣,17␤-triol (trans-estriol), on the other hand, reacts with each phosphenium ion only via hydroxide abstraction-initiated pathways that indicate the presence of at least two hydroxyl groups in the molecule. These specific reactions take place for all hydroxysteroids examined, independent of their stereochemistry. Another isomer pair, cholestan-3␣,5␣-diol (cis-cholestandiol) and cholestan-3␤,5␣-diol (trans-cholestandiol), is differentiated based on selective elimination of water only from the adduct of the cis-isomer. However, the method does not allow distinction between the stereoisomeric 5␤-pregnane-3␣,17␣,20␣-triol and 5␤-pregnane-3␣,17␣,20␤-triol. The different reactivities of the three pairs of steroid isomers and of each diastereomeric compound pair are rationalized by reaction enthalpies and steric effects based on straightforward and predictable reaction mechanisms. T he ability to distinguish stereoisomers of biologically active compounds is important since their reactivity is often greatly influenced by their stereochemistry. The need for fast, accurate, and specific methods for the determination of the stereochemical structures of compounds is especially important in the area of drug development because the activity of a drug depends greatly upon its three-dimensional structure [1]. HPLC is commonly used for this task, but long analysis times and the lack of standards for unknown compounds are some of the drawbacks of this technique [2]. Stereoisomer differentiation by mass spectrometry offers several advantages, including speed, sensitivity, and the ability to obtain structural information for unknown compounds in complex mixtures. As a result, many research efforts have focused on the development of mass spectrometric approaches for the analysis of stereoisomers [3][4][5][6][7][8] . The ability to differentiate these types of compounds is important because amino and hydroxyl groups are some of the most common functional groups present in biological molecules and natural products.Electron ionization mass spectrometry is widely used to obtain structural information on molecules but it is insensitive to their stereochemical structure. For example, the electron ionization mass spectra of cis -and trans-1,2-cyclopentanediols [3a] and cis-and trans-1,2-diaminocyclohexanes [5] are identical. ...