Brett M. Showalter

Hydrolytic Reactivity Trends among Potential Prodrugs of the O2-Glycosylated Diazeniumdiolate Family. Targeting Nitric Oxide to Macrophages for Antileishmanial Activity

Glycosylated diazeniumdiolates of structure R2NN(O)=NO−R′ (R′ = a saccharide residue) are potential prodrugs of the nitric oxide (NO)-releasing but acid-sensitive R2NN(O)=NO− ion. Moreover, cleaving the acid-stable glycosides under alkaline conditions provides a convenient protecting group strategy for diazeniumdiolate ions. Here, we report comparative hydrolysis rate data for five representative glycosylated diazeniumdiolates at pH 14, 7.4, and 3.8−4.6 as background for further developing both the protecting group application and the ability to target NO pharmacologically to macrophages harboring intracellular pathogens. Confirming the potential in the latter application, adding R2NN(O)=NO−GlcNAc (where R2N = diethylamino or pyrrolidin-l-yl and GlcNAc = N-acetylglucosamin-l-yl) to cultures of infected mouse macrophages that were deficient in inducible NO synthase caused rapid death of the intracellular protozoan parasite Leishmania major with no host cell toxicity.

Identification of a Vibrational Frequency Corresponding to H‐atom Translocation in Hypericin¶

Using time‐resolved infrared spectroscopy, ab initio quantum mechanical calculations and synthetic organic chemistry a region in the infrared spectrum of triplet hypericin has been found between 1400 and 1500 cm−1 corresponding to the translocation of the hydrogen atom between the enol and the keto oxygens, O···H···O. This result is discussed in the context of the photophysics of hypericin and of eventual measurements to observe directly the excited‐state H‐atom transfer.

Time-resolved IR studies of cyclic enone triplet excited states and their reactions with alkenes

The ππ* triplet excited states of 3-phenyl-2-cyclohexenone (1) and 3-phenyl-2-cyclopentenone (2) have been observed by time-resolved infrared (TRIR) spectroscopy. The reaction of various alkenes with the triplet excited state of 2 has also been studied by TRIR spectroscopy, and the partitioning between fragmentation and ring closure of the biradical intermediates involved has been estimated. Within a series of structurally related biradicals, more stable ones undergo ring closure more efficiently.

Time‐resolved infrared studies of triplet 1,3‐cyclopentanediyl

Triplet-sensitized photolysis of 2,3-diazabicyclo[2.2.1]hept-2-ene (1) in argon- or oxygen- saturated acetonitrile-d3 solutions results in the formation of bicyclo[2.1.0]pentane (3), a ring closure product arising from an intermediate 1,3-cyclopentanediyl triplet biradical (2). Time-resolved infrared (TRIR) spectroscopy was used to monitor the kinetics of bicyclopentane 3 production. This analysis provides a measurement of the triplet biradical lifetime and an estimate of the bimolecular reaction rate between biradical 2 and oxygen, both in good agreement with previous investigations. Our studies also indicate that certain IR bands due to 3 in the C–H stretching region overlap with corresponding bands in biradical 2. This interpretation is supported by computational investigations.Copyright