Light-Activated Rhenium Complexes with Dual Mode of Action against Bacteria

New antibiotics and innovative approaches to kill drug-resistant bacteria are urgently needed. Metal complexes offer access to alternative modes of action but have only sparingly been investigated in antibacterial drug discovery. We have developed a light-activated rhenium complex with activity against drug-resistant S. aureus and E. coli. The activity profile against mutant strains combined with assessments of cellular uptake and synergy suggest two distinct modes of action.     

Gas-phase pyrolysis mechanism and kinetics of 3-t-butoxyquadricyclane

The gas-phase pyrolysis of 3-t-butoxyquadricyclane [1] was investigated over the temperature range 511–542 K at one atm in helium. The initial pyrolysis step is the isomerization of 3-t-butoxyquadricyclane to 7-t-butoxynorbornadiene (Ea = 38.49 ± 0.85 kcal/mole, log A = 15.44 ± 0.35). 7-t-butoxynorbornadiene exhibits a single unimolecular reaction pathway which produces a mixture of t-butoxycycloheptatrienes (Ea = 38.44 ± 0.63 kcal/mole, log A = 15.05 ± 0.26). This two-step mechanism affords fewer reactions than unsubstituted quadricyclane in the gas phase and could be useful for its reduced sooting potential. © 1996 John Wiley & Sons, Inc.     

Charge transfer complexes of some N-methylated thiohydantoins with molecular iodine

Using a series of N-methylated thiohydantoins as substrates, the donor properties of the sulfur atom are measured by determining the stability constants (K) of their adducts with molecular iodine. The K's have been determined by recording the UV-visible spectra of several CH₂Cl₂ solutions with different amounts of the reagents. The experimental data fit the 1:1 adduct model for all the compounds. The K values, compared with those previously found for the unsubstituted hydantoins and with those obtained for 5-methyl-2-thiohydantoin, show that the hydrogen-bonding interaction between the NH hydrogen and the S-bonded iodine plays an important role in determining the stability of the adduct. The K values obtained for several pentaatomic rings, all containing the thioureido group  HN C() NH , are discussed on the basis of the influence of the substituents at C-4 and C-5 on the donor properties of the sulfur atom.     

Effects of Cations on HPTS Fluorescence and Quantification of Free Gadolinium Ions in Solution; Assessment of Intracellular Release of Gd3+ from Gd-Based MRI Contrast Agents

8-Hydroxypyrene-1,3,6-trisulfonate (HPTS) is a small, hydrophilic fluorescent molecule. Since the pKa of the hydroxyl group is close to neutrality and quickly responds to pH changes, it is widely used as a pH-reporter in cell biology for measurements of intracellular pH. HPTS fluorescence (both excitation and emission spectra) at variable pH was measured in pure water in the presence of NaCl solution or in the presence of different buffers (PBS or hepes in the presence or not of NaCl) and in a solution containing BSA. pKa values have been obtained from the sigmoidal curves. Herein, we investigated the effect of mono-, di-, and trivalent cations (Na⁺, Ca²⁺, La³⁺, Gd³⁺) on fluorescence changes and proposed its use for the quantification of trivalent cations (e.g., gadolinium ions) present in solution as acqua-ions. Starting from the linear regression, the LoD value of 6.32 µM for the Gd³⁺ detection was calculated. The effects on the emission were also analyzed in the presence of a combination of Gd³⁺ at two different concentrations and the previously indicated mono and di-valent ions. The study demonstrated the feasibility of a qualitative method to investigate the intracellular Gd³⁺ release upon the administration of Gd-based contrast agents in murine macrophages.     

The mechanism of Sandmeyer's cyclization reaction by electrospray ionization mass spectrometry

Using electrospray ionization (tandem) mass spectrometry (ESI-MS(/MS)) spectrometric experiments, the Sandmeyer reaction was monitored on-line, and key intermediates were intercepted and characterized for the first time. The mechanistic information provided by on-line ESI-MS(/MS) is in accordance with Sandmeyer's proposal, and was made possible by coupling a microreactor on-line to the ESI ion source, which allowed reactions to be screened from 0.7-2.0 s, identifying and characterizing all intermediates that were formed and consumed during the reaction.     

Negative ion tandem mass spectrometry of leukotriene E4, and LTE4, metabolites: Identification of LTE4, in human urine

The sulfidopeptide leukotrienes, leukotriene E₄, (LTE₄,) and its N-acetyl derivative and several ω? and β-oxidized metabolites of LTE₄, have been analyzed by tandem mass spectrometry. [M?H]^? ions were produced by continuous flow fast atom bombardment, and collision-induced dissociation of these ions was studied by using a triple quadrupole instrument. The product ion spectra obtained were characteristic of the structure of LTE₄, and mechanisms of ion formation were investigated by using deuterated compounds. β-Elimination of the peptide portion of LTE₄, by loss of CO₂, and ethylene amine leaves the C-l carboxyl group ionized in the most abundant fragment ion for LTE₄, and all metabolites. Tandem mass spectrometry of fast atom bombardment-generated anions from ω? and β-oxidized metabolites of LTE₄, produced similar ions with only a minor influence of the third carboxyl group at the omega terminus evident. Tandem mass spectrometry was used to identify unequivocally the presence of unmodified LTE₄, in a high performance liquid chromatography-purified fraction of urine from a normal healthy volunteer after infusion with LTE₄.     

Interplay of information quantifiers and the modified Jaynes-Cummings model

The dynamics of the Buck and Sukumar model (B. Buck and C. V. Sukumar, Phys. Lett. A 81, 132 (1981)) is investigated using different semi-classical information-theory tools. Their interplay reveals somewhat unexpected features. A new signature for the classical-quantum barrier is encountered thereby.     

Synthesis of side‐chain‐substituted ifosfamide analogs

Three analogs of the cytostatic drug ifosfamide incorporating 1‐methyl‐2‐chloroethyl side chains were designed and prepared as an attempt to obtain drugs of lower toxicity.