Optimization of a liquid chromatographic separation for the simultaneous determination of four anthracyclines and their respective 13-S-dihydro metabolites

The optimization of a liquid chromatographic separation of four anthracyclines (doxorubicin, epirubicin, daunorubicin and idarubicin) and their respective 13-S-dihydro metabolites (doxorubicinol, epirubicinol, daunorubicinol and idarubicinol) is described. Inclusion of epidaunorubicin in the assay allows internal standardization. Potential chromatographic interference of aglycones (doxorubicinone, daunorubicinone, idarubicinone, doxorubicinolone, daunorubicinolone and idarubicinolone) was investigated and tackled. The analyses were performed on a C18 RP column and gradient elutions were performed with a mixture of 0.1% formic acid in water and 0.1% formic acid in ACN. The analytes were measured by fluorescence detection with an excitation wavelength of 480 nm and emission wavelength of 555 nm, respectively. The separation will potentially allow a broad field of applications, ranging from therapeutic drug monitoring and kinetic studies in cancer patients to monitoring hospital personnel and effluents.     

Symmetry-dependent solvation of donor-substituted triarylboranes

Donor-substituted triarylboranes are investigated by femtosecond absorption spectroscopy to study the influence of molecular symmetry on solvation. In solvents of varying polarity and differently fast solvation response, the solvation dynamics of a highly symmetric triple carbazole-substituted triarylborane (TCB) is compared to a single carbazole-substituted triarylborane (CB). The decomposition of the transient absorption spectra allows us to measure the solvation time by means of the time-dependent solvatochromic shift of the excited-state absorption (ESA) and the stimulated emission (SE). For all polar solvents under study we find an accelerated solvation process for TCB compared to the less symmetric CB. The difference is particularly large for solvents with a slow response. In order to explain these findings we propose that the electronic excitation is mobile in the symmetric molecule and can change between the three carbazole chromophores probably by a hopping mechanism. The excited-state dipole moment of TCB can thereby respond to the solvent relaxation and changes its direction according to the local field of the solvation shell. Thus, in a symmetric solute the possibility of an intramolecular charge delocalization over equivalent sites accelerates the approach of the minimum-energy configuration.     

Quantum study of the absorption spectroscopy of bis(triarylamine) radical cations

Absorption spectra of bridged triarylamine radical cations are calculated quantum mechanically which extends our previous classical analysis (Lambert et al. J. Phys. Chem. A 2004, 108, 6474). A comparison between spectra determined within a diabatic and an adiabatic representation shows that under certain circumstances deviations occur. It is found that the latter are mainly caused by the Condon approximation for the dipole moments. The inclusion of vibrational degrees of freedom leads to an excellent agreement with experiment.     

Femtosecond dynamics of electron transfer in a neutral organic mixed-valence compound

In this article we report a femtosecond time-resolved transient absorption study of a neutral organic mixed-valence (MV) compound with the aim to gain insight into its charge-transfer dynamics upon optical excitation. The back-electron transfer was investigated in five different solvents, toluene, dibutyl ether, methyl-tert-butyl ether (MTBE), benzonitrile and n-hexane. In the pump step, the molecule was excited at 760 nm and 850 nm into the intervalence charge-transfer band. The resulting transients can be described by two time constant. We assign one time constant to the rearrangement of solvent molecules in the charge-transfer state and the second time constant to back-electron transfer to the electronic ground state. Back-electron transfer rates range from 1.5 × 10¹² s⁻¹ in benzonitrile through 8.3 × 10¹¹ s⁻¹ in MTBE, around 1.6 × 10¹¹ s⁻¹ in dibutylether and toluene and to 3.8 × 10⁹ s⁻¹ in n-hexane.     

Structure-activity relationships in cholapod anion carriers: enhanced transmembrane chloride transport through substituent tuning

Chloride transport by a series of steroid-based "cholapod" receptors/carriers was studied in vesicles. The principal method involved preincorporation of the cholapods in the vesicle membranes, and the use of lucigenin fluorescence quenching to detect inward-transported Cl-. The results showed a partial correlation between anion affinity and transport activity, in that changes at the steroidal 7 and 12 positions affected both properties in concert. However, changes at the steroidal 3-position yielded irregular effects. Among the new steroids investigated the bis-p-nitrophenylthiourea 3 showed unprecedented activity, giving measurable transport through membranes with a transporter/lipid ratio of 1:250 000 (an average of <2 transporter molecules per vesicle). Increasing transporter lipophilicity had no effect, and positively charged steroids had low activity. The p-nitrophenyl monourea 25 showed modest but significant activity. Measurements using a second method, requiring the addition of transporters to preformed vesicle suspensions, implied that transporter delivery was problematic in some cases. A series of measurements employing membranes of different thicknesses provided further evidence that the cholapods act as mobile anion carriers.     

Palladium-Catalyzed Hydroaminocarbonylation of Olefins with Aliphatic Amines without Additives

Palladium-catalyzed hydroaminocarbonylation reactions of olefins using aliphatic amines were performed under carbon monoxide atmosphere. Despite the strong basicity of the applied nucleophiles, the targeted amides were successfully synthesized in the absence of acidic additives. Styrene, oct-1-ene and isoprene were transformed to the corresponding amide isomers in moderate to good isolated yields under optimized reaction conditions. Various aliphatic amines were used as N-nucleophiles. The effect of chiral diphosphines on product distribution, that is, on chemo-, regio- and enantioselectivities was also studied. Plausible explanation was given for the additive-free hydroaminocarbonylation reaction.     

Synthesis and absolute configuration of a constitutionally-new [5.6] spiroacetal from B. tryoni (Queensland fruit fly)

A novel spiroacetal, (2S,6R,8S)-2-methyl-8-ethyl-1,7-dioxaspiro[5.6]dodecane (1), has been identified from the volatile secretions of female B. tryoni by mass spectral analysis and synthesis of an authentic, enantioenriched sample.     

Complete (1)H and (13)C assignments of the four major saponins from Dioscorea villosa (wild yam)

Complete (1)H and (13)C spectral assignments for the four major steroidal saponins isolated by methanolic extraction of the roots of Dioscorea villosa, collected in North Carolina, United States (in summer and autumn), are presented in this paper. The structures were determined by a combination of (1)H, (13)C and 2D NMR techniques and were found to be ((3beta,25R)-26-(beta-D-glucopyranosyloxy)-22-methoxyfurost-5-en-3-yl-O-beta-D-glucopyranosyl-(1 --> 3)-O-beta-D-glucopyranosyl-(1 --> 4)-O-[alpha-L-rhamnopyranosyl-(1 --> 2)]-beta-D-glucopyranoside (1) (or methyl parvifloside), ((3beta,25R)-26-(beta-D-glucopyranosyloxy)-22 methoxyfurost-5-en-3-yl-O-alpha-L-rhamnopyranosyl-(1 --> 2)-O-[beta-D-gluco- pyranosyl-(1 --> 4)]-beta-D-glucopyranoside (2) (or methyl protodeltonin), (3beta,25R)-spirost-5-en-3-yl-O-beta-D-glucopy ranosyl-(1 --> 3)-O-beta-D-glucopyranosyl-(1 --> 4)-O-[alpha-L-rhamnopyranosyl-(1 --> 2)]-beta-D-glucopyranoside (3) (or Zingiberensis saponin I) and (3beta,25R)-spirost-5-en-3-yl-O-alpha-L-rhamnopyranosyl-(1 --> 2)-O-[beta-Ds-glucopyranosyl -(1 --> 4)]-beta-D-glucopyranoside (4) (or deltonin).