Topotecan dynamics,tautomerism and reactivity—1H/13C NMR and ESI MS study

Topotecan (TPT) is in clinical use as an antitumor agent, hycamtin^?. Because of this, it requires both biologically and chemically useful information to be available. TPT acts by binding to the covalent complex formed by nicked DNA and topoisomerase I. This has a poisonous effect since inserted into the single‐strand nick and TPT inhibits its religation. We used NMR to trace TPT dynamics, tautomerism and solvolysis products in various solvents and conditions. Chemical stability was assessed in methanol and DMSO as compared to water, and the regioselectivity of the N‐ and O‐methylation was studied using various alkylating agents. The reaction products of quaternization of the nitrogen atom and methylation of the oxygen atom were characterized by means of ESI MS, ¹H/¹³C‐HMBC and ‐HSQCAD NMR. We have focused on the NMR characterization of TPT with an anticipation that its aggregation, tumbling properties and the intramolecular dipolar interactions will be a common feature for other compounds described in this article. These features can also be useful in tracing the interactions of this class of topoisomerase I (TopoI) poisons with DNA. Moreover, the results explained shed light on the recently disclosed problem of lack of stability of TPT in the heart tissue homogenate samples using the analytical assays developed for this class of compounds carried out in the presence of methanol. Copyright © 2010 John Wiley & Sons, Ltd.     

Construction of the tricyclic 5-7-6 scaffold of fungi-derived diterpenoids. Total synthesis of (±)-heptemerone G and an approach to Danishefsky's intermediate for guanacastepene A synthesis

An efficient and operationally simple synthesis of the neodolestane diterpenoids (±)-heptemerone G and (±)-guanacastepene A is reported. The common tricyclic scaffold (±)-4 was prepared from 2-methylcyclopent-2-en-1-one via 23 isolated intermediates in 5.1% yield. The key features include a novel annulation sequence combining tandem conjugate addition, methylenation, and metathesis reaction and completely diastereoselective transformation of the azulene derivative 23 into rings AB building block 32. Stereochemistry of alkylation of both saturated trans-azulene enolate 38 and its α,β-unsaturated counterpart 48 was examined. Rather surprisingly, a different facial selectivity was recorded. Several synthetic methods were modified or developed, including an alternative methodology for the Wharton-type rearrangement, ketalization of epimerizable ketone under mild conditions, and efficient alkylation of a ketone via its kinetic enolate.     

Studies on the uptake of different arsenic forms and the influence of sample pretreatment on arsenic speciation in White mustard (Sinapis alba)

The concentration and speciation of arsenic incorporated by plants grown in the presence of different arsenic compounds was compared, and the influence of plant sample pretreatment and extraction procedures on the recovery and reliability of speciation analyses was studied. It was concluded that sample pretreatment greatly affected the extraction efficiency, but did not change arsenic speciation. The most suitable extraction procedure involved dried plant material without the use of liquid nitrogen. To assess the ability of White mustard to uptake arsenic in different forms, samples were cultivated in nutrient solutions containing either As(III), As(V), monomethylarsonic acid (MMA) or dimethylarsinic acid (DMA). The translocation factor was the highest (0.70) when DMA was added to the nutrient solution, however the overall As concentration in plant tissues was the lowest in this case. Only inorganic As was found in plant tissues when either As(III) or As(V) was added to the nutrient solution. When organic arsenic was present in the nutrient medium, however, it was partially transformed by the plants into inorganic forms.     

Structural changes accompanying excited-state electron transfer in meta- and para-dialkylaminopyridines

The electronic structure of the lowest excited singlet states and molecular geometries of a series of dialkylaminopyridines (DAAPs) representing electron donor–acceptor systems were studied by photostationary and time-resolved UV–vis spectroscopic methods and quantum chemical calculations. The comparative studies allow us to rationalize dual luminescence of 4-DAAPs in terms of the TICT state model—the analysis of the electronic transition dipole moments indicates a nearly orthogonal conformation of the fluorescent ICT states. Introduction of the amino group at meta position as in 3-diisopropylaminopyridine completely changes photophysics of these pyridine derivatives: (i) the Franck-Condon excited state initially reached upon excitation and the solvent equilibrated fluorescent state are most probably of the same nature (both excited states do not correspond to a full separation of charges) and (ii) the electronic structure and geometry of the fluorescent CT states of m-DIAP are solvent dependent.     

Bis(tetraethylammonium) tetrabromocobaltate(II) and bis(tetrabutylammonium) tetrabromomanganate(II): structure and magnetic properties

The crystal structures of tetrabromocobaltate(II) and tetrabromomanganate(II) salts of general formula [(C₂H₅)₄N]₂[CoBr₄] (1) and [(C₄H₉)₄N]₂[MnBr₄] (2) were determined. The manganese and cobalt cations are four-coordinated by bromide anions and they adopt a slightly distorted tetrahedral coordination. In the structure of both compounds there are neither hydrogen bonds nor any unusual short-range intermolecular interactions. Magnetic measurements of the powdered samples gave negative values of the Weiss constants equal to −4.9 and −1.1 K for (1) and (2), respectively, which suggest antiferromagnetic interactions to be transferred within the crystal lattice.     

Structure and properties of the low-lying electronic states of CeC(2) and CeC(2)(+)

Theoretical studies on the electronic and thermodynamic properties of several electronic states of CeC(2) and CeC(2)(+) have been carried out employing state-of-the-art single- and multireference techniques. The ground and the low-lying electronic states of these two species have been found to possess C(2v) triangular structures. A (3)B(2) state has been found to be the ground state of CeC(2) while for CeC(2)(+) (2)A(2) is the ground state. The computed electron ionization energy is in excellent agreement with experiment. The experimentally observed thermodynamic properties (dissociation and atomization energies) of reactions involving CeC(2) dissociation are corrected using the computed gas-phase properties of the molecule and the partition functions. The bent triplet and singlet state of CeC(2) exhibit large dipole moments (7.0-10.5 D) and it is consistent with the ionic character (through dative charge transfer) of the cluster in ground and excited states.     

A practical guide to nano-LC troubleshooting

Capillary LC is one of the most powerful analytical tools available for separation scientists. Its unique analytical properties are associated with numerous technical issues that may cause operation of such systems to be somehow troublesome. Because of that, a good experience in capillary LC troubleshooting is required to keep the system in shape and, in effect, to obtain reliable results. In this paper, we summarize the most important issues of the capillary systems, including void and dead volumes, leakages, sample injection, and a multidimensional LC approach. The aim of this paper was to provide practical advise on system diagnosis, and to present solutions to problems discussed. Also, several exemplary nano-LC separations are included to demonstrate some typical problems encountered in our daily work.