Ruthenium polypyridyl complexes and their modes of interaction with DNA : is there a correlation between these interactions and the antitumor activity of the compounds?

Various interaction modes between a group of six ruthenium polypyridyl complexes and DNA have been studied using a number of spectroscopic techniques. Five mononuclear species were selected with formula [Ru(tpy) L1L2](2-n)?, and one closely related dinuclear cation of formula [{Ru(apy)(tpy)}2{l-H2N(CH2)6NH2}]4?. The ligand tpy is 2,20:60,200-terpyridine and the ligand L1 is a bidentate ligand, namely, apy (2,20-azobispyridine), 2-phenylazopyridine, or 2-phenylpyridinylmethylene amine. The ligand L2 is a labile monodentate ligand, being Cl-, H2O, or CH3CN. All six species containing a labile L2 were found to be able to coordinate to the DNA model base 9-ethylguanine by 1H NMR and mass spectrometry. The dinuclear cationic species, which has no positions available for coordination to a DNA base, was studied for comparison purposes. The interactions between a selection of four representative complexes and calf-thymus DNA were studied by circular and linear dichroism. To explore a possible relation between DNA-binding ability and toxicity, all compounds were screened for anticancer activity in a variety of cancer cell lines, showing in some cases an activity which is comparable to that of cisplatin. Comparison of the details of the compound structures, their DNA binding, and their toxicity allows the exploration of structure–activity relationships that might be used to guide optimization of the activity of agents of this class of compounds

Aromaonderzoek in de lift

Verslag van het in mei gehouden minisymposium te Wageningen. Het werd georganiseerd door de Vereniging voor Voedingsleer en Levensmiddelentechnologi

Aromaonderzoek in de lift

Verslag van het in mei gehouden minisymposium te Wageningen. Het werd georganiseerd door de Vereniging voor Voedingsleer en Levensmiddelentechnologi

Effects of bite size and duration of oral processing on retro-nasal aroma release - features contributing to meal termination

The brain response to a retro-nasally sensed food odour signals the perception of food and it is suggested to be related to satiation. It is hypothesised that consuming food either in multiple small bite sizes or with a longer durations of oral processing may evoke substantial oral processing per gram consumed and an increase in transit time in the oral cavity. This is expected to result in a higher cumulative retro-nasal aroma stimulation, which in turn may lead to increased feelings of satiation and decreased food intake. Using real-time atmospheric pressure chemical ionisation-MS, in vivo retro-nasal aroma release was assessed for twenty-one young, healthy and normal-weight subjects consuming dark chocolate-flavoured custard. Subjects were exposed to both free or fixed bite size (5 and 15 g) and durations of oral processing before swallowing (3 and 9 s) in a cross-over design. For a fixed amount of dark chocolate-flavoured custard, consumption in multiple small bite sizes resulted in a significantly higher cumulative extent of retro-nasal aroma release per gram consumed compared with a smaller amount of large bite sizes. In addition, a longer duration of oral processing tended to result in a higher cumulative extent of retro-nasal aroma release per gram consumed compared with a short duration of oral processing. An interaction effect of bite size and duration of oral processing was not observed. In conclusion, decreasing bite size or increasing duration of oral processing led to a higher cumulative retro-nasal aroma stimulation per gram consumed. Hence, adapting bite size or duration of oral processing indicates that meal termination can be accelerated by increasing the extent of retro-nasal aroma release and, subsequently, the satiation

Enhancing LC×LC separations through Multi-Task Bayesian Optimization

Method development in comprehensive two-dimensional liquid chromatography (LC×LC) is a challenging process. The interdependencies between the two dimensions and the possibility of incorporating complex gradient profiles, such as multi-segmented gradients or shifting gradients, make trial-and-error method development time-consuming and highly dependent on user experience. Retention modeling and Bayesian optimization (BO) have been proposed as solutions to mitigate these issues. However, both approaches have their strengths and weaknesses. On one hand, retention modeling depends on effective peak tracking and accurate retention time and width predictions, becoming increasingly challenging for complex samples and advanced gradient assemblies. On the other hand, Bayesian optimization may require many experiments when dealing with many adjustable parameters, as in LC×LC. Therefore, in this work, we investigate the use of multi-task Bayesian optimization (MTBO), a method that can combine information from both retention modeling and experimental measurements. The algorithm was first tested and compared with BO using a synthetic retention modeling test case, where it was shown that MTBO finds better optima with fewer method-development iterations than conventional BO. Next, the algorithm was tested on the optimization of a method for a pesticide sample and we found that the algorithm was able to improve upon the initial scanning experiments. Multi-task Bayesian optimization is a promising technique in situations where modeling retention is challenging, and the high number of adjustable parameters and/or limited optimization budget makes traditional Bayesian optimization impractical