Poor experimental question

Too often results are compromised by a poor experimental set-up of the studies and nontransparent data. Even essential information such as the relevant physicochemical characteristics of the drug in relation to the chosen aerosol system or the fraction that is deposited in the alveoli is often not provided. This makes it impossible to evaluate the impact of such studies. As a result, it is unclear until now to what extent and at what rate macromolecular drugs (> 20 kDa) can be absorbed by the lung. Moreover, the routes by which macromolecules pass through the different pulmonary membranes, especially the alveolar membrane, are unknown. Appropriate experiments and models that provide adequate answers to these questions are required in the coming years. 

As noted, the alkaloid yield from the Beocin plants was low, which the authors suggested might be caused by the poor soil in which the plants were growing (Popovic et ah, 1992). One could ask whether the soil conditions to which they refer might be influential in the overall alkaloid biosynthetic processes in this species. It would be of interest to see experimental studies aimed at determining the effect of soil components on these processes. In the present case, it may be a lack of, or reduction in the activity of, the oxidase(s) necessary for the dimerization process (required to form the bibenzyldihydroisoquinolines) to occur. It is also possible that the lack of dimeric alkaloids may simply reflect a concentration effect caused by the edaphic conditions. These questions should be accessible to experiment. 

Note that it is highly desirable that the identity of every sample is confirmed before analysis, and that samples are adequately pure for the measurement in question. In the pH-metric methods, the sensor is a pH electrode and cannot distinguish between analyte and impurity. In the methods that depend on UV absorbance, if a sample contains an impurity with stronger absorbance than the sample, then the calculation of results from experimental data is complicated. Combinatorial samples are by nature poorly characterized, and even in the chromatographic methods in which analyte and impurity will be separated, it may be difficult to assign the peaks unambiguously. It is therefore advisable to purify samples before they are submitted for analysis of log D and pKa. 

In the course of investigation of reactivity of the mesoionic compound 44 (Scheme 2) the question arose if this bicyclic system participates in Diels-Alder reactions as an electron-rich or an electron-poor component <1999T13703>. The energy level of the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) orbitals were calculated by PM3 method. Comparison of these values with those of two different dienophiles (dimethyl acetylenedicarboxylate (DMAD) and 1,1-diethylamino-l-propyne) suggested that a faster cycloaddition can be expected with the electron-rich ynamine, that is, the Diels-Alder reaction of inverse electron demand is preferred. The experimental results seemed to support this assumption. 

Many lethality data exist for a variety of species (mouse, rat, guinea pig, rabbit, cat, dog, goat, sheep, and monkeys). However, in most cases, experimental parameters are poorly described, and the quality of the data is questionable for AEGL derivation. The mouse and rat LC50 studies of Zwart et al. (1990) are the exception and are appropriate for AEGL-3 derivation. 

This study employs HF theory to answer only very qualitative questions, which is appropriate given the typically rather poor accuracy of the model in the absence of accounting for electron correlation. Future use of HF/3-21G to predict Q values for monomers not yet experimentally characterized might be worthwhile, but quantitative differences between monomers should not be taken particularly seriously except to the extent they may be categorized as large, medium, or small. 

The value of the kinetic isotope effect method lies mainly in the possibility of making a substitution within tlve reactive center of the molecule, while still retaining the original type of the read ion, thus allowing the cancellation of many poorly defined quantities in the absolute rate equations and permitting a direct comparison between the measured and calculated values of the relative rate constants. Since the magnitude of these latter values depends on the hypothetical transition state model, a diagnostic means is provided by the method for the experimental verification of the nature of tlie transition state in question. 

Various forms of distorted-wave approximation have been used to investigate the excitation cross sections in helium. Parcell, McEachran and Stauffer (1983, 1987) used this approximation to investigate the 2 S and 21 P excitation of helium over the energy range from near the threshold up to 150 eV. Their results for the 21 S excitation were found to be in rather poor agreement with the corresponding experimental results of Sueoka (1982), which prompted Parcell, McEachran and Stauffer (1987) to question whether these measurements were for this transition alone,... 

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