Mechanistic relationships

Addition and elimination processes are the reverse of one another in a formal sense. There is also a close mechanistic relationship between the two reactions, and in many systems reaction can occur in either direction. For example, hydration of alkenes and dehydration of alcohols are both familiar reactions that are related as an addition-elimination pair. 

The key to a rational design process is establishing a set of mechanistic relationships that relate the configuration to its performance. Use of those mechanistic relationships is what distinguishes the structural designer from a dress designer. 

The term design-analysis is used to emphasize the essential, but not dominant, role of analysis in the overall structural design process. Analysis plays no role whatsoever in dress design (with the possible exception of the now-classical analysis of a strapless evening gown). However, engineering design of a structure must involve analysis in the form of mechanistic relationships. Those mechanistic relationships must be used to quantitatively determine how to create the structural capabilities and then to match them to the structural requirements. The dis-... 

Sometimes, there are just indirect mechanistic relationships, or the existence of completely independent transport paths (e.g., protonic charge carriers and electronic holes in oxides). Parasitic transport frequently limits the fuel-cell performance, and a mechanistic understanding is definitely useful in the development of separator materials. 

More recently oxazolines and oxazines (125) have been polymerised by cationic mechanisms, using methyl iodide and methyl p-toiuene sulphonate as initiators, and a discussion of these systems will be included because of the close mechanistic relationship with the other polymerisations. 

There is a mechanistic relationship too, as both reduction of a metal center and formation of a metal hydride may proceed through a hydroxycarbonyl intermediate (18) as in (34). 

Note that the BSAF is an empirical ratio and does not necessarily indicate a mechanistic relationship or route of exposure. 

The toxic effects associated with PCN exposures in humans and wildlife are, in general, characteristic of effects due to chlorinated hydrocarbons such as 2,3,7,8-TCDD. For instance, chloracne, vitamin A depletion, edema and liver damage have been observed in animals exposed to TCDD. The human toxicity and mechanistic relationship of PCNs to TCDD may be useful in understanding these classes of compounds. Particularly, acute and subacute exposures of humans and cattle to PCNs may provide important clues to the toxic effects at high levels for other dioxin-like compounds. 

The volatile components identified from the reaction of cystine and DMHF in aqueous medium are shown in Table I. 2,4-Hexanedione, 3,5-dimethyl-l,2,4-trithiolanes and thiophenes are the major compounds. The mechanistic relationship of the three thiophenones produced has been postulated (23). The major groups of volatile components identified from the reaction in the glycerol medium are 1,3-dioxolanes and thiazoles (Table II). 1,3-Dioxolanes are formed by the reaction of glycerol and the degraded carbonyls by ketal or acetal formations. Comparison of the reaction of cystine and DMHF in water and in glycerol is outlined in Table III. 

Supersaturation has been observed to affect contact nucleation, but the mechanism by which this occurs is not clear. There are data that infer a direct relationship between contact nucleation and crystal growth these data showed that the number of nuclei produced by an impact was proportional to the linear growth rate of the impacted face. This could indicate that the effect of supersaturation is to alter growth rates and, concomitantly, the characteristics of the impacted crystal faces alternatively, what appears to be a mechanistic relationship actually could be a result of both nucleation and growth depending upon supersaturation. 

Sensitivity analysis is useful not only because it provides insight for a decision-maker, but also because it assists a model developer in identifying which assumptions and inputs matter the most to the estimate of the assessment end-point. Therefore, sensitivity analysis can be used during model development to identify priorities for data collection, as well as to determine which inputs matter little to the assessment and thus need not be a significant focus of time or other resources. Furthermore, insights obtained from sensitivity analysis can be used to determine which parts of a model might be the focus of further refinement, such as efforts to develop more detailed empirical or mechanistic relationships to better explain variability. Thus, sensitivity analysis is recommended as a tool for prioritizing model development activities. 

The classification within this section is based on the structural (rather than the mechanistic) relationship between the starting materials and products. Mechanistically, all of the reactions considered in this section involve nucleophilic substitution as the first step, except for aromatic substitution via the aryne mechanism, which involves elimination followed by nucleophilic addition. 

Intestinal Blood Flow. The mechanistic relationship among intestinal blood flow and absorption, secretion, and metabolic activity of the intestinal mucosa is unclear. However, there is evidence that impaired intestinal blood flow rate correlates with a decrease in drug absorption rate. It has been postulated that reduced blood flow slows down the absorption rate... 

Conveniently, glycosyl hydrolases have recently been classified into over 70 families, which are further grouped into clans based on their amino acid sequence similarities, reflecting structural as well as mechanistic relationships [178]. 

As an alternative to amide formation, intramolecular cyclizadons involving the nitrilium ion lead to a variety of heterocyclic systems (Section 1.9.2). Since carbenium ions, or their equivalents, may be produced by means other than strong acid, a number of valuable extensions of the original reaction are possible (Section 1.9.3). In addition, nitrilium and imidate species are also available through other processes, implying that the Ritter reaction has close mechanistic relationships with other well-established reactions and with the chemistry of the isonitriles. These aspects are explored in Section 1.9.4. 

Shen, E. Kipper, M.J. Dziadul, B. Lim, M.-K. Narasimhan, B. Mechanistic relationships between polymer micro structure and drug release kinetics in bioerodible polyanhydrides. J. Control. Release 2002, 82 (1), 115-125. 

Making relevant scientific assumptions involves understanding the mechanistic relationship between drug treatment and observed responses. In the context of modeling the response surface, it is useful to think of clinical pharmacology as the combination of disease progress and drug action (13). 

This was a great step forward for risk assessment. First, a reasonable dose metric was chosen for which there was evidence of a close mechanistic relationship with the potential adverse outcome. Second, because of this understanding and the knowledge of the metabolism and pharmacokinetics, a PBPK model was constructed. This model enabled a quantification of the dose metric in different species and for different dosing and exposure regimens and routes. Thus interspecies and interdose extrapolations could be done more rationally and with less uncertainty. Third, because of the first two developments the risk assessment was based on mode of action hence the relevance of dose, exposure levels, and test species relevance was better understood and considered. As a result, the cancer potency for DCM was changed by close to an order of magnitude from the previous value. 

---