Mechanistic classification

M. T. M. (1999) Mechanistic classification of electrochemical oscillators - operational experimental strategy./. Electroanal. Chem, 478, 50-66. 

In Chapter 10 of Part A, the mechanistic classification of 1,3-dipolar cycloadditions as concerted cycloadditions was developed. Dipolar cycloaddition reactions are useful both for syntheses of heterocyclic compounds and for carbon-carbon bond formation. Table 6.2 lists some of the types of molecules that are capable of dipolar cycloaddition. These molecules, which are called 1,3-dipoles, have it electron systems that are isoelectronic with allyl or propargyl anions, consisting of two filled and one empty orbital. Each molecule has at least one charge-separated resonance structure with opposite charges in a 1,3-relationship, and it is this structural feature that leads to the name 1,3-dipolar cycloadditions for this class of reactions.136... 

There are, however, also many examples of mixed domino processes , such as the synthesis of daphnilactone (see Scheme 0.6), where two anionic processes are followed by two pericydic reactions. As can be seen from the information in Table 0.1, by counting only two steps we have 64 categories, yet by including a further step the number increases to 512. However, many of these categories are not - or only scarcely - occupied. Therefore, only the first number of the different chapter correlates with our mechanistic classification. The second number only corresponds to a consecutive numbering to avoid empty chapters. Thus, for example in Chapters 4 and 6, which describe pericydic and transition metal-catalyzed reactions, respectively, the second number corresponds to the frequency of the different processes. 

The mechanistic classification generally accepted for ligand substitution reactions was proposed by Langford and Gray in 1965 (19). This classification was often discussed in the literature and its principles are only summarized here for convenience. 

Mechanistic classification system, 13 441 Mechanistic kinetic expressions, 10 85-88 Mechanistic organic chemistry, high... 

Attempts to improve the simple mechanistic classification have been made using More-O Ferall diagrams, or transition state bond order variations. ... 

Langford and Gray proposed in 1965 (13) a mechanistic classification for ligand substitution reactions, which is now generally accepted and summarized here for convenience. In their classification they divided ligand substitution reactions into three categories of stoichiometric mechanisms associative (A) where an intermediate of increased coordination number can be detected, dissociative (D) where an intermediate of reduced coordination number can be detected, and interchange (I) where there is no kinetically detectable intermediate [Eqs. (2)-(4)]. In Eqs. (2)-(4), MX -i and... 

LCischer C, Ungless MA The mechanistic classification of addictive drugs. PLoS Med 2006 3 e437. 

The base-promoted elimination of quaternary ammonium ions (Hofmann elimination) has been proposed to proceed by an E2-like mechanism. Tell how each of the following observations supports this mechanistic classification. Be specific about exactly what each piece of information reveals. 

Mechanistic classification of inorganic redox processes 86 Mechanistic classification of organic redox processes 86 Synthetic classification of organic electron-transfer reactions 90... 

Secondly, a mechanistic classification scheme is necessary to narrow down a vast and ill-defined subject matter to a manageable size with a consistent content. Moreover, we will here have to take the first steps in transferring inorganic concepts into organic ones. Whatever we may think of nomenclature and definitions, science would not exist without them. 

Chapter 6 reveals how we are going to subdivide organic chemistry. We shall use a mechanistic classification rather than a structural classification and explain one type of reaction rather than one type of compound in each chapter. In the rest of the book most of the chapters describe types of reaction in a mechanistic way. Here is a selection. 

Referring to a mechanistic classification of organocatalysts (Seayad and List 2005), currently the two most prominent classes are Brpnsted acid catalysts and Lewis base catalysts. Within the latter class chiral secondary amines (enamine, iminium, dienamine activation for a short review please refer to List 2006) play an important role and can be considered as—by now—already widely extended mimetics of type I aldolases, whereas acylation catalysts, for example, refer to hydrolases or peptidases (Spivey and McDaid 2007). Thiamine-dependent enzymes, a versatile class of C-C bond forming and destructing biocatalysts (Pohl et al. 2002) with their common catalytically active coenzyme thiamine (vitamin Bi), are understood to be the biomimetic roots ofcar-bene catalysis, a further class of nucleophilic, Lewis base catalysis with increasing importance in the last 5 years. 

With regard to a mechanistic classification of the known carbene-catalyzed processes, a further subdivison of these two major classes might be useful. Scheme 4 provides an attempt at a mechanism-based classification. 

Cullen, J.M. (2005). Mechanistic classification of liver injury. Toxicol. Pathol. 33 6-8. 

Eiswirth M, Freund A, Ross J (1991b) Mechanistic classification of chemical oscillators and the role of spedes. Adv Chem Phys 80 127-198... 

FIGURE 17.6 Mechanistic classification of biomarkers interposed betwreen drug administration and observed therapeutic or toxic clinical effects. (Further explanation is provided in the text.)... 

Most electrochemical studies carried out today make use of online computers for control of experiments and for data acquisition and analysis, including the techniques described earlier. Examples of the application of computer evaluation of experimental results include, for instance, pattern recognition [151] and the recording of current-time profiles of the form A(lni)/A(lnt) versus t for mechanistic classification [152] as well as nonlinear regression techniques [153-155]. Efforts have also been made to use knowledge-based systems for the elucidation of reaction mechanisms [156]. 

The substitution reactions of organometallic compounds, in which heterolytic attack at the carbon is usually by electrophiles, are not susceptible to the simple mechanistic classification (SnI, Sn2, and S i) which is so useful in discussing nucleophilic reactions of organo-nonmetallic compounds. The situation is complicated by the propensity of the metal to increase its coordination number, and a spectrum of mechanisms has to be considered in which electrophilic attack at carbon is accompanied by or preceded by nucleophilic attack at the metal. 

TaMe 8.2 Mechanistic Classification of Antidepressants and Other Types of Agents/Mechanisms Currently Being Explored for the Treatment of Depression... 

Some operational classifications of antagonism relate solely to certain molecular mechanisms. For example, allosteric antagonists produce saturable effects (i.e., a maximum antagonism is produced, after which further increases in antagonist concentration have no further effect). However, operational effects on dose-response curves do not always unambiguously indicate a molecular mechanism in that experiments can reveal combinations of compatible operational and mechanistic classifications (i.e., an allosteric molecular mechanism can produce either surmountable or insurmountable effects on dose-response curves depending on the system). Finally, since allosteric effects produce a change in shape of the receptor, it cannot be assumed a priori... 

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