Chemical hypothesis

The sceptical chemist draws conclusions regarding chemical materials chiefly on the basis of quantitative chemical analysis which is the touchstone of all chemical hypothesis. 

Sprague, P.W. Automated chemical hypothesis generation and database searching with CATALYST. Perspect. Drug. Disc. Des. 1995, 3, 1-20. 

Historically, a first step towards resolution of this problem was taken by Slater in 1953 through his formulation of the chemical hypothesis [6]. Un-... 

Astruc C., Malosse C. and Errard C. (2001) Lack of intraspecific aggression in the ant Tetramorium bicarinatum a chemical hypothesis. J. Chem. Ecol. 27, 1229-1248. 

D.J. Thompson, A chemical hypothesis for arsenic methylation in mammals. Chem. Biol. Interact. 88 89, 1993. 

Sheridan RP, Nachbar RB, Bush BL (1994) Extending the trend vector The trend matrix and sample-based partial least squares. J Comp Aided Mol Des 8 323-340 Sprague PW (1995) Automated chemical hypothesis generation and database searching with CATALYST. Persp Drug Disc Design 3 1-20... 

No information was located regarding the mechanism by which tetryl enters the blood stream from the lungs, skin, or gastrointestinal tract, the mechanism by which tetryl is transported in the blood stream, or the mechanism of toxicity for tetryl. Earlier studies suggested that the cause of tetryl-induced dermatitis, which is the most common and widely studied adverse effect, may be both physical (direct irritation by sharp tetryl crystals) and chemical (by reacting with components of the skin) (Ruxton 1917). The chemical hypothesis was later advanced by others as well (Bain and Thompson 1954 Brownlie and Cumming 1946). Bain and Thompson (1954) specifically suggested that histamine release may result from a tetryl-induced sensitization reaction or from direct tetryl-induced release from mast cells. 

Early proposals concerning the mechanism of the energy-linked transhydrogenase reaction were based on the chemical hypothesis of oxidative phosphorylation [82] and visualized the involvement of high-energy intermediates of the type 1 X, NADH I, NADP I, etc. [29,46]. These proposals, however, just as the chemical hypothesis as a whole, had to be abandoned because of lack of experimental evidence. 

The chemical hypothesis proposes that the energy is conserved by the formation of high-energy intermediates as reducing equivalents pass from one carrier to the... 

A model reaction that supports the above mechanism is the glycolytic substrate-linked phosphorylation, which proceeds via a thiol ester prior to the formation of the phosphorylated intermediate (Chapter 13). Although the chemical hypothesis is consistent with the substrate-linked phosphorylation mechanism, it is deficient in explaining the oxidative phosphorylation in mitochondria for two reasons ... 

The addition of ATP to anaerobic or terminally inhibited mitochondria or submitochondrial particles containing succinate Eo = 0.03 V at pH 7) induces reduction of cjdiochrome bj 16,17,65 see also 6 6). The original concept of the possible mechanism of this phenomenon described by Wilson and Dutton 19) was that the Eo of cytochrome f T changes because of the formation of a high energy derivative which is the primary intermediate for site 2 energy conservation reaction in oxidative phosphorylation. However, there has been another possible mechanism presented in which ATP can induce reduction of cytochrome bx by the decrease in the effective redox potential Ek) of the cytochrome because of reversed electron flow 57) or of the abolition of an accessibility barrier between the substrate and the cytochrome 58). The former explanation would be favored by the chemical hypothesis of oxidative phosphorylation, while the latter is favorable for the chemiosmotic hypothesis. 

These refiections do not, however, disprove the hypothesis of accidental mutations, for which if necessary in the last resort a physico-chemical hypothesis could be devised. Part of the macro-molecular substance could possibly, as a result of some extremely rare kind of activation—by thermal energy, light quanta, or cosmic... 

The discovery of drug-resistance (discussed in Section 6.5) in Ehrlich s laboratories gave welcome support to his chemical hypothesis of absorption and combination. Ehrlich observed that those trypanosomes which were resistant to fThe term Selective Toxicity was born, long after Ehrlich s time, in 1940. 

Throughout this discussion of oxidative phosphorylation, we have assumed that the coupling mechanisms involve the formation of high-energy intermediates. This chemical hypothesis is not accepted by all the chemiosmotic hypothesis of oxidative phosphorylation was proposed by Mitchell in 1961, and in 1966 Boyer [148] proposed a new hypothesis involving conformation coupling. 

This brings me to the latest chapter in the field of oxidative phosphorylation and the current controversies on the mechanism of oxidative phosphorylation. Slater s formulations based on the mode of glyceraldehyde-3-phosphate dehydrogenase action became known as the chemical hypothesis. In 1961 Mitchell proposed a chemiosmotic hypothesis. ... 

The confirmation of one of the predictions of the so-called chemical hypothesis of oxidative phosphorylation inspired the active search for the postulated high-energy ( ) intermediates. Indeed, it was surprising how easy it appeared to be to prove their existence, but they seemed to run out through your fingers when you tried to grab them and isolate them. One by one claims were made, but were either withdrawn or shown by others to rest on artifacts. Not without justification, new claims were greeted with suspicion and you would now probably have to submit crystals of such an intermediate with your paper if you hoped to have it accepted for publication. 

P. W. Sprague, Perspect. Drug Discovery Design 3,1 (1995). Automated Chemical Hypothesis Generation and Database Seardiing with Catalyst... 

But this chemical hypothesis needed experimental proof. Relevant data accumulated since Claude Bernard s experiments showed that the myoneural junction possesses a spedfic chemical sensitivity which differs from both the sensitivity of the nerve and the sensitivity of the muscle. Du-Bois Reymond. Langley. Elliott. Dixon. Dale and many other brilliant investigators participated in these studies. 

Full experimental proof of the chemical hypothesis was first obtained in the experiments of Otto Loewi on isolated amphibian hearts. The stimulation of extra-cardial nerves caused the release of substances which reproduced the effect of nerve stimulation when applied to another heart The stimulation of the vagal nerve was shown to induce the release of a substance indistinguishable from acetylcholine (ACh) atropine prevents both the effect of vagal excitation and the effect of ACh on the heart but does not prevent the release of ACh from the nerve. An enzyme hydrolysing ACh was discovered, later called cholinesterase physostigmine (ese-rine) inhibits this enzyme and thus protects ACh from being destroyed. 

The chief virtue of a purely physical interpretation of anesthesia lies in the fact that it fits all forms of anesthesia by whatever means produced. This no chemical hypothesis can do. The mechanism of anesthesia as here set forth is not to be expressed as the coagulation of protoplasm but as gelatinization, or thixotropic setting, for the latter two processes unlike the first are readily reversible. Identical results are obtained when anesthesia or the cessation of protoplasmic movement is accomplished by mechanical (88) or electrical shock. 

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