Reasoning speculative

The phosphine oxide (40) has been confirmed as the product of the reaction of chlorodiphenylphosphine with trifluoroacetic acid.36 Reasonable speculation has been made about the pathway to (40), although the question of direct addition to the carbonyl oxygen of the ketophosphine oxide (41) remains unanswered,36 as indicated in Scheme 3. 

There are a number of findings suggesting that agents that facilitate elimination of protein carbonyls (by either proteolytic elimination or by enzymically mediated chemical reduction) may suppress neurodegenerative conditions in model systems (Botella et al., 2004). Consequently, as carnosine may also react with protein carbonyls, it is theoretically possible that it could suppress formation and /the reactivity of protein carbonyls in the brain. Whether carnosine participates in carbonyl reductase activity has not been investigated but it is also a reasonable speculation. 

The theories of the Ionian philosophers are not of the nature of scientific theories in the modern sense, for they were not intended as hypotheses to be tested by observation or experiment. They belong to the domain of speculation rather metaphysical than physical, but, let it be noted, very reasonable speculations such as the human mind must content itself with until more specific knowledge admits of scientific deduction. They were attempts to harmonize the evidence of the senses with the demands of human reason, without assuming the arbitrary acts of gods or devils as the causes of phenomena. In other words, they were attempts to account for the visible universe by process of natural law, rather than by supernatural agencies. 

Unfortunately, although several authors30 have studied the kinetics of the overall reaction, no conclusive results have been obtained since the system is not really suitable for study by the usual titration methods because of the very slow rate of reaction.31 It is, however, possible to make reasonable speculations regarding the rate-determining step on the basis of the reported results (Scheme 3). 

Although an extensive data set is not generated for early drug candidates, there are some studies that are typically conducted when a compound is still in the precli-nical (pre-Phase I) stage of development. In addition, other information can be reasonably speculated based on chemical structure, mechanism of action, and projection of dosage. 

The system consists of two parts. The first part involves using either available information from the drug development process or making reasonable speculations to characterize the potential hazards to the workforce from exposure to the compounds. The second step involves using that information to assess the risk of exposure and recommend controls that prevent exposure. There is more than one suitable control method that can control most exposure points, and several examples have been provided. Finally, case studies have been provided to demonstrate the effectiveness of some of these control methods. 

The details of the mechanism are not well understood yet. Reasonable speculations based on evidence from ESR measurements have been published by van Reijen and Cossee (17) and by Pecherskaya and Kazan-skii (15). Van Reijen and Cossee speculate that the active site in a chromium oxide-silica catalyst is a tetrahedrally coordinated chromium ion. They picture the Cr04 tetrahedron linked to the SiC>2 network by... 

A brief report has appeared in which a wild-type esterase from Pseudomonas fluorescens (PFE), which shows no activity in the hydrolysis of the ester 16 (Fig. 11.21), was subjected to mutagenesis using the mutator strain Epicurian coli XL 1-Red [83], This resulted in a variant which catalyzes the reaction with an ee of 25 %. The absolute configuration of the major product ((R)- or (S)-17) was not determined. Sequencing of the esterase-variant revealed that two point mutations, A 209D and L181V, had occurred. Since the structure of the enzyme is unknown, a detailed interpretation was not possible, although reasonable speculations were made. 

Niki, Brietenbrach, and Morris (184a) have estimated from limited preliminary data that the reaction of Me2S with OH proceeds at a rate similar to that observed for H2S. Thus it is possible that Me2S also has a short residence time. The products of such a reaction in the troposphere are not known, though one can reasonably speculate that oxidation products similar to those expected for HS would result. 

Used to identify structures, neither of these techniques is new although only since the 1980s has it been possible to make them practical. To follow the reaction path and build up knowledge on an atomic scale that would contribute directly to the design of catalysts is not quite there the time response needs to get down to the millisecond, and that, like so much else in fundamental science, depends on federal research programs. It is a reasonable speculation to suggest that methods such as the two referred to here will be in routine use in electrocatalytic studies well before 2050. 

Acetoxylation is commonly encountered in anodic oxidations in acetic acid or in solutions containing acetate ion (Eberson and Nyberg, 1976). Mechanistic studies have not been made, and explanations of anodic acetoxylation reactions in the literature are based on reasonable speculations and precedents from other anode... 

Work on mechanistic details is in progress, but the present transformation may result from a catalytic cycle that involves the transmetalation between the hydroxo-rhodium(I) 4 and arylboronic acid to give the arylrhodium(I) species 5, and the insertion of enone to the Ar-Rh bond. The hydrolysis of the rhodium(I) enolate with water reproduces the hydroxorhodium species, as shown in Figure 1. The arylrhodium(I) complexes are unstable such as to preclude isolation in pure form, but they have been reasonably speculated to be the key intermediates carrying out various coupling reactions with organic halides and the addition to alkenes and alkynes. 

The chapter concentrates on those reactions where the mechanism is at least partly understood, for a wholly pragmatic reason speculative comments on the origin of enantioselection are hardly justified if the catalytic pathway is ill-defined. 

The functions of several plasma apolipoproteins are not known. ApoA-IV, which originates from the intestine, is associated initially with chylomicrons (Weisgraber et al., 1978). In rats, apoA-IV is found in HDL. By contrast,in humans, it exists in a lipid free form in fasting plasma. ApoB-48, a species of apoB that originates from the intestine, is a component of chylomicrons (Krishnaiah et al., 1980) and is not a precursor to apoB in LDL (Van t Hooft et al., 1982). While their roles are not known, it may be reasonably speculated that both apoA-IV and apoB-48 are involved in removal of chylomicron remnants by the liver. 

---