The earliest correlations

The next correlation was found in Scotland where Crum Brown and Fraser (1869) made a major discovery. They showed that several alkaloids, when quaternized, lost their characteristic pharmacological properties (many of them spasmogenic or convulsant) and acquired the muscle-relaxing powers of tubocurarine (2.6) (itself a quaternary amine), whose site of action had been shown to lie at the jimction between nerve and voluntary muscle, a few years earlier, by Claude Bernard (1856). Strychnine, bruceine, thebaine, codeine, morphine, nicotine, atropine, and coniine were quaternized into curarimimetic substances, by reaction with methyl iodide. The Scottish authors wrote There can be no reasonable doubt that a relation exists between the physiological action of a substance and its 

Meanwhile attention was drawn to the overriding importance of a physical property when, at the turn of the present century, Overton and Meyer independently put forward a Lipoid Theory of Cellular Depression (Meyer, 1899 Overton, 1901). This stated that chemically inert substances, of widely different molecular structures, exert depressant properties on those cells (particularly those of the central nervous system) that are rich in lipids and that the higher the partition coefficient (between any lipid solvent and water) the greater the depressant action. This statement requires only insertion of the words, up to the point where hydrophilic properties are almost extinguished after partition coefficient to outline the present day viewpoint. It is now appreciated that the relationship between lipophilicity and depression of nerve functioning is a parabolic one, because substances that are entirely lipophilic become trapped in other lipids and do not enter the cell (Hansch et al., 1968). Table 2.1 offers 

CORRELATION OF LIPID/WATER PARTITION COEFFICIENTS WITH BIOLOGICAL DEPRESSION (SUPPRESSION OF MOTILITY OF TADPOLES) 

Substance Partition coefficient olive oHjwater Minimal immobilizing concentration, mol/1 (water) 

Depressants may be hydrocarbons, halogenated hydrocarbons, alcohols, ethers, ketones, weak acids (like the barbiturates), weak bases, or simple sulphones. They are the selectively toxic agents used in medicine as hypnotics and general anaesthetics. This is the only kind of biological activity in which structure simply does hot matter (there is much more about this in Chapter 15). See Section 3.2 for the general function of partition effects in securing selective distribution of drugs. 

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Establishing correlations between the stability of complexes and factors related to the characteristics of the metal ion and ligands involved is not a new endeavor. One of the earliest correlations established showed that for many types of ligands, the stability of the complexes that they form with +2 ions of first-row transition metals varies in the order... 

For some time coordination chemists were aware of certain trends in the stability of metal complexes. One of the earliest correlations was the Irving-V/illiams series of stability For a given ligand, the stability of complexes with dipositive metal ions follows the order Ba2+ < Sr2+ < Ca2+ < Mg2+ < Mn2+ < Fez+ < Co2+ < Ni2+ < Cu"+ > Zn +. This order arises in part from a decrease in size across the series and in... 

Many useful correlations have been published to determine the friction factor for fully developed turbulent flow of Newtonian fluids in smooth pipes. One of the earliest correlations was given by Blasius (8) as follows ... 

Algebraic correlations are used extensively to represent turbulent convective heat transfer data. One of the earliest correlations used for fully developed turbulent flow heat transfer is the Dittus-Boelter correlation ... 

One of the earliest correlations of nucleophilicity with basicity was provided by Smith for the reaction of carboxylate ions (Y = RCOJ or ArCOj) with chloroacetate ion. 

Some of the earliest correlations between nucleophilicity and reactivity focused solely on the pKn of the conjugate acid of the nucleophile. If one keeps the electronic and steric properties of a series of nucleophiles similar, and uses the same solvent for the analyses, reactivity does nicely correlate with the basicity of the nucleophile Kt, see Chapter 5). An LFER as defined in Eq. 8.48 can be used to correlate the data. This structure-function relationship is called a Brensted relationship. 

Figures 9-21B and -21C are the earliest generalized pressure drop correlations (GPDC) proposed and have been used for many industrial plant design. Progressively, Figures 9-21E-H are more recent correlations. These charts will be discussed in a later section.

The IRAS galaxies provided some of the earliest evidence from redshift surveys, and from source counts as a function of observed flux, that the spiral galaxy population has undergone evolution (ORS see Fig. 12.2). This result is analogous to similar evidence from source counts of radio galaxies and quasars, as well as quasar redshifts, and a correlation that has been observed between radio and infrared luminosity suggests that the evolution could be similar in both cases. Typical simple models for such evolution include luminosity evolution according to... 

The earliest of the magnetization transfer experiments is the spin population inversion (SPI) experiment [27]. By selectively irradiating and inverting one of the 13C satellites of a proton resonance, the recorded proton spectrum is correspondingly perturbed and enhanced. Experiments of this type have been successfully utilized to solve complex structural assignments. They also form the basis for 2D-heteronuclear chemical shift correlation experiments that are discussed in more detail later in this chapter. 

Hyphenated heteronuclear shift correlation methods Many of the experiments described thus far can be used as building blocks to create more sophisticated pulse sequences. The earliest variants of hyphenated NMR experiments, such as HC-RELAY, were heteronuclear detected [56]. More recent hyphenated heteronuclear shift correlation methods are based on proton detection and include... 

Proof of Constitution.—Since the crystalline a- and 8-forms of 3,4,6-trimethyl-D-glucose, isolated by Sundberg and coworkers,28 were each obtained by hydrolysis of methyl 3,4,6-trimethyl-/3-D-glucopyrano-side,82,154 the proof of the constitution of this glucoside obviously played an important part in the characterization of the trimethylglucose itself. Unfortunately, there is no such crystalline reference compound to correlate the earliest samples of sirupy 3,4,6-trimethyl-D-glucose157,168 with the crystalline specimens isolated by Sundberg and coworkers. 

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