Physical chemistry in pharmaceutical research - Journal of Chemical

Considers the role of physical chemistry in pharmaceutical research by examining the determination of the structure of the antibiotic chloromycetin...
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DECEMBER, 1953

PHYSICAL CHEMISTRY IN PHARMACEUTICAL RESEARCH1 1. M. VANDENBELT Parke Davis and Company,Detroit, Michigan

THEphysical chemistry of the modern pharmaceutical laboratory is t o some extent a complicated analytical chemistry. Recent developments in the field range from seemingly simple 'techniques, using old and familiar materials, to relatively expensive and elaborate arrangements, employing the very latest developments in the fields of optics and electronics. So varied and valuable have these techniques become during the last decade that sizable laboratories usually have a group charged principally with the responsibilities for these operations. It usually requires several months for an operator to become thoroughly familiar u-ith a new technique. It may take as many years to acquire an adequate hackground and experience in the interpretation of data. I t is by combination of these manipulative skills with the specialized experience that the finest yield in investigative return is obtained. A specific example of the contribution that a physical Presented at the 49th meeting of the Michigan College Chemistry Teaehcrs Association, May 9, 1952.

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Curve 1: A-65 Curve 2: p-nitrotoluene O,N

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Curve 2: p-toluidine (ord. X %) Curve 3: A-65 red. in HCl Curve 4 : P-toluidine in HCI (ord.

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method may make is shown in the determination of the structure of the antibiotic A-65, Cbloromycetin. Figure 1 shows the ultraviolet absorption spectrum of the antibiotic. From experience with many types of spectra, it would seem that the characteristics resemble most closely those of a nitrohenzene derivative. For comparison, the curve of p-nitrotoluene is given in the figure. The similarity in hand shapes and positions of the two curves indicates that the chrornophores are closely related. To test the nitrohenzene hypothesis, a simple chemical reduction mas performed on the antibiotic. This should give the amino derivative similar in chromophoric properties to p-toluidine. The solid curves in Figure 2 show a convincing similarity. .Is a further check, both reduction product and p-toluidine were examined in strongly acid solution. Agaiu there is a striking agreement, indicating that indeed the antibiotic contains a p-nitrobenzyl group. A sizable portion of the structure of the new compound mas thus e~tablishedin a few honrs.