Ethoxzolamide and several derivatives (1-6) were synthesized and evaluated for carbonic anhydrase inhibition (CAI), solubility, pKa, distribution, and corneal permeability. The 6-hydroxy (5) and, particularly, the 6-chloro (6) analogues have the best combination of properties for penetrating the site of action and reducing intraocular pressure. Both 5 and 6 exhibited topical effectiveness in the normal rabbit, with 6 showing greater potency.
b S Supporting Information T his lab uses humulones (α-acids) and lupulones (β-acids) present in hops, a component of beer, to explore and explain several different chemical and mathematical concepts. The hop system is educationally engaging because it can be integrated into the curriculum at many different levels. In the nonmajors chemistry lab this experiment can be used to introduce the concept of an absolute method that does not require calibration versus a relative method that does. If a minor interfering species is ignored, the hop analysis can also be used at the general chemistry level to introduce the standard two-component analysis using high school algebra. At the chemistry major's analytical chemistry level the same lab can be used as a multicomponent analysis that includes an interfering species, and the mathematics behind the multicomponent analysis can be used as a bridge to the method of Gaussian elimination and matrix algebra to explain how systems of several equations and unknowns can be solved. At all levels a comparison of this method with the original, industry standard analysis method 1 can be used to illustrate a more "green" methodology in analytical methods development. This lab also can be used to expose students to units of specific absorptivity as well as the more often used unit of molar absorptivity. Finally, as a lab with a direct practical application to a real-world problem, a problem that will allow a student to interact with a brewer on a professional level, we predict that this exercise is one that the students will remember for years.Most analytical chemistry texts dealing with spectroscopy discuss the BeerÀLambert law,where A is the absorbance at a particular wavelength, ε is the absorption coefficient, l is the path length, and c is the concentration for a single absorbing species. In a two-component system the absorptions of the individual components add, soTo find the concentration of both components, the absorbance of the solution at two wavelengths must be obtained, and a system of two equations and two unknowns set up.Initially, the mixture of α-and β-acids present in a hop sample appears to be a simple two-component system that can be analyzed by standard techniques presented in most texts on UVÀvisible spectroscopic analysis. However, more careful analysis reveals that this system is a complex system containing at least two analytes and an additional interfering species.Hops, the inflorescence (cone) of the Humulus lupulus plant, contain both α-acids (humulones) and β-acids (lupulones), the major chemical components of which are shown in Figure 1. The quantity of α-and β-acids varies with the type of hop used, 2,3 how the hop was processed, 4 how it was stored, and how long it has ABSTRACT: A method is presented for the determination of α-and β-acids (humulones and lupulones) in a hops sample using a multicomponent UV spectroscopic analysis of a methanolic hop extract. When compared with standard methods, this lab can be considered "greener" because it uses smaller...
N-Methylacetazolamide was shown to be active topically in reducing intraocular pressure (IOP) to a small but statistically significant level in the normotensive rabbit eye. In vivo experiments with N-methylacetazolamide suggest that ocular metabolism to acetazolamide was responsible for the observed topical activity. Examination of initial rate kinetics of carbonic anhydrase catalyzed p-nitrophenyl acetate hydrolysis showed that N-methylacetazolamide was a competitive inhibitor, in contrast to noncompetitive inhibition seen with acetazolamide and other primary sulfonamide inhibitors. N-Substituted and unsubstituted 4-chlorobenzene- and 4-nitrobenzenesulfonamides were also synthesized, and their biochemical characteristics and in vivo ability to lower IOP when applied topically were determined. The primary sulfonamides were reversible noncompetitive inhibitors of carbonic anhydrase, with no effect on IOP after topical administration. 4-Nitrobenzene- and 4-chlorobenzenesulfonamides containing both N-hydroxy and N-methyl substituents were model irreversible inhibitors of carbonic anhydrase and exhibited a trend toward topical activity in reducing IOP in normotensive rabbit eyes. Therefore, this paper describes the synthesis and characterization of two types of carbonic anhydrase inhibitors; the N-methyl-substituted sulfonamides are reversible competitive inhibitors of carbonic anhydrase, while the N-hydroxy-N-methyl-substituted sulfonamides are irreversible inhibitors.
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