Summary
The circular dichroism spectra of 12 benzodiazepine derivatives studied in presence of human serum albumin are presented. Nearly all substances give biphasic extrinsic Cotton effects. At the CD maxima the molar ellipticities and the anisotropy factors are calculated. The influence of the chemical structure of the benzodiazepines on the induced Cotton effect is discussed. There is a linear correlation between the anisotropy factors and the logarithms of the partition coefficients of the substances. It is suggested that the phenyl ring of the benzodiazepine molecule is one of the essential groups for the binding of these substances to human serum albumin.
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Bell, S. T., Childress, S. J.: A rearrangement of 5-aryl-1,3-dihydro-2H-1,4-benzodiazepine-2-one-4-oxides. J. org. Chem. 27, 1691–1695 (1962).
Chignell, C. F.: Optical studies of drug-protein complexes. 2. Interaction of phenyl-butazon and its analogues with human serum albumin. Molec. Pharmacol. 5, 244–252 (1969a).
Chignell, C. F.: Optical studies of drug-protein complexes. 3. Interaction of flufenamic acid and other N-arylanthranilates with serum albumin. Molec. Pharmacol. 5, 455–462 (1969b).
Franke, R.: Die hydrophobe Wechselwirkung von polycyclischen aromatischen Kohlenwasserstoffen mit Humanserumalbumin. Biochim. biophys. Acta (Amst.) 160, 378–395 (1968).
Hansch, C., Kiehs, K., Lawrence, G. L.: The role of substituents in the hydrophobic bonding of phenols by serum and mitochondrial proteins. J. Amer. chem. Soc. 87, 5770–5773 (1965).
Krieglstein, J., Meiler, W., Staab, J.: Hydrophobic and ionic interactions of phenothiazine derivatives with bovine serum albumin. Biochem. Pharmacol. 21, 985–997 (1972).
Kuhn, W.: The physical significance of optical rotatory power. Trans. Faraday Soc. 26, 293–308 (1930).
Legrand, M., Viennet, R.: Dichroisme circulaire optique de la sérumalbumine humaine, en relation avec la dénaturation par l'urée et la rupture des ponts S-S. C. R. Acad. Sci. (Paris) 259, 4277–4280 (1964).
Müller, W., Wollert, U.: The interaction of some benzodiazepine derivatives with human serum albumin, circular dichroism studies. Naunyn-Schmiedeberg's Arch. Pharmacol. 277, R 49 (1973).
Murrell, J. N.: The theory of the electronic spectra of organic molecules. London: 1963. Methuen & Co. Ltd.
Perrin, J. H., Hart, P. A.: Small molecule-macromolecule interactions as studied by optical rotatory dispersion—circular dichroism. J. Pharm. Sci. 59, 431–448 (1970).
Schellman, J. A.: Symmetry rules for optical rotation. Acc. Chem. Res. 1, 144–151 (1968).
Sjöholm, I., Sjödin, T.: Binding of drugs to human serum albumin. 1. Circular dichroism studies on the binding of some analgesics, sedatives and antidepressive agents. Biochem. Pharmacol. 21, 3041–3052 (1972).
Uskoković, M., Jacobelli, J., Wenner, W.: 3H-1,4-benzodiazepine-2,5 (1H, 4H)-dione and related compounds. J. org. Chem. 27, 3606–3608 (1962).
Vandenbelt, J. M., Hansch, C., Church, C.: Binding of apolar molecules by serum albumin. J. med. Chem. 15, 787–789 (1972).
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Müller, W., Wollert, U. Interactions of benzodiazepines with human serum albumin. Naunyn-Schmiedeberg's Arch. Pharmacol. 278, 301–312 (1973). https://doi.org/10.1007/BF00500291
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DOI: https://doi.org/10.1007/BF00500291