Experimental evidence has been found for associative phase separation in a mixture of a nonclouding hydrophobically modified poly(acry1amide) and sodium dodecyl sulfate. The phase separation is strongly dependent on the concentration of added Na2S04. The phase separation region in the presence of salt decreases with increasing temperature. Clearing transition temperatures from the two-phase to the one-phase region are reported. Fluorescence measurements using pyrene as the luminescence probe, l H NMR spectra, and viscosity measurements show that the interaction between polymer and surfactant takes place also when no phase separation occurs. In systems with 3% polymer concentration this interaction leads togel formation (but no phase separation) even in the absence of salt.

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The kinetic consequences of acetylcholinesterase peripheral site occupation by metal ions were examined using three substrates; acetylthiocholine, p-nitrophenylacetate, and 7-(dimethylcarbamoyloxy)-N-methylquinolinium iodide. Two classes of metal ion effects were noted: activation by a group including Mg2+, Ca2+, Mn2+, and Na+, and inactivation by a second group which to date includes Zn2+, Cd2+, Hg2+, Ni2+, Cu2+, and Pb2+. Activation is demonstrable only in solutions of low ionic strength whereas inactivation can be readily observed in solutions of both low and high ionic strength. Activation appears to be due to a combination of metal ion binding and ionic strength effects and involves binding to peripheral sites which are distinct from those which bind organic cationic activators such as gallamine, propidium, and 7-(dimethylcarbamoyloxy)-N-methylquinolinium. The principal activating effect is on the deacylation phase of the enzyme-substrate reaction. Inactivators effect a slow conversion of the enzyme to an unreactive form. The kinetics of inactivation are biphasic at low ionic strength but become essentially monophasic at high ionic strength. More than 80% of the enzyme activity can be recovered upon addition of EDTA provided the chelating agent is added immediately following completion of the inactivation process. Prolonged exposure to inactivators results in a progressive decrease in the amount of recoverable activity, Although peripheral ligand interactions may result in a variety of catalytic site conformations, the macroscopic properties can be accounted for in terms of three ligand-dependent states of the enzyme in which catalytic ability (actual or potential) is retained, and a fourth denatured state.

A study of the self-association of the anthracycline antibiotics adriamycin and daunomycin was undertaken in D,O and methanol using nmr at 400 MHz. From the concentration dependence of the ' H linewidths obtained on selectively deuterated daunomycin it was determined that daunomycin forms a dimer in aqueous solution. The concentration dependence of the chemical shift of the 4 methoxy group of adriamycin was fit to a dimer model in which only the non-protonated neutral species of adriamycin participated in the self-association process. The data were in agreement with the dimer model if a pK of 7.4 was used. The pH dependence of the self-association was fit to two ionizations, one with a pK of 8.2 and the other with a pK of 8.8. The latter pK was attributed to the ionization of the phenol based on the work of Eksborg. It was concluded that only the deprotonated amine of adriamycin took part in the dimerization process. The dimerization of adriamycin is characterized by a AS of approximately 3 cal deg-I M-' and a AH of -3.45 kcal M-'. At room temperature the association constant for the dimerization process was found to be 4.0 x lo5 M-'. These results were discussed in terms of earlier studies by Barthelemy-Clavey et al., Martin, and Chaires et al. Chem. 63, 1233Chem. 63, (1985. Faisant appel 5 la rmn a 400 MHz, on a entrepris une ttude sur l'auto-association des antibiotiques anthracyclines, adriamycine et daunomycine, en solutions dans le DzO et le methanol. En se basant sur la correlation qui existe entre la concentration et les largeurs des bandes *H, obtenue h l'aide d'une daunomycine deuttrie stlectivement, on a determine que la daunomycine forme un dimkre en solution aqueuse. La correlation qui existe entre la concentration et la deplacement chimique du groupement methoxyle en position 4 suggere l'existence d'un modele dans lequel seules les espkces neutres non-protonkes de I'adriamycine participeraient dans le processus d'auto-association. Si on utilise un pK de 7,4, les donnkes sont en accord avec le modtle dimere. La corrtlation qui existe entre le pH et I'auto-association correspond a deux ionisations, une avec un pK de 8,2 et une autre avec un pK de 8,8. En se basant sur le travail de Eksborg, on attribue ce dernier pK h I'ionisation du phenol. On en conclut que seule I'amine deprotonee de l'adriamycine prend part au processus de dimerisatjon. [Traduit par le journal] Introduction Adriamycin (doxorubicin, Adm) (I) and daunomycin (daunorubicin) are aminoglycoside anthracycline antibiotics that have been found to be effective antineoplastic agents in the treatment of promyelocytic leukemia and other lymphomas (1). Adrn differs from daunomycin in that it has a hydroxyl group on the C14 of the keto-alkyl side chain on the A ring. Since the discovery of Adm in the early 1950's a large amount of information has been accumulated on its mechanism of action both at the molecular and cellular level (2, 3). These anthracyclines are known to bind strongly to DNA in vitro although different modes of binding have b...

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