Ring polyphosphate

Although reasonably stable at room temperature under neutral conditions, tri- and tetrametaphosphate ions readily hydrolyze in strongly acidic or basic solution via polyphosphate intermediates. The hydrolysis is first-order under constant pH. Small cycHc phosphates, in particular trimetaphosphate, undergo hydrolysis via nucleophilic attack by hydroxide ion to yield tripolyphosphate. The ring strain also makes these stmctures susceptible to nucleophilic ring opening by other nucleophiles. 

Guo et al. investigated the ring closure of N-(4-fluoro-3-chlorophenyl)-aminomethylenemalonate (757, R = Cl, R1 = F) under acidic conditions (see Table VI). A mixture of 5- and 7-chloro-6-fluoroquinoline-3-carboxyl-ates (758 and 759, R = Cl, R1 = F) was obtained, in 10-55% yields. The best yield was achieved in polyphosphate (86MI13 87MI7). 

The ring closure of (V-[4-ethyl-3-(2-chlorophenoxy)methylphenyl]ami-nomethylenemalonate (757, R = 2-ClPhOCH2, R1 = Et) in polyphosphate (prepared from phosphorus pentoxide and ethanol in xylene at 100°C) at 150°C for 30 min afforded quinoline-3-carboxylate (759, R = 2-ClPhOCH2, R1 = Et) in 74% yield (79EGP136742). 

Okumura et al. studied the ring closure of N-ethyl-A/-(3,4-methylenedi-oxyphenyI)aminomethylenemaIonate (286) in polyphosphoric acid and polyphosphate, which gave the linear tricycle (755). The cyclization gave a better yield in polyphosphate than in polyphosphoric acid. Compound 755 was obtained in 78% yield in polyphosphate at U0-120°C for 1 hr, but in only 64% yield in polyphosphoric acid at 120-130°C for 30 min [72JCS(P1)173],... 

During the heating of /V-(2-carboxy-3-thienyl)aminomethylenemalo-nates (886, R = H, Ph) in boiling diphenyl ether (88EUP269295) or in polyphosphate [78JCR(M)4701, 78JCR(S)393], the ring closure was accompanied by decarboxylation to thieno[3,2-fe]pyridines (885, R = H, 2-Ph). 

Perhaps the formation of trimetaphosphate and small quantities of tetrametaphosphate from dissolved polyphosphates, which can amount to 70% in presence of Mg++ ions, is an indication of the form in which the anion chains are present in the solution. In any case this formation of trimetaphosphates is not, contrary to what was proposed initially (293, 326), an argument for the assumption that trimetaphosphate rings constitute a structural unit in the polyphosphates. Thus in solutions of Maddrell s salt, the anions of which are known to be linear chains from crystal structure determination (78) (see Section IV,E,2), up to 50% yields of trimeta-... 

The /3-form of the arsenatophosphate and /3-KAs03 contain trimeric anionic rings. This follows from the isomorphism with the low temperature form of K3(P309), which is formed when KH2P04 is treated with a mixture of acetic acid and acetic anhydride 121). It may also be concluded from the observation that in the hydrolysate of /3-arsenatophosphate it is possible to detect, in addition to monoarsenate and a little trimetaphosphate, only mono- and diphosphate, but no tri- or higher polyphosphate 121). The /3-forms of arsenatophosphates contain anions of the types ... 

Bischler -Napieralski ring closure of 5 (R = CHO) with phosphorus oxychloride6,8 9 and of 5 (R = COCH3) with phosphorus oxychloride6, 8 or polyphosphate ester10 gave 8 (R = H and R = CH3, respectively). Reduction of 8 (R = H) with lithium aluminum hydride... 

Enzymatic activity, however, is not merely associated with covalent structures, but chiefly with tertiary structure which is still more difficult to determine. The crucial role of tertiary structure is proved by the fact that denaturation brings about inactivation. Even with proteins which may be reversibly denatured, such as chymotrypsin and trypsin, activity is lost as long as denaturation persists. Ribonuclease appeared for a while to be an exception, since it was still active in 8 M urea. But it was shown later that phosphate ions, at a concentration as low as 0.003 M, and polyphosphates induced in urea-denatured ribonuclease spectral changes usually associated with refolding (164). It could then be assumed that ribonucleic acid, the actual substrate, was also able to refold the denatured form and prevent inactivation in this way. In other words, even in ribonuclease, the active center is probably not built by adjacent residues in a tail or a ring, but by some residues correctly located in space by the superimposed... 

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