Document MJm56EmoJwzNkEMjjb4ZEajX9

1Le a d A l k 7 3 Report, 19oo-19bl During the past year, two papers tokening on the orpanolead ions have been noted that may have some application in biological work. These are the papers of Snyder and Henderson on the determination of lead in air and in antiknock blends by the dithizon reaction (Analytical Chemistry JHjy 117^"^^, km., l^tlj * We have just submitted fox* publication a brief communication on the solubility of tetraethy H e a d (TELj in water. About J.T'y mgm. of TEL dissolves in a liter of water at 0 to q.j C ,,, a rather low solubility. by way of comparison, if may be noted that TEL is only ten times more soluble than metallic mercury (estimate of Walter Hughes, 1997) Our values will be the first to be published; the solubilities privately reported in the literature of Ethyl Corporation are to to tJ times as .great. The measured aqueous solubility emphasizes the probability that TEL will associate with lipid materials in the body. Consideration of Hildebrand's solubility parameters sug. eats that some sterol3 may closely resemble TEL in solubility, but other factors as we*! as solubility are doubtless important in determining thdistribution of TEL among tissues and cellular compone nts. If TEL is to be eliminated as 3uch from the tod... it will probably be dissolved in lipid, e.g., via the intestinal tract in mineral oil. / / t/ It' TEL is not eliminated as such from the tody, it is decomposed. The first decomposition product *e have identified ts being formed _in vivo is the triethyllead ion. This is formed exclusively in the liver, presumably in the microsumes of the liver cells, according to Gremer (1999) Perhaps the diethyllead ion is also formed, but of this there is little evidence as yet. The organolead ions must be formed as complexes with chemical groups presently un 1den tified . bec5u.se the organolead ions ire capable of combining more firmly then TEL with bodily constituents, inc because they ere formed from TEL to a rather large extent, and because they persist in the body for days after their formation, and because, although formed in one organ, they are transported throughout the body and thus affect other organs, these ions warrant our attention. because the organolead ions are presumably brou.-ht into existence as complexes in the calls, and because they probably exist in the body in combinations somewhat resembling those of the inorganic lead ions, and bcus they may be expected to exert their influences on bo'MIj functions through their combinations with various chemical groups, it is important to determine the affinities of these i^ns for the various chemically functional groups with which they may come into contact in the body. In other words, the stability constants of the organolead ions with various ligands are of 0003404 Jw w * ^ vc r; vj 3 concern in discovering what happens to TEL in the body. The stability cuiisto.nts of such complexes ere far from being trie sola determinants of cne fete of the organ d e e d ions in ti-.e body, as corj3l';or*tiona of solubility, molecular shape an t* other properties ill <!\, once sug est. Study of the complexes may, nevertheless, be important in suggesting likely alternatives concerning the sites of action cf the organolend lour in cellular metabolism, the mechanisms of transport of trie or ge.no'lead ions into and our of cello and in the blood stream, the kinds of reagents that ma y be useful in detecting and hr extracting the organoiesd ions from tissues, and the ligands that may decrease the toxicity of the orran of ands. One group of complexes of the organ dead Ions with which we have worked is the group of dit'nizone complexes, as our publications have recorded. Tne analytical work v9 have hone with the dithisenates has been based upon spectrophotometry. fro::; this experience and from observing that a number of the Comdexes of inorganic lead have been the subject cf spectrophotometry over the past thirty years we began fcur work on the organolead complexes with spectrophetoometric observat .otis , Spectra of a number of organolea complexes were octal ned. Gradually, it became evident that these spectra, obtained on the Beckman DK instrument, were unreliable. We changed to the Cary instrument, in the- Chemistry Department. Although reliability was increased, the relative inaccessibility cf the instrument and various problems of technic that had at first seemed -u- Kj, ou e v t t U unimportant, together with an increasing realization of sosae, of the limitations of the methodology (confirmed in ths literature eg. on page pQ of Reasotti and Rossotti's b 0 Q L i 19 bl) lod us to turn from spectrophotometry to the potentiomtrie measurement of the stability constants in complex formation* ae a way of approach. The potentiometric measurements shoe clearly the existence of complexes of the organ de ad ions in aqueous solutions at body temperature. In general, the diethyllead ion. forms stronger combinations with Uganda than does the trie thy H e a d ion; Of- the three ions, the inorganic lead ion forms, so far as we have determined:,, the strongest, most stable complexes. The strongest- complex we have observed is that of EDTA (Verseue, ethyienediamine tetraacetic acid) with inorganic lead. ECT1 also complexes sith the diethyllead loo, contrary to published report, but a complex of the triethyllead ion !th EDTA is barely detectable by the technic e have usee. These observations not only suggest why EDTA may fail to counteract tbs toxicity of trfcethyllead (as reported for alicea of brain, by Cremer) but indicate that the analogy bat ween the orgsnolead ions and inorganic lead may be- pushed too far. In SDTA, the coraplexing groups are the cerboxyl groups and the nitrogen atoms. We have examiner the completing strength of these groups in other molecules, e.g., acetate, benzoate, amlnoaoetato. And we have examined molecules containing other types of groups, e.g., thiols, phenolic u. osevens /*/ /- hydroxyl, pnoaphetes singly and In various combinations. Th thlolt are, next to EDTA, the strongest complexera weha Vi? nottc*c It- c-fiv l ta-ma th..ou f BAL, *e encountered impurities that seriously iatoi-rered *i<;h our measurements. At least one ef there iiapuritiee, trithiopropane, as recently round \J. to;. Ph-ari,;. r .. 19bo, to to* reapor-iSi'Dl* for uscue toxicity la B A L - With the analytical division, * are eurronclv c n t y to c if the methods- cf g * l chromatcgr& phy eon b* used it determining tue impurities it BAL, as an a it m preparing Ba L i"or our measurement..< V.o have iiuupli fed trie thy H e a d chloride sun other ionic orgu/joieaa ooiapcu&as thet sc have- synthesized t*. others In the iaocratcry. A v. v wc ore continuing oo ex pi ore the chemistry cf ihe c cr;pXee.... of m x organol esd ions and c? inorganic be he lor t:v rese&rch in cancer is corst 1ruing j & paper on this ess published in Experimental Cell Research Z'J ; 0^9" bv (19o'J; v K 0003407 K S 0003409