Cage compound shows tricyclic structure . . .
Phosphorus caged in new compound
CHICAGO A trivalent phosphorus has been trapped in a pentacoordinate intermediate state as it undergoes nucleophilic attack by an amine nitrogen in the phosphorus-nitrogen cage compound, [H + P(OCH 2 CH 2 )3N]BF 4 -. This result has been the serendipitous consequence of efforts to study the nitrogen phosphorus coordination chemistry of a cage compound, P(OCH2CH2)3N, in which phosphorus and nitrogen are linked by three separate —OCH2CH2— bridges. The bridging appears to allow the nitrogen lone electron pair to confer unusually intense basic properties on the phosphorus in the cation. Phosphorus-31 nuclear magnetic resonance spectra of the new cage cation salt at room temperature show a sharp doublet, indicating a phosphorus-hydrogen bond, even in the presence of the strong base, ethoxide anion, in acetonitrile solvent. The unusually low phosphorus-hydrogen coupling constant and high 3 1 P chemical shift of the cation are consistent with a trigonal bipyramidal geometry around phosphorus that represents the trapped phosphorus pentacoordinate intermediate, according to Dr. John G. Verkade of Iowa State University and graduate student Dean Milbrath, who presented the results in a poster session held by the Division of Inorganic Chemistry. When the possible effects of bridging are eliminated by mixing trimethylphosphite, triethylamine, and a proton source, no evidence of a phosphorus-hydrogen bond appears in the 3 1 P NMR spectrum, Verkade says. The Iowa scientists prepare their cage compound by refluxing trisdimethylamino phosphine with triethanolamine in benzene. From proton NMR spectra, Verkade estimates that about 12% of the product mixture (based on ethanolamine) is the cage compound, and the remainder consists of unvolatilized dimethylamine and unidentified polymer. Because the cage compound readily polymerizes upon isolation, chemical studies are performed on the filtered product solution, he notes. These studies show not only some expected results but some rather anomalous observations, indicating the propensity of the cage compound toward protonation, Verkade says. For example, the cage compound is protonated at room temperature by hydrochloric acid, whereas a similar cage in which a carbon replaces a nitrogen, P(OCH2)3CR, is not. When P(OCH 2 )3CR is treated with a source of ethyl carbonium ion, E t a O + B F ^ , an ethyl-phosphorus bond forms; how20
C&EN Sept. 8, 1975
notes. To get a representative effect, the samples should be placed deep in muscle tissue and preferably in direct contact with bone or tooth. Fortunately, not all metals have H—P N proved to be carcinogenic, Furst admits. Of those that he and others have tested, aluminum, copper, gold, iron, lead, and silver are among those that are benign, although they dissolve to varying degrees in body fluids. . . . rather than bicyclic Cadmium is one of the worst offenders. Furst notes that cadmium powder suspended in trioctanoin—a triglyceride of octanoic acid that is biologically inert—induces tumors in rats at the H—P-0 N site of injection within four months. Metastasis quickly spreads to the lungs causing death about two months later. Nickel powder and every nickel compound Furst has tested to date cause tumors in animals. Nickel itself is extremely soluble in biological fluids, dissolving at body temperature within ever, the cage compound again is pro- hours. In this connection he foresees a tonated. Moreover, no phosphate tries- potential hazard from the increasing use ter product has been identified in at- of nickel alloys in dental fillings and tempts to oxidize the phosphorus-nitro- prostheses. What isn't known is the exgen cage compound with dinitrogen tent to which the nickel in each alloy is tetroxide, ozone, and other oxidants. subject to release into the surrounding tissue. Again, the protonated form is observed. This chemical evidence, combined As an initial step in a screening prowith 3 1 P NMR observations, leads Ver- gram, the alloy should be incubated in kade to believe that the new cage com- reconstituted blood plasma at body pound has a tricyclic structure in temperature for up to five days. If which the —OCH 2 CH 2 — bridges are nickel shows up on atomic absorption arrayed like paddlewheels about a P-N analysis of the plasma, then the alloy axis. Using x-ray crystallography, the should be tested rigorously in animals molecular structure of the new cation for carcinogenicity. was confirmed in collaboration with Hexavalent chromium is another eleDr. Jon Clardy and graduate student ment whose toxicity is well docuJames Springer, also at Iowa State. mented on the basis of experimental The P-N distance, 1.99 A, is nearly the and epidemiological evidence, Furst sum of the covalent radii of phosphorus notes. For example, 3 mg of lead chroand nitrogen, Verkade says. mate injected intramuscularly into rats The next step, says the Iowa chem- in each case leads to development of ist, is to study the coordinating proper- cancer at the site of injection. In conties of the nitrogen atom in the cage trast, lead powder similarly tested compound by protonation studies in doesn't cause tumors. The fact that strong acid media. • both nickel and chromium occur in the makeup of prosthetic devices is additional cause for concern, he maintains. So far there is no way of predicting which metals will induce cancers and which will not. Similarity in atomic structure, for example, doesn't appear Body tissues and fluids are much more to be a criterion. aggressive in their attack on metals There may be some relationship bethan is generally recognized. A direct tween the microcrystalline structure of outcome is that the solubilized metals an alloy and its tumor-generating cacan present a biohazard because many pability, Furst theorizes, although he are carcinogenic, Dr. Arthur Furst, di- hastens to add that such a likelihood rector of the University of San Francis- has yet to be explored. But if this is co's Institute of Chemical Biology, the case, it might be possible to develop points out. alloys containing potentially carcinoWhen he addressed a group of ortho- genic metals with modified crystalline pedic surgeons at a private seminar in structures that would ensure that they West Germany last month, Furst urged are biologically benign. "So far, this that all metals and their alloys be has been a fairly unexplored field and carefully screened for their potential much work should be goii^g on," he tumorigenic activity before prosthetic says. He hopes that the limited results devices or dental fillings made from to date will provide the impetus for them are used. In such a screening pro- evaluating prosthetic devices used gram, it isn't enough merely to expose today and for research toward develan experimental animal to subcuta- oping new materials that will have no • neous or intraperitoneal implants, he potential biohazard.
Screening of metal implants urged
