NEWS OF THE WEEK SYNTHETIC CHEMISTRY
BORON ATTACKS Electropositive element pressed into action as nucleophilic boryllithium
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N A BOLD MOVE FOR BORON
chemistry, scientists in Japan have synthesized, isolated, and characterized a boryllithium com pound for the first time {Science 2 0 0 6 , 314, 113). T h e novel b o ryl anion behaves efficiently as a base and as a nucleophile, opening "important synthetic pathways to boron-containing compounds," ac cording to the report. Even t h o u g h b o r o n sits im mediately to the left of carbon on the periodic table, the atom does not share its neighbor's reactive versatility. Boron compounds are almost always electrophilic, pre ferring to accept electrons rather
than donate them in a nucleophilic attack. "Although t h e r e have b e e n examples in which metal boryl species maybe considered nucleo philic, this is a clear-cut case of nucleophilic boron," says Todd B. Marder, a boron expert at Durham University in England. A hand ful of researchers have reported anionic organoboron alkali metal salts as reactive intermediates, but none were able to isolate or conclu sively characterize the anions. Theoretical predictions led Uni versity of Tokyo chemists Kyoko Nozaki, Makoto Yamashita, and Yasutomo Segawa to believe that a
CANCER RESEARCH
CIGARETTES' SMOKING GUN? Acrolein causes DNA mutations similar to those found in lung cancer
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CROLEIN, ONE OF THE 4 , 0 0 0
constituents of cigarette smoke, has been found un expectedly to cause D N A damage in the gene for the infamous tu mor-suppressor p53, which is often disrupted by cancer. In particular, the pattern of D N A mutations caused by acrolein mimics what is often found in human lung cancer samples (Prvc. Natl. Acad. Sa. USA, D O L 10.1073/pnas.060703H03). "If cigarette smoke is the weap on that causes lung cancer, then these mutations are fingerprints on the knife," says author Moonshong T a n g of N e w York Uni versity School of Medicine, in Tuxedo. Tang was also involved in identifying another cigarettesmoke component that can induce WWW.CEN-0NLINE.ORG
such mutations: a metabolite of a polycyclic hydrocarbon called benzo[tf}pyrene. Acrolein is pres ent in cigarette smoke in levels of up to 1,000 times greater t h a n benzofczlpyrene. Acrolein alkylates guanine resi dues in DNA, causing a pattern of D N A damage that is "remarkably similar to t h a t observed in the commonly mutated p53 gene iso lated from lung tumors in smok ers," comments Stephen S. Hecht of the University of Minnesota Cancer Center. "These results are tantalizing," H e c h t says. "But there is also a conundrum." Hecht points to an exhaustive review by the Interna tional Agency for Research on Can cer that did not find acrolein to be
diamino-substituted boryllith ium would be stable. To gener ate the species, the researchers reductively cleaved the B-Br bond in bulky 2-bromo diazaborole. They were able to verify t h a t they had indeed made a boryllithium species by X-ray crystallography and solution characterization. EMBOLDENED BORON T h i s type of boron anion Novel boryllithium shares the same number of va nucleophile attacks lence electrons as its popular car benzaldehyde. bon cousin, the N-heterocyclic carbene. The Tokyo team demon strated borylUthium's nucleophilic prowess in reactions with «-butyl chloride and benzaldehyde. "This is a very exciting time for boron chemistry," writes Marder in a commentary that accompanies the report. "The work opens the door to new pathways in boron diemistry that will have a substantial impact on both organic and inorganic syn thesis."-Β ΕΤΗ AN Y HALFORD
carcinogenic to laboratory animals. "It is possi ble that rodent metabolism of acrolein is dif ferent than in humans, but much more research is warranted," Hecht says. "Collec tively, Tang's data provide intrigu ing leads pertinent to a possible role of acrolein in smoking-induced cancer in spite of its apparently low carcinogenicity in laboratory animals." Gerd P. Pfeifer of Beckman Re search Institute suggests looking directly for acrolein-DNA adducts in lung biopsy samples from smokers. "The carcinogenicity of acrolein in animal models may need to be reevaluated," he says. There are 45 million smokers in the U.S. and 1.2 billion world wide. Careful analysis of all harm ful compounds in cigarettes could ultimately lead to regulations that would decrease the possibility of cancer development, H e c h t says.-SARAH EVERTS
CULPABLE Acrolein (red) alkylates guanine bases (black), causing DNA damage.
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