NEWS OF THE WEEK SCIENCE
BORON NEUTRON CAPTURE THERAPY Boron-rich porphyrin compound holds promise for treating cancer
B
IOLOGICAL EVALUATION OF
a compound designed to deliver therapeutic amounts of boron to tumor cells for radiation therapy is currently under way at Louisiana State University, Baton Rouge. The water-soluble fluorescent compound features an oligomeric phosphate diester (OPD) with two boron cages, one of which is covalently attached to a tetraphenylporphyrin. It was synthesized by LSU associate chemistry professor M. Graça H. Vicente, UCLA chemistry professor M. Frederick Hawthorne, and their coworkers [Chem. Commun., 2002,1784]. Boron neutron capture therapy (BNCT) entails the capture of neutrons by boron-10 nuclei that have been selectively delivered to tumor cells. Neutron capture leads to the formation of excited 4 He 2+ and 7Li3+ ions that result in cell death. "Targeting boron-rich OPDs to tumor cells has not been achieved as yet," Hawthorne tells C&EN. "However, porphyrin derivatives are known to be selectively taken up by tumor cells. Thus, in this paper, a tumor-cellselective porphyrin and a very simple OPD, which may translocate to the tumor cell nucleus, are combined in a simple molecule that hopefully will fulfill both requirements." B N C T is particularly attractive for the treatment of malignant brain tumors, Vicente notes. "However, there is a general perception that carboranylated porphyrins are too toxic for BNCT. Our work shows that a large number of these compounds are not toxic and are well tolerated in HTTP://PUBS.ACS.ORG/CEN
high concentrations in rodents. The new compound is the first covalently bound O P D - p o r phyrin conjugate to be synthesized. We are now evaluating its biological properties both in cells in culture and in animals." T h e researchers prepared the new compound in an eightstep synthesis that involved coupling two carboranyl alcohols with 2-chlorophen oxyphosphorus dichloride. T h e resulting carboranyl phosphate diester was Vicente converted into a carboxylic acid derivative and then linked to the fluorescent porphyrin. The fluorescent moiety allows the compound to be easily monitored in tissue. Boroncontaining malignant cells could thus be targeted and destroyed
even in the presence of normal, boron-free cells. "This important synthetic paper brings closer to reality the promise of BNCT for the treatment of cancer," comments Jonathan L. Sessler, chemistry professor at the University of Texas, Austin, who has developed a gadoHrrium-porphyrin drug for enhancing radiation-therapybased treatment of brain tumors (C&EN, Aug. 20,2001, page 36). "The present approach represents a quantum leap forward in that desirable molecular properties are combined with an elegant and efficient synthesis," he says. "However, the utility of this or any other earlystage 'attack' on the cancer problem can only be judged in the fullness of time once preclinical and clinical data start to become available." Hawthorne points out that there is immense scope for varying the structure of both the O P D and porphyrin components of the hybrid molecule. "The cell targeting and nuclear translocation properties of the hybrid species maybe optimized in future work," he says.—
AMPHIPHILIC Compound's expected affinity for lipidaqueous interfaces would favor boron uptake by tumor cells.
MICHAEL FREEMANTLE
ACCIDENT
Korean Adhesives Plant Blast Kills Three
T
hree people were killed and 12 were injured in an explosion on Sunday» Aug, 18, at a plant manufacturing carbon fiber composite adhesives in South Korea, The blast occurred at the Pyungtaek Works of Dongwoo Fine-Chem, a company 82% owned by Sumitomo Chemical. Production trials were under way at the plant as Sumitomo was in the process of transferring production of the adhesives, used by airplane manufacturers, to the site from a facility in Osaka» Japan, that was scheduled to be shut down. Other units at the complex were not damaged. The cause of the blast is unknown, a Dongwoo executive dispatched to Pyungtaek says» But he notes that epichlorohydrin and m-
aminophenol are two of the major raw materials for the adhesive. Sumitomo will continue to supply customers from its Osaka facilities. Dongwoo Fine-Chem is mostly a supplier of fine chemicals and materials to the Korean electronics industry. At the time of the accident, considerable construction activity was ongoing at Pyungtaek following a decision by Sumitomo to expand production of electronics materials in Korea (C&EN, April 15, page 18). Employing 312, Dongwoo was formed in 1991 as a joint venture between Korea's Oriental Chemical (50%), Sumitomo (40%), and itochu (10%). Oriental sold its stake to the other two during the financial crisis of 1998.—JEAN-FRANÇOIS TREMBLAY
C&EN
/ AUGUST
26, 2002
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