Dendritic polymer made by monomer self-condensation SnCI4. tetrabutylammonium bromide Self-condensation
CI
Sty renie monomer
Activated monomer Further selfcondensation and quenching with methanol
R = CI, OCH,
"The unique feature of the selfcondensing polymerization is that it is a 'living' vinyl polymerization in which the growing chains contain an ever-increasing number of branches and 'living' reactive sites," says Fréchet. He explains that the polymer is formed by a new mechanism that is neither polyaddition—as in classical vinyl polymerization—nor polycondensation, but rather a combination of both. The team demonstrated the method using the styrene derivative 3-(l-chloroethyl)-ethenylbenzene as the vinyl monomer. The 1-chloroethylbenzene part of this monomer is a latent initiator that can be activated by a mixture of stannic chloride [tin(IV) chloride, or SnCl4] and tetrabutylammonium bromide. Polymerization is carried out in dry dichloromethane under nitrogen and terminated by quenching with methanol. The resulting dendritic polymer has a molecular weight of over 100,000. "Fréchet's work represents a significant departure from conventional thinking regarding the synthesis of dendritic materials," says polymer scientist Joseph M. DeSimone of the University of North Carolina, Chapel Hill, and North Carolina State University. 8
AUGUST 28,1995 C&EN
Self-condensing vinyl polymerization is "a powerful synthetic methodology that utilizes a chain-growth polymerization mechanism," he adds. "As far as I know, all other synthetic approaches for dendritic materials have focused on chemistries normally associated with step-growth polymerizations. As such, the use of vinyl monomers and their derivatives for the synthesis of dendritic materials will undoubtedly lead to new materials, especially when extended to controlled free-radical polymerizations." Michael Freemantle
From ACS meeting
Cardiotonic steroid in humans is not ouabain A compound found in human plasma that has properties similar to the cardiotonic steroid ouabain is not, in fact, identical to ouabain. This finding by researchers at four institutions, presented at the American Chemical Society national meeting in Chicago last week, is likely to influence research on new cardiac drugs.
Ouabain (pronounced wa-bane), like the digitalis compounds digoxin and digitoxin from the purple foxglove plant, increases the intensity of heart muscle contraction. It is produced by Strophantus gratus, a poisonous plant used in folk medicine in East Africa. Cardiotonic steroids bind the plasma membrane enzymes that regulate intracellular sodium in mammalian cells. Because binding is so tight and specific, scientists speculated that an endogenous factor also must exist. Drug companies have been chasing this factor for the past 30 years, notes Columbia University chemistry professor Koji Nakanishi, whose group was part of the collaborative team. This is because digitalis compounds are toxic and their margin of safety is very narrow, explains Columbia senior research scientist Nina Berova. An endogenous analog likely would be less toxic. By 1976, scientists knew from physiological studies that an endogenous factor exists, says collaborator Garner T. Haupert Jr., a nephrologist at Massachusetts General Hospital, Harvard Medical School, Charlestown, Mass. But the first report of a structure came only in 1991, when scientists isolated from human plasma a substance dubbed "ouabainlike compound" (OLC). OLC's discoverers found no difference between OLC and ouabain and concluded the two were identical. That conclusion has been proven wrong by the Columbia-Harvard team, using 400 ng of a 1-pg gift of OLC from James H. Ludens of Upjohn Laboratories, Kalamazoo, Mich., who helped isolate OLC. The evidence comes from a technique called exciton-coupled circular dichroism (CD). The Columbia group converted hydroxyls to highly UV-absorbing and fluorescent chromophores and then obtained the exciton-coupled CD spectra of the derivatives. "The results were exciting," says Berova. "We got the first direct evidence that OLC and ouabain are not identical": Coinjection of the OLC and ouabain derivatives gave two distinct chromatographic peaks, and their exciton-coupled CD spectra were different. The Columbia group previously used the CD strategy in work on an endogenous factor called HIF. Their Harvard collaborators had isolated 3 pg of HIF from bovine hypothalamus over a 10-year period. Chemical studies
employer use of ACS employment services, production of career options videotapes, compilation of a sourcebook to illustrate how disabled chemists can work productively in science environments, and conferences to train local sections how to set up mentoring programs for women and minority members who have recently joined ACS. In addition, a prototype of ACS's new on-line job data bank was demonstrated for member input at the Internet Corral, an assembly of some 20 computers in the meeting exposition area. Slated to start up Jan. 1, the data bank lists job postings for candidates and recruiters and will be available on the World Wide Web. Among a host of other job and career From ACS meeting services at the meeting, the society's long-standing National Employment Clearing House (NECH) set a record Job and career assistance efforts domi- for up to two years for a member who is for job candidates served—about 1,590 nated new programs approved by Amer- unemployed and seeking full-time pro- at press time. These candidates held ican Chemical Society governing bodies fessional employment. This provision more than 1,700 interviews with 120 or at ACS's 210th national meeting in Chi- supersedes the current board regulation so employers, who listed about 425 cago. For instance, the ACS Council that defers, but does not waive, dues pay- available positions. Unfortunately, this adopted two proposals to provide dues ment for up to three years. The second high level of activity at NECH confirms relief to ACS members who become un- measure provides a 50% dues discount the continuing poor job market for employed or who take a break from their for up to three years for members who chemical professionals. careers for family reasons. And the ACS suspend full-time employment because The meeting also offered the usual Board approved five new career services of long-term family-care obligations— huge variety of technical, governance, programs that will begin next year. such as raising a family or caring for eld- and social activities. Highlights ranged from ACS President Brian M. Rushton's The council proposals will amend ACS erly parents. bylaws, upon confirmation by the board, The board approved the new career well-attended presidential event, a minito provide moderate assistance to mem- assistance programs as part of its plan- exhibition called "Industry's Creative Inbers facing financial difficulties who ning for the 1996 budget. Approved ventions: From the Lab to Your Home," might otherwise resign, enhancing the were a local section program to provide to a crowded performance of the Dow society's efforts to retain members. One of employment and career assistance, a pi- Chemical-sponsored "Chem-TV" stage the programs waives membership dues lot telemarketing program to increase show at the National Chemistry Week Phoenix Awards ceremony. The meeting drew about 10,000 attendees—about 12,300 counting exhibitors and visitors— who presented more than 4,700 papers. Among other ACS governance actions, the board approved funding in next year's budget for three new public outreach programs. It also approved establishment next year of Project Instrumentshare, which is designed to facilitate transfer of donated equipment and instruments from U.S. agencies and companies to chemical scientists and engineers at needy domestic and foreign institutions. Besides adopting the two petitions on dues relief, the council set members' advance registration fees for next year's two national meetings at $200, up $10 from this year. And it approved establishment of a probationary Members of ACS Chicago Section, led by chairman Cherlyn Bradley (center), blow outDivision of Chemical Toxicology. Ernest Carpenter candles on cake marking section's 100th birthday, celebrated at presidential event. by another collaborator, Adrienne A. Tymiak, a chemist at Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, N.J., indicated HIF might be structurally identical to ouabain. But Haupert found HIF was more active than ouabain and less toxic. The researchers concluded that ouabain and HIF must have subtle structural differences not revealed by mass spectrometry and chromatography. The tiny amount of pure HIF available for further structural studies— about 300 ng—required an innovative approach. So the Columbia group turned to exciton-coupled CD. Results
were astonishing: two peaks on coinjection and different exciton-coupled CD spectra, proving unequivocally that HIF and ouabain are different. It would have been impossible to get such data by nuclear magnetic resonance spectroscopy or X-ray, Berova tells C&EN. The team then compared OLC with HIF and concluded the compounds probably are identical [Biochemistry, 34, 9893 (1995)]. Their structures are still unresolved, but Nakanishi and Berova say they are prepared to complete the structural study with the 10 pg of HIF that may be available. Maureen Rouhi
ACS approves new job, career aid programs
AUGUST 28, 1995 C&EN
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