Chemicals are tested for mosquito repellency - C&EN Global

Eng. News , 1969, 47 (39), pp 52–53 ... repellency over the years, N,N-diethyl-m-toluamide (DEET), which dates back to World War II, though far from...
2 downloads 0 Views 455KB Size
Chemicals are tested for mosquito repellency MEDICINAL

iy'/'"?'H \

Of the many thousands of compounds that have been screened for their mosquito repellency over the years, N,Ndietiiyl-m-toluamide ( D E E T ) , which dates back to World War II, though far from being ideal, is still the best that's available. But the emergence of mosquito strains that have somehow adapted themselves to insecticides, coupled with the appearance of drugresistant malaria parasites, is a matter of growing concern, particularly in view of our continuing involvement in malaria-ridden southeast Asia. A program now under way at Stanford Research Institute in Menlo Park, Calif., is geared to learning more about what are the structural features of molecules that enhance mosquito repellency. The ultimate goal is to come up with a compound that is more potent than D E E T and that lacks that chemical's practical limitations. A significant finding that should aid in the search, observes Dr. W. A. Skinner, executive director of S Ill's life sciences division, who heads the U.S. Army- and SRI-sponsored project, is that within a given structural series of compounds there's a boiling point range that indicates which compounds give maximum protection against mosquitoes. He and coworker Dr. Howard Johnson made the discovery when they plotted protection time of homologs against their boiling points. Mosquito repellency increases, peaks, and then declines with advancing boiling points. While the peak point varies from one series to the next, the finding rules out needless synthesis and screening of chemicals once that point has been past, Dr. Skinner notes. To pinpoint structural features that contribute to mosquito repellency, the SRI chemists converted into Wiswesser line notation the formulas of the nearly 20,000 compounds in the U.S. Department of Agriculture's Handbooks 69 and 340. These books list available repellency test data garnered from various sources through 1964. Likewise, they coded molecules tested in their laboratory. On putting the information through a computer, they find that the groups most likely to provide mosquito repellency are aldehydes, amines, amides, amino-alcohols, a-halo esters, and ce-hydroxy esters. Armed with this information, Dr. Skinner and Dr. Johnson are making a variety of compounds. They send these to the University of California Medical Center in San Francisco where 52 C&EN SEPT. 15, 1969

The Kodak Scintillation Committee

Membership: Assistant Department Head, Analytical Services, Kodak Research Laboratories .. . Research Associate, Kodak Laboratory of Industrial Medicine, where animal studies trace metabolic fates of industrially significant compounds . . . Specialist in instrumentation to measure quantum yields . . . Specialist in radiochemical technique, the field in which he has counseled his Kodak Research Laboratories colleagues since the 1940's . . . Chemist assigned operational responsibility for the preparation, purification, and quality control of Eastman scintillation-grade chemicals . . . Chemist from marketing department, assigned to learn views of outside laboratories.

Dr. Howard Maibach and Derek Skid-

morg screen them in a dual-port olfactometer for repellency against female

Liquid scintillation-counting supplies:

Demand for them and insistence on quality are growing from Kodak's own laboratories, and growing still faster from the laboratory world at large. Wide-ranging use and importance of liquid scintillation-counting techniques justify the work of this committee. It strives to tune our quality standards to the cost of time wasted when standards are not what they should be. To share the benefit of this study with all users of liquid scintillation techniques, a program has been initiated with five of the most fundamental necessities. Detailed scintillation specifications are available for the asking. Use coupon below to request Informational JJ-59, "Reagents for Liquid Scintillation Counting." List Price

p-Dioxane

I p t . $ 3.75 12 x l p t . 41.05 1 gal. 22.20 4 x 1 gal. 80.70

(EASTMAN 13011)

(Scintillation Grade)

Toluene

(EASTMAN

1.60 ipt. 12 x 1 pt. 17.70 7.37 Igal. 4 x 1 gal. 26.80

13016)

(Scintillation Grade)

Naphthalene

(EASTMAN

1kg. 16.55 6 x 1 kg. 90.40

13007)

(Scintillation Grade) "PPO"

100 g. 28.70 1 2 x l 0 0 g . 313.35

(EASTMAN 13000)

(Scintillation Grade)

Phenethylamine

l p t . 19.15 12 x l p t . 208.80

(EASTMAN 13021)

(Scintillation Grade)

List prices shown are suggested prices only and subject to change without notice,

These "scintillation grade" reagents are available from any of the following nearby suppliers of all the other Eastman laboratory chemicals: B&A CURTIN FISHER HOWE & FRENCH

NORTH-STRONG SARGENT-WELCH WTLL

Eastman Kodak Company Eastman Organic Chemicals Dept. 412-L Rochester, N . Y . 14650 Send "Reagents for Liquid Scintillation Counting" JJ-59 to NAME ADDRESS

ZIP

miwm.mm

Aedes aegypti mosquitoes. The SRI workers also have devised a technique that allows them to test at equimolar levels compounds of widely varying chemical structure. This enables them to get a good and rapid approximation of the chemicals' relative degree of mosquito repellency. To date, none of the compounds they have made supersede D E E T . Two analogs—3,5-dimethyl-N,ZV-diethylbenzamide and 3-bromo-N,N-diethylbenzamide—are about the same as D E E T in terms of the duration of their repellency but have the drawback of being washed off the skin more readily. Another compound, pentafluorodiethylbenzamide, looked promising in the olfactometer tests but gives poor results when tested topically, a fact that points to a necessary balance between a compound's potency and its volatility. Another direction the SRI research is taking is toward designing a slowrelease mosquito repellent that would outlast D E E T . Specifically, Dr. Skinner and Dr. Johnson are exploring acetals, carboxamide acetals, ortho-esters, and ketals that might be hydrolyzed by the mildly acid nature of human skin and thus would slowly and continuously release an effective repellent. Along these lines, the dibenzyl ketal of cyclopentanone and the dibenzvl acetal of N,N-dimethyl formamide show repellency. But in these cases the whole molecule, rather than the products of hydrolysis, is active. "These are structures that hadn't been recognized as being mosquito repellent until now," Dr. Skinner says.

Goodman makes purine The research concentrate on 9-£-D-arabinofuranosyl-9Hpurine-6-thiol (C&EN, Aug. 18, page 41) should have identified Dr. Leon Goodman of Stanford Research Institute as the man who devised a procedure for making the nucleoside. Pfanstiehl makes research quantities based on this.

SEPT. 15, 1969 C&EN 53