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AS POSSIBLE CRYOPROTECTANTS
Jan. 30, 1998--Douglas Skrecky transmits the following:
Boutron P, and Baudot A. "Calorimetric Study of Aqueous Solutions of Diethylformamide and Dimethylformamide" Cryobiology 35(4): 329-330 December 1997
Aqueous solutions of diethylformamide (DEF) and dimethylformamide (DMF) have been studied by differential scanning calorimetry on cooling and warming betweeen -153 and 0 C. With DEF, no hydrate forms except during warming at 2.5 C/min after quenching. On warming, only the glass transition, the ice formation, amd melting are observed. With DMF, the thermograms are much more complicated, with hydrate formation. The last hydrate melts at -48 C. The wholly amorphous state could not be obtained with 35% (w/w) of any of these solutes. The critical cooling rate Vccr to avoid any crystallization is repectively 300, 75, and 20 C/min for 40, 45, and 50% (w/w) DEF. The critical warming rate Vwcr to avoid any crystallization from a wholly amorphous solution is respectively 10,000,000, 900, and 110 C/min for 40, 45, and 50% (w/w) DEF. For DMF, Vccr and Vwcr are respectively Vccr = 500, 35, and 7 C/min, and Vwcr 10,000,000,000 (from an almost wholly amorphous solution), 295, and 150 C/min for 40, 45, and 50% of this compound.
Therefore, the glass-forming tendency on cooling these two compounds is greater than glycerol and ethylene glycol, but less than 1,2-propanediol and levo-2,3-butanediol (Boutron P, Cryobiology 30: 86-97 1993). The stability of the wholly amorphous state on warming these compounda is also greater than glycerol and ethylene glycol and less than 1,2-propanediol and levo-2,3-butanediol. These amides are, on warming, more efficient than DMSO at the concentration of 50% (Boutron P, Cryobiology 30: 86-97 1993).
According to the manufacturers, DEF is less toxic than DMF. These compounds could be good cryoprotectants if they are not too toxic, and if one can avoid damage due to the hydrate of DMF.
COMMENTS: As many readers will recall, there has been considerable interest in recent years in DMF and other amides as cryoprotectants. (We might say revival of interest, since some of these compounds were studied many years ago.)
Readers also recall that Boutron and others have spent many years trying to perfect cryoprotection through vitrification--formation of "glassy" or non-crystalline solid state storage at temperatures that are low, but not as low as that of liquid nitrogen. Avoidance of ice crystal formation can help avoid or reduce damage. One of the problems, however, is that vitrified solutions tend to crystallize upon rewarming, unless the rewarming is very fast. Critical cooling rates are also high.
To get an idea just how fast the temperatures must change, look at the figures above. DMF at 50% must be cooled at least 7 deg C per minute, and rewarmed at least 150 deg C per minute. At lower concentrations the rates are MUCH higher.
Even 150 deg/min is extremely fast warming for a specimen as large as a human brain, and can only be achieved, as far as is known, by use of microwave or radio frequency heating or something similar. To do this uniformly is a formidable technical challenge.
Note: Dr. Boutron is author of LE VIRUS DE JOUVENCE (la Pensee Universelle, Paris, 1975), a book promoting immortalism. --R.E.
Email us at: cryonics@cryonics.org