X-Message-Number: 30346
Date: Tue, 22 Jan 2008 23:24:24 -0500
From: 
Subject: 1,3-propanediol

    Again, I am extremely appreciative of the
postings that Doug Skrecky has made on the
subject of what is the most important cryobiological
issue in cryonics: cryoprotectant toxicity. His
latest posting

http://www.cryonet.org/cgi-bin/dsp.cgi?msg=30337

is right on target. I too have come to believe
that 1,3-propanediol most likely has an enormous
potential as a non-toxic cryoprotectant.

  The biggest breakthrough in vitrification
technology in the last decade to have been
described in the literature to my knowledge is
the qv* model and its application, which appeared
in the 21CM 2004 classic:

http://www.ncbi.nlm.nih.gov/pubmed/14969679

http://www.21cm.com/pdfs/improved_vitrification.pdf

   The qv* model proposes that cryoprotectants
with a higher Concentration Needed to Vitrify (CNV)
are less toxic.  As a result of the qv* model,
ethylene glycol was substituted for propylene
glycol (1,2-propanediol) in VS41A and similar
vitrification cocktails. But 1,3-propanediol has
a higher CNV  than either ethylene glycol or
1,2-propanediol as shown in Table 2, page 347,
of  CRYOBIOLOGY 27:345-358, 1990:

Cryoprotectant........CNV

1,2-propanediol.......44%
ethylene glycol.......53%
1,3-propanediol.......57%

So it would seem to make more sense to use
1,3-propanediol rather than ethylene glycol.

   In my earlier posting I expressed skepticism that
ethylene glycol would result in calcium oxalate formation
and toxicity:

http://www.cryonet.org/cgi-bin/dsp.cgi?msg=30114

    I was thinking that ethylene glycol metabolism to
oxalate occurs primarily in the liver, and would be
less relevant at low temperature -- and where only
the brain is being perfused. Now I am not so sure.

     In the rightmost chart of Figure 3
of the 2004 21CM classic cited above,
solution 11 of Table 1 (mainly ethylene glycol)
is an outlier which is more toxic than the
model would predict. The model is kidney slices
and calcium oxalate is most toxic in kidneys.
The model would describe this outlier as having
a "specific toxicity" which is outside the
qv* model of "nonspecific toxicity". So
substituting 1,3-propanediol for ethylene glycol
could possibly reduce both "specific toxicity"
and "nonspecific toxicity".

     By extension, 1,4-butanediol could be even
better. Like formamide, 1,4-butanediol is such
a weak glass former that it cannot vitrify in
any concentration (no concentration is adequate
as a CNV). But like formamide and ethylene
glycol (and possibly 1,3-propanediol),
1,4-butanediol could potentially give enormous
assistance to the other cryoprotectants in
a vitrification cocktail .Or perhaps 1,4-butanediol
could be used in combination with 1,3-propanediol
or ethylene glycol or both.

   By the way I highly recommend

CRYOBIOLOGY 27:345-358, 1990

which you have apparently missed in your
literature searches. A number of excellent
papers that appeared in CRYOBIOLOGY over a
decade ago never made it into PubMed, and this
is one of them.

     -- Ben Best

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