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November 28, 2012
Think Your Drug Is Strange-Looking? Beat This.
We have a late entry in this year's "Least Soluble Molecule - Dosed In Vivo Division" award. Try feeding that into your cLogP program and see what it tells you about its polarity. (This would be a good ChemDraw challenge, too). What we're looking at, I'd say, is a sort of three-dimensional asphalt, decorated around its edges with festive scoops of lard.
The thing is, such structures are perfectly plausible building blocks for various sorts of nanotechnology. It would not, though, have occurred to me to feed any to a rodent. But that's what the authors of this new paper managed to do. The compound shown is wildly fluorescent (as well you might think), and the paper explores its possibilities as an imaging agent. The problem with many - well, most - fluorescent species is photobleaching. That's just the destruction of your glowing molecule by the light used to excite it, and it's a fact of life for almost all the commonly used fluorescent tags. Beat on them enough, and they'll stop emitting light for you.
But this beast is apparently more resistant to photobleaching. (I'll bet it's resistant to a lot of things). Its NMR spectrum is rather unusual - those two protons on the central trypticene show up at 8.26 and 8.91, for example. And in case you're wondering, the M+1 peak in the mass spec comes in at a good solid 2429 mass units, a region of the detector that I'm willing to bet most of us have never explored, or not willingly. The melting point is reported as ">300 C", which is sort of disappointing - I was hoping for something in the four figures.
The paper says, rather drily, that "To direct the biological application of our 3D nanographene, water solubilization is necessary", but that's no small feat. They ended up using Pluronic surfactant, which gave them 100nm particles of the stuff, and they tried these out on both cells and mice. The particles showed very low cytotoxicity (not a foregone conclusion by any means), and were actually internalized to some degree. Subcutaneous injection showed that the compound accumulated in several organs, especially the liver, which is just where you'd expect something like this to pile up. How long it would take to get out of the liver, though, is a good question.
The paper ends with the usual sort of language about using this as a platform for chemotherapy, etc., but I take that as the "insert technologically optimistic conclusion here" macro that a lot of people seem to have loaded into their word processing programs. The main reason this caught my eye is that this is quite possibly the least drug-like molecule I've ever seen actually dosed in an animal. When will we see its like again?
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