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I Like to Draw Pictures of Random Molecules

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^ Yeah, that's how someone would end up trying to rob a box of fentanyl patches or eat 500 pills of Imodium in a couple of days when they try to get out of that situation. And even then it would be difficult to balance the amount of opioid and antagonist in their body to not OD instead. About as demonic as "normal" people see drug use is.
 
Someone kind enough to help me find a mobile application, structure drawing molecular chemistry, program for Android phone that's free?

Even one that works online that'll screen capture and host for you at a click? I know how to supposedly screen capture on this phone (volume down and off pressed at same time) but I can't figure where it goes or if it even saves.
 
If the benzene can afford substitution when it is chelated as a chromium tricarbonyl, if so, I've found my personal very own 'methylenedioxy' to put (OK typo gods, pit) up against, well, everything ; -b

e.g. chromium tricarbonyl para cis propenyl phenyltropane.
 
Nothing's said anywhere about the cinnamoyl ester of tramadol, or a dextropropoxyphene with the propionate replaced with cinnamate... Difficult to tell which hydroxyl in these is 'equivalent' to the one at 14-position of oxycodone.
 
sekio said:
Unfortunately deprotection is simple ass O2 exposure.
Click to expand...

Since it's nonplanar, probably even with a napthyl, eh?

Chromen-2-one.png


^7-(((1R,3r,5S)-9-Azabicyclo[3.3.1]nonan-3-yl)oxy)-2H-chromen-2-one, w/o the chromium tricarbonyl it is:
5-HT-uptake IC50(μM)
0.0013
DA-uptake IC50(μM)
0.24
NE-uptake IC50(μM)
0.076

The 9-methyl azabicyclo has even better affinity for DA @ 0.15, and is more selective for it.
 
I suspect that chromium carbonyl makes for a poor drug. as most metal carbonyl compounds tend to be amazingly toxic as they are effective delivery devices to give lipophilicity to zero valent metals and direct them to the places they can do the most harm to enzymes. c.f. nickel carbonyl

also they add extra bulk and block pi-stacking of the phenyl group = less effective binding
 
sekio said:
also they add extra bulk and block pi-stacking of the phenyl group = less effective binding
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except in the case of troparil and the phenyltropanes, the study found them to bind better and have higher affinity at DAT. I am assuming the DAT ligands, at least, have in general a chance at benefiting in many chance cases because of which.

Anyway, due to that simple finding, something else novel has to jump at me in terms of QSAR until my biometallic fetish runs it's course. In the meantime, what *would* the tricarbonyl aryl of methamphetamine do in vivo?? No in vitro studies? I'm still guessing it couldn't find its way into MAT as a substrate but may work as a really tight fitting pump ligand. If it did work as a substrate, that in itself would be worth finding out.
 
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you kind of answered your own question then, either (1) the induced acidity of the benzene ring (which would probably make 4' hydroxylation by CYP easier, if the molecule can fit and nothing de-chromiums the whole deal), (2) the sterics involved, or (3) some electrostatic attraction from some moiety "across the pocket" in the DAT protien towards the carbonyl ligands is increasing affinity. I think you are also a prime contender for "most Ivory Tower academic chemical 'tool' misrepresented as a drug" contest.

also, I would be very suspicious of any binding figures unless there's some rigorous proof that nothing silly happens metabolism wise. I have a hard time nothing happens to the Cr or its ligands in the variety of environments in a cell and its environ. Displacement of the CO ligand by thiols, amines etc could account for differing species present and also is a source of nasty CO.

I do not think there's any magnetic attractions going on as most amino acids and protiens lack any way to sense or respond to magnetism.

while we are on the topic of tropanes, mr. lenz says that this is an opioid:
N4PVoly.png
 
I think you are also a prime contender for "most Ivory Tower academic chemical 'tool' misrepresented as a drug" contest.
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I'll take that. Esp. if it's "purposeful" misrepresentation. 😉
also, I would be very suspicious of any binding...
I do not think there's any magnetic attractions going on as most amino acids and protiens lack any way to sense or respond to magnetism.
Click to expand...

I think the Singh article, comparing it to the cyclopentanes Ruthenium pi stacked, comes to the opposite conclusion, as the size would be equivalent to the Chromium tricarbonyl, and it's all magnetic
while we are on the topic of tropanes, mr. lenz says that this is an opioid:
N4PVoly.png
Click to expand...
Like a tropaned Demerol
 
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as the size would be equivalent to the Chromium tricarbonyl
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Uhh, they are also electrostatically quite different, but IIRC 3 CO molecules are way smaller than a tetramethylcyclopentadiene.

it's all magnetic
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From what I understand, chromium and nickel carbonyl both are diamagnetic thanks to the CO ligands pushing electrons from singly occupied states to lower energy states where they are paired up.

I was under the impression that single atoms/molecules in solution are too rapidly scrambled by thermal motion to form effective magnetic domains.

(Did anyone ever manage to get a NMR spectrum of the metallocarbonyl bound tropanes?)
 
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sekio said:
Uhh, they are also electrostatically quite different, but IIRC 3 CO molecules are way smaller than a tetramethylcyclopentadiene.
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Solid cone angles he noted were around 130° to 180° respectively. 30% larger and on that scale he noted it as equivalent.

The binding to selectivity of the Ru was much closer, 1.7, so interesting in that capacity

The discrepancy in binding for the two benzene metal chelates is assumed to be due to electrostatic differences rather than their respective size difference. The solid cone angles, measured by the steric parameter (i.e. θ) is θ=131° for Cr(CO)3 whereas Cp*Ru was θ=187° or only 30% larger. The tricarbonyl moiety being considered equivalent to the cyclopenta dienyl (Cp) ligand.
Click to expand...
 
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A constellation of methadone analogs (& one propiram analog):
gXvoP6w.png

8cM2Q3k.png


I have no data on the cyclized analogs but I bet they are active if not also very potent.

The phosphorous methadone analog is very neat even though it isn't super duper potent.
Also neat to see an aldehyde as an active opioid, are there any others?
 
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I saw this in the Journal of Natural Products today and thought it was neat. I can't remember ever having seen an (N-methyl-2-aminopropyl)phenyl moiety in a natural product before... and with an (S) configuration, no less!

np9b01168_0011.gif


The authors propose that this moiety is biosynthetically derived from a tetrahydroisoquinoline:

np9b01168_0010.gif


So where does the alpha-methyl come from? Most tetrahydroisoquinolines in nature start with dopamine (see compounds 17 and 18 in the figure above, for example) or another biological phenethylamine. Does this mean there's an alpha-methylphenethylamine biomolecule involved here? Unfortunately, no. Strangely enough, these naphthoisoquinolines get their entire carbon structure via polyketide biosynthesis:

c9np00024k-s2.gif
 
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