I Like to Draw Pictures of Random Molecules

[Nagelfar]

Nag, you just drew tropacocaine? I think it's known but a shitty stimulant...

Tropacocaine is planar (or am I mistaken?), can't the hydrogen be oriented one direction or another? I've seen quite a few compounds that get specific. (P.S. I know a hydrogen ≠ a "hydrogen acceptor", I was thinking simplicity, as the vinyl-Cl analog proved it wasn't necessary)

Can you draw anything else than phenyltropanes btw? I mean...what's the point?

I don't draw many PTs. Mostly cocaine analogs.

And it's because there's enough phenyltropanes, but not enough cocaine analogs proper.

 

[aced126]

The only planar parts of tropacocaine are the phenyl and the C=O double bond. The rest of the molecule is not planar.

 

[Nagelfar]

The only planar parts of tropacocaine are the phenyl and the C=O double bond. The rest of the molecule is not planar.

Even the implicit hydrogens along the entire circumference?

EDIT: since it has two open spots, probably one goes in each direction and is incapable of having them both facing that way? Another noob misunderstanding on my part. At least I'm doing something at the public library to learn things (unlike everybody on either side of me at the library, always just online to play solitaire; lets not get into an ad hominem there too though; I'll concede that they're learning how to be better solitaire players, but I digress). Just last year I learned that para was the benzene 4 and ortho 2, etc. At least I know Me = CH3. ;-p

 

[aced126]

Nope; any carbon which has 4 single bonds is not planar.

 

[Nagelfar]

Nope; any carbon which has 4 single bonds is not planar.

this:

is the same as:

and can't be this:

then?

 

[Solipsis]

"entire circumference"?

The phenyl hydrogens are included in the phenyl so yes of course.

If you mean entire as in also the tropane then no, like in cyclohexane there are all single bonds so sp hybridization. For carbon this means tetrahedral geometry which is not planar.

For C=O and phenyl the double bonds / sigma bonds are sp2 hybridized leading to planar geometry.

P.S. don't forget that e.g. O, N and S have lone electron pairs which are usually not drawn unless they participate in reactions / reaction mechanism drawing - each lone pair more or less takes up a place in the geometry like a single bond would. So even though in tropane the N counts 3 covalent bonds it is not planar like in a phenyl carbon.

I assume for you I'm saying too much, but look up 'ammonia geometry' to clarify.

--

Re: your post / question:

no the bottom one is incorrect because if you draw the tetrahedral geometry of such a single-bonded carbon, two bonds are drawn in plane with the 'screen' or paper you draw on. One hydrogen will here point towards us, this will be the solid wedge, the other hydrogen points away from us, that is the dotted wedge.
Again, check this: https://www.google.nl/search?q=sing...rome&es_sm=93&ie=UTF-8#q=tetrahedral+geometry

and in your mind rotate that structure - match it with drawing conventions.

 

[aced126]

this:

is the same as:

and can't be this:

then?

All of those molecules are the same.

A carbon is only chiral if it has 4 different groups attached to it. In the 3rd structure you drew, the 2 hydrogens wouldn't be in the same plane because they would have repulsive forces pushing one of the hydrogens to the opposite plane (going into the page; dashed bond). The angle between 2 different groups in a carbon is always roughly 109 degrees, due to the repulsive forces. You can prove this for yourself by considering a tetrahedron and working out the internal angle.

I strongly suggest you pick up a copy of this and spend some time with it. http://www.amazon.co.uk/Organic-Chemistry-Jonathan-Clayden/dp/0198503466

I think it's worth it considering that you spend so much time thinking about these structures. I had a much lesser knowledge than anyone here about chemistry (less than even pre-university) until I got that book about 6 months ago. You don't even need to spend that long reading it, and it's all relevant to this.

 

[Solipsis]

If you draw methane, you *can* draw two of the hydrogens with such a solid wedge - then those two stick out in our direction. The other two must then point away from us and none of them will be in plane with the screen/paper.

Here it's not possible because the ring is too constrained to make the angle unless you would rotate the entire molecule - and that would require clarification drawing the correct dotted-wedged bonds.

It's a bit silly - there is no reason to try and picture the structure that way so it only adds confusion - you could say that is why it would likely be considered incorrect. You only draw unusual bonds (such wedges) to make clear what kind of isomer you have.
Here there is no chirality at that position, none of it matters.

 

[Nagelfar]

I strongly suggest you pick up a copy of this and spend some time with it. http://www.amazon.co.uk/Organic-Chemistry-Jonathan-Clayden/dp/0198503466

I think it's worth it considering that you spend so much time thinking about these structures. I had a much lesser knowledge than anyone here about chemistry (less than even pre-university) until I got that book about 6 months ago. You don't even need to spend that long reading it, and it's all relevant to this.

It's much appreciate aced. If I ever get any money whatsoever, I will seriously consider it.

Solipsis, I'll take you thinking you're saying too much as a compliment that I have enough sporadic knowledge to know, but since you don't know what knowledge I hold or do not, because it's so spotty, I appreciate the thorough way of going about your response. So thank you.

 

[Dresden]

That's funny, aced126, I would've sworn you were at least in your 3rd year of university.

 

[DotChem]

tropacocoiane in 3D.. would that help?

 

[DotChem]

and cocaine..

 

[DotChem]

or simplified..ie omitting Hydrogen atoms...

 

[aced126]

That's funny, aced126, I would've sworn you were at least in your 3rd year of university.

Turned 18 a couple a months ago lol, going to uni next year. It's just funny how much one can learn if they can find a way to rationalise it and make it relevant.

 

[Nagelfar]

I have another idea/question: Might hydrogen donors/acceptors present a possible mechanism or pathway that acts the way autoreceptors do in downstream downregulation of activity elicited from bonding by way of ionic H-acceptor/donor bonding?

I recently re-read that N-Ethylmaleimide (NEM), used to interfere with the residues (serine etc.) at the hydrogen acceptor site at MAT, almost totally blocks (95% ) mazindol specific binding; but the effect of 10 mM NEM was prevented by just 10 μM of cocaine (neither 300 μM of DA or D-amphetamine "afforded significant protection" against this affectation from cocaine). Also considering that replacing the carbmethoxy (H-acceptor) with differing heterocyclic substituents found electrostatic traits to affect binding more than even having an H-acceptor.... So potentially, "atypical" DAT ligands like mazindol rely on their binding via hydrogen acceptor/donor interactions, and steric, conformational, and electrostatic factors are what cocaine mainly relies upon to bind. If so, the entire "increase in firing rate" instead of slowing of it, may potentially be mediated by this facet, perhaps neurons are able to "notice" hydrogen exchange between targeted sites but not binding that weighs more on the latter kinds of binding and therefore downstream mediating reactions are less likely to be provoked?

Turned 18 a couple a months ago lol, going to uni next year. It's just funny how much one can learn if they can find a way to rationalise it and make it relevant.

Congrats, that's an admirable start. I got my interest in chemistry/joined this forum at 25y/o and @ that time knew next to nothing(!)

 

[aced126]

I have another idea/question: Might hydrogen donors/acceptors present a possible mechanism or pathway that acts the way autoreceptors do in downstream downregulation of activity elicited from bonding by way of ionic H-acceptor/donor bonding?

I recently re-read that N-Ethylmaleimide (NEM), used to interfere with the residues (serine etc.) at the hydrogen acceptor site at MAT, almost totally blocks (95% ) mazindol specific binding; but the effect of 10 mM NEM was prevented by just 10 μM of cocaine (neither 300 μM of DA or D-amphetamine "afforded significant protection" against this affectation from cocaine). Also considering that replacing the carbmethoxy (H-acceptor) with differing heterocyclic substituents found electrostatic traits to affect binding more than even having an H-acceptor.... So potentially, "atypical" DAT ligands like mazindol rely on their binding via hydrogen acceptor/donor interactions, and steric, conformational, and electrostatic factors are what cocaine mainly relies upon to bind. If so, the entire "increase in firing rate" instead of slowing of it, may potentially be mediated by this facet, perhaps neurons are able to "notice" hydrogen exchange between targeted sites but not binding that weighs more on the latter kinds of binding and therefore downstream mediating reactions are less likely to be provoked?



Congrats, that's an admirable start. I got my interest in chemistry/joined this forum at 25y/o and @ that time knew next to nothing(!)

Cocaine relies heavily on H-bond interaction in the carbomethoxy group at carbon-2. Observe the difference between tropacocaine and cocaine. I'm not fully sure if any electrostatic interactions are involved in cocaine binding to MAT. The only possible electrostatic interaction that could occur is if the basic nitrogen got protonated, and then this forming an ionic bridge with an aspartate residue or something. But, as shown in this study (http://www.ncbi.nlm.nih.gov/pubmed/12672255), a basic nitrogen is not required for DAT inhibition. This was one of the compounds synthesised in the study, only 6 fold less potent than methylphenidate itself (this suggests how important the basic nitrogen is; not very, in comparison to the carbomethoxy group):

 

[Nagelfar]

Cocaine relies heavily on H-bond interaction in the carbomethoxy group at carbon-2. Observe the difference between tropacocaine and cocaine. I'm not fully sure if any electrostatic interactions are involved in cocaine binding to MAT. The only possible electrostatic interaction that could occur is if the basic nitrogen got protonated, and then this forming an ionic bridge with an aspartate residue or something....

Not so:

Read this on heterocycles versus carbmethoxy (scroll past the table, the page number is correct)

 

[aced126]

Which particular heterocycles are you referring to? Most heterocycles are able to accept an H bond and can therefore be bioisosteric for the carbomethoxy.

 

[Nagelfar]

Which particular heterocycles are you referring to? Most heterocycles are able to accept an H bond and can therefore be bioisosteric for the carbomethoxy.

All of them.

Check the link: It's only two paragraphs and it basically shows why the H bond is not the factor of binding @ 2-beta; yes they can all accept them, but the discrepancies in binding affinities to variants containing the same heteroatoms do not account for binding changes between those, in fact it goes *inverse* to what would be expected if that were the case:

I quoted it below, but Greek characters like delta do not come across when speaking of quantum values, etc.:

The oxadiazoles 32c and 32h contained the same number and types of heteroatoms in the 2‚-substituent but the binding potencies were 8-folddifferent. Similarly, 32g and 32i both had one nitrogen and one oxygen in the 2‚-substituent, but 32g was 15 times more potent at the DAT compared to 32i.

To explore the possibility that the differences inbinding potencies of the 2‚-heterocyclic phenyltropanes were due to electrostatic interactions, molecular electrostatic potentials (MEP) in the vicinity of the atoms at positions A-C in the model compound (34; Figure 9) were examined. In this model, phenyltropane moiety was replaced by a methyl group. The differences in the electrostatic potential minima near position A (¢Vmin(A)) were calculated using semiempirical (AM1) quantum mechanics calculations after superimposing the heterocyclic and the phenyl rings to minimize steric and conformational effects. A strong correlation between ¢V min (A) and affinity at the DAT was obtained. The ¢Vmin(A) values for 32c, 32g, 32h, and 32i were 0, -4, -50, and -63 kcal/mol, respectively.

It should be noted that an increasingly negative Vmin in the vicinity of hydrogen-bond acceptor atoms is correlated with an increase in the strength of associated hydrogen bonds.

Thus, higher affinity at the DAT appeared to be associated with relatively less negative ¢V min values. In other words, the observed correlation was against the hydrogen-bond interaction in the heterocyclic analogues.

Thus, it can be stated that the binding of analogues possessing 2‚-substituents, which arecapable of participating in electrostatic interactions, may be dominated by electrostatic factors rather than hydrogen bonding.

 

[aced126]

All of them.

Check the link: It's only two paragraphs and it basically shows why the H bond is not the factor of binding @ 2-beta; yes they can all accept them, but the discrepancies in binding affinities to variants containing the same heteroatoms do not account for binding changes between those, in fact it goes *inverse* to what would be expected if that were the case:

I quoted it below, but Greek characters like delta do not come across when speaking of quantum values, etc.:

The link takes me to the start of the pdf only. But yes, I'll have to look into this in more detail as it does seem that H-bond donation is playing a lesser role than steric factors.