Which Nitrogen in Histamine is Most Basic?

[herich]

Homework Statement

Arrange the nitrogen atoms of histamine in order of their decreasing basic strength.
http://img134.imageshack.us/img134/7339/histamine.th.jpg

Homework Equations

The more ready the nitrogen atoms donate lone pair, the greater the basicity;

The Attempt at a Solution

The rightest one must be the most basic.
But how about the other two? It must be related to resonance. But I just don't know how to work out the answer by drawing the resonance structure (how to draw this one~?)

* one more simple question: when a metal ion (say Cu2+) forms a complex with EDTA, what is the coordination no.? (count the no of ligand - 1 or the dative bond - 6 ?)

Thanks!

 

[chemisttree]

In one of the nitrogens of the ring system, the lone pair must be involved in any aromatic stabilization; the other nitrogen does not. If the lone pairs of that nitrogen is tied up in aromatic resonance, can it be a good base? The remaining nitrogen (in the ring) has its three bonds 'tied back' through its bonds in the ring system leaving the lone pair in an orbital directed away from the ring system but in the plane of the ring system. Unlike the aliphatic amine, inversion of the lone pair through the nitrogen system is not possible with this (semi)aromatic nitrogen's lone pair. How might that affect basicity?

 

[herich]

If the lone pairs of a nitrogen is tied up in aromatic resonance, it cannot be a good base. But, how can I know which nitrogen has its lone pairs resonating in the structure?

And what does "inversion of the lone pair" means? Do you refer to the upper nitrogen?

 

[chemisttree]

If the lone pairs of a nitrogen is tied up in aromatic resonance, it cannot be a good base. But, how can I know which nitrogen has its lone pairs resonating in the structure?

The lone pairs that can occupy space above and below the plane of the ring can become involved in the aromatic stabilization. Ones that are directed away from the ring and lie at right angles to the overlapping pi bonds cannot .

 

[epenguin]

If the lone pairs of a nitrogen is tied up in aromatic resonance, it cannot be a good base. But, how can I know which nitrogen has its lone pairs resonating in the structure?

“which nitrogen has its lone pairs resonating in the structure” is the same one bound to H (the other N donates 1 electron to the resonating structure). The answer must surely be ‘both’. In the case of imidazole it would be fifty-fifty, but when there is a substituent to make it asymmetrical as in histamine or histidine it will be both, but with a preference. So you are asking what is the preference and the answer apparently is the N atom farther from the substituent gets the H preferentially. http://guweb2.gonzaga.edu/faculty/cronk/chemistry/CHEM440/lectures.cfm?L=5
If you ask how you could predict that, I can’t see offhand and hope someone will tell us.

But in any case the two forms are in tautomeric equilibrium. You can easily see if you protonate the H-less N atom you can then easily flip the formal double bond and charge and a proton can dissociate from the other N. These are very fast reactions. Illustration in “Physiologically IMPORTANT Ionization States of the Histidine Side Chain” at http://spdbv.vital-it.ch/TheMolecularLevel/Goodies/Get2NoHistidine.html :
More stuff on the aromatic resonances and in comparable molecules at “histidine” in http://swift.cmbi.kun.nl/whatif/theory/Theory.html

These articles have a bit of enzymological context you don’t have to be expert on yet, but then that is the major significance of histidine on this earth.

 

[kanosaizo]

Hi,

does anyone know where i can find the pharmacophore of histamine or NA/A

 

[sjb-2812]

Hi,

does anyone know where i can find the pharmacophore of histamine or NA/A

What is NA/A? In any event, different biological targets may give you different structures as pharmacophores?

 

[kanosaizo]

Hi,
does anyone have an idea as to why histamine solubilise in water, now acetonitrile is soluble in water as well and used as mobile phase for Histamine for hplc. so why doesn't my histamine solubilise in acetonitrile?

thnx

 

[kanosaizo]

thnx sjb-2812 didnt think of it that way but the target is smooth muscle aorta. and NA/A is nor adrenalin and adrenaline.

 

[kanosaizo]

I'm doing a project on immobilsation of carbon nanotubes with histamine. upon adding EDAC and NHS to favour carbodiimide bonding between carboxyl group and aliphetic amine at histamine molecule, the histamine seemed to have bound somewhere else and lead to increase in acidity when treated with acid-base titration. these are the investigated functional groups onto oxidized MWCNTs surface (% w=w) :
20.83% carboxyl, 61.67% lactone, 8.33% phenolic hydroksyl,
and 9.17% hydroxyl groups.


does anyone know if histamine molecule prefer to form a bond with any of the other groups above? any help would be appreciated

kind regrads
kano saizo