Talk:Gadopentetic acid

structure

The ball and stick model is wrong. The Gd is 9-coordinate with bonds to all 3 N atoms and all 5 carboxylate groups. The ninth position is occupied by a water maolecule. It is the exchange of this water molecule with water molecules in the environment of the complex that makes the complex an effective contrast agent, by bringing water molecules from the patient close to the paramagnetic ion. (Signed Peter Gans)

I have added a new image. Please let me know if you think it looks right now. -- Ed (Edgar181) 15:22, 31 October 2011 (UTC)

Much better, but all carboxyl groups are deprotonated. DTPA was developed as a complexone similar to EDTA, but suitable for the larger cations like lanthanides and actinides. log K values for DTPA are 10.58, 8.6,4.3, 2.6, <2 so the protons are easily removed because of the chelate effect. The molecule as a whole carries 2 negative charges (whence DI-meglumine salt); Should that be included in the structure? The water molecule in the 9th position is missing.

I'm somewhat concerned about the use of trade names. In this particular case "dimeglumine" is misleading as the cation is the protonated meglumine molecule, not meglumine itself. Petergans (talk) 09:19, 1 November 2011 (UTC)

Looking at several databases (Chemical Abstracts, Chemspider, and CID 6857474 from PubChem), they all show gadopentetic acid with 3 carboxylates and 2 carboxylic acids. Even Aldrich sells it in this form. So in the absence of an amine base such as meglumine to deprotonate the last two acids (to convert gadopentetic acid to gadopentetate), the consistent information in reliable sources suggests the current structure (File:Gadopentetic acid.svg) is correct. If I recall correctly, WikiProject Pharmacology prefers the infobox to contain information for the parent active ingredient rather than salt forms or hydrates, even if the drug is mainly used in a formulation containing a particular salt form. Salt forms are to be described in the main text. The water molecule in the 9th position should only be there for gadopentetic acid hydrate, not the parent compound. Right now the infobox contains some content for gadopentetic acid and some for the meglumine salt, so maybe the box should be updated to include only data for gadopentetic acid and not gadopentetate dimeglumine (which I agree is not the best name for the salt form, but that appears to be the only name used.) -- Ed (Edgar181) 11:57, 1 November 2011 (UTC)

This is a tricky one. I accept that you are correct in stating that the neutral cmpound is marketed, but I don't know if it has the structure indicated - it may well be be a hydronium salt. What worries me is that the molecule which is active as the contrast reagent is certainly not this species. The original article (before I messed with it, 23 Oct.) stated "Gadopentetic acid (in the form of gadopentetate dimeglumine or Gd-DTPA) is a gadolinium-based MRI contrast agent". "In the form of" is nonsense, the acid and its salts are distinct compounds. The original chembox gave data for the dimeglumine salt. I'll have to leave this issue for the moment, due to other engagements. In the meantime, do as you think fit. I'll be back on the case in 3 week's time. Petergans (talk) 18:37, 1 November 2011 (UTC) I've just checked by stability constats database. Log K for GdDTPA^2- is about 23. No hint of a protonated species being formed in solution, so it's unlikely, though not impossible, that a protonated form may exist in the solid state. Petergans (talk) 19:48, 1 November 2011 (UTC)

Please look at the Sigma-Aldrich structure. http://www.sigmaaldrich.com/catalog/ProductDetail.do?lang=it&N4=381667|ALDRICH&N5=SEARCH_CONCAT_PNO|BRAND_KEY&F=SPEC

The structure (14 Nov) is definetely wrong. Carboxylic acids do not form complexes with metals, so there cannot be a bond between a carboxylic OH group and the Gd ion. Only carboxylate ions form complexes. This stricture applies to other stuctures such as Gadobenic acid. Petergans (talk) 14:10, 14 November 2011 (UTC)

Interesting discussion. We ran into a similar issue came up recently with DOTA, for which there are several articles in Wikipedia. A potentially relevant issue, albeit nit-picking, is that there is so little precedence for a carboxylic acid (vs carboxylate) functioning as a ligand. Certainly possible, but I have never seen it. It is the type of thing that pharmaceutical types would write. --Smokefoot (talk) 14:18, 14 November 2011 (UTC)

I'm perfectly willing to modify the structure if necessary, but right now it is consistent with what is presented in multiple reliable sources. Can either of you suggest some specific modification to the structure based on other sources? -- Ed (Edgar181) 14:26, 15 November 2011 (UTC)

The only completely reliable source for a structure is an X-ray crystallographic determination. We have done an extensive search of the literature and have not been able to find one for gadopentetic acid. It is true that the structure with bound OH groups can be found in some publications, but it is not reliable in the sense that it is conjectural; the structure appears to have been copied willy-nilly from one publication to another, perpetuating the original error. I have discussed this topic with colleagues at the University of Messina who are experts on coordination chemistry and we all agree that carboxylic acid residues do not form complexes. I can't suggest any modification as I have no evidence as to what the structure should be. Therefore, no structure of the Gd complex should be shown; you may think that a structure for this ligand (and others in the series) might be worth showing, however. In that case all the carboxyl groups will be protonated.Petergans (talk) 13:54, 16 November 2011 (UTC)

Well as we all know, especially with metal complexes, even the Xray structure doesnt give all the insights - protons can be difficult to locate and refine, and structures change from solid to solution. I actually thought that the deleted structure, although somewhat idealized, was far better than nothing. At least the "conjectural structure" should be inside the article. The people that use these things are looking for a general idea of connectivity, which the deleted structure provided. The main issue for me is that probably one water ligand is bound since the exchange of Gd-OH2 and free OH2 is the basis of the mechanism of action by these contrast agents.--Smokefoot (talk) 14:08, 16 November 2011 (UTC)

what matters for gadopentetate is the solution structure - a solid-state X-ray is not much help. Same issue for most drug molecules actually. I agree - show 5 carboxylates without protons and add the innersphere H2O - that's no more "conjectural" than most other structure in the Chemistry literature Brownturkey (talk) 20:55, 16 November 2011 (UTC)

I agree, the important structure is that in solution. It is not completely conjectural. There is strong evidence that the solution structure is the same as that determined in the solid state, e.g. measured stability constants for this species and complexones in general.

I cannot agree to an unreliable structure being shown. The only structure of interest is that of the di-anion, not the acid. Show this by all means; at least it is based on a crystallographic determination of the structure a salt of the anion. (Peter Caravan, Jeffrey J. Ellison, Thomas J. McMurry, and Randall B. Lauffer, Gadolinium(III) Chelates as MRI Contrast Agents: Structure, Dynamics, and Applications,Chem. Rev. 1999, 99, 2293-2352). Petergans (talk) 09:08, 17 November 2011 (UTC)

Title

The new structure is fine, but it is not that of gadopentetic acid. Maybe the title need to be changed to "Gadopentate"? The chemical formula C₂₈ ... is that of the dimeglumine salt. I have not checked the other items in the drugbox to see if they refer to the acid or the salt; consistency is needed. Petergans (talk) 13:51, 21 November 2011 (UTC)

Wrong molecular weight?

Hi,

I think the molecular weight is not right. It is 938.005 g/mol, not 545.56.

See PubChem link.

N

Wrong molecular weight?

The molecular weight was correct as it was before, as 545.56. The pubchem link referenced is not for gadopentetic acid. It is for the dimeglumine salt.

— Preceding unsigned comment added by 170.223.137.116 (talk) 14:26, 31 May 2017 (UTC)