Talk:Molecular binding

Covalent binding

In general scientific usage, irreversible covalent molecular binding is referred to as a chemical reaction, not as binding. Indeed, many biologists consider the definition of binding to be non-covalent.Rdphair (talk) 17:25, 11 January 2009 (UTC)

Nevertheless in specialized areas, the term "covalent binding" is often used, especially within the fields of medicinal chemistry and pharmacology. I have added a citation to the article to document this usage. Boghog2 (talk) 11:26, 18 January 2009 (UTC)

How very considerate of you, to pass over this any other opinions contrary to yours, via providing a single source to establish "often used". And how very consistent of you to argue on the basis of usage in "specialized areas," in this case. Leprof 7272 (talk) 02:46, 25 April 2015 (UTC)

Recent edits

@Leprof 7272: Wikipedia articles, especially the lead is suppose to be written in language that is should be understood by a wide audience and not a legal definition of the subject? Also that the lead is supposed to summarize the content of the remainder of the article? Much of the material that you included in the lead is not discussed in the body of the article. Finally the distinction that you are trying to make between "van der Waals" or close "electrostatic association" is artificial. Both occur simultaneously in all intermolecular interactions. Boghog (talk) 20:10, 24 April 2015 (UTC)

There is some accruing research to suggest that – huh? Wikipedia articles should simply state facts. If the research is still in doubt, it should not be stated. Boghog (talk) 20:29, 24 April 2015 (UTC)

I find the following replacement absolutely bizarre:

original

Molecular binding can be classified into the following types: non-covalent – no chemical bonds are formed between the two interacting molecules hence the association is fully reversible reversible covalent – a chemical bond is formed, however the free energy difference separating the noncovalently-bonded reactants from bonded product is near equilibrium and the activation barrier is relatively low such that the reverse reaction which cleaves the chemical bond easily occurs irreversible covalent – a chemical bond is formed in which the product is thermodynamically much more stable than the reactants such that the reverse reaction does not take place. References

replaced

A distinct case is that of a reversible covalent interaction, wherein a chemical bond is formed but where various changes in reaction conditions (e.g., a temporal decrease in the concentration of one of the unbound species), alongside thermodynamic constraints allow the covalent reaction to proceed in reverse. As in the case of non-covalent associations, the matter of whether a reaction is reversible or not is a practical one, though it is still conceptually useful to designate some reactions as irreversibly covalent (e.g., uncatalyzed amide bond hydrolysis in water) because the combination of the practical context of the reaction and the reaction's thermodynamics are such that the reverse reaction is, practically speaking, never observed. References You are questioning your own edits? Also In science one tries to tell people, in such a way as to be understood by everyone, something that no one ever knew before. But in the case of poetry, it's the exact opposite! — Paul Dirac Boghog (talk) 20:55, 24 April 2015 (UTC)

With respect to the edit summary: It simply is unfathomable that it would make the errors in the sentences to which it attached. The sentences to which is attached are rock solid. It is unfathomable that someone would question basic definitions. Boghog (talk) 21:27, 24 April 2015 (UTC)

The source is certainly rock-solid, but one citation, even if it states the categories at issue, does not establish the preponderance of this view. Please, for the sake of all editors visiting, first, paste in the exact text from this paywalled source, the source text supporting the Type categories that are written here, and so support that per Leach's and Houk's Miniperspective, they categorize the complexes referred to in the lede as including covalent interactions. Then, please provide the evidence that this is the generalized view, beyond this one article by computational chemists, via reviews from crystallographers and biochemists. When this appears from any editor interested, I will present any balancing view required. Le Prof Leprof 7272 (talk) 23:31, 24 April 2015 (UTC)

how about this

Hey Boghog i saw this content dispute b/c i watch your talk page. i agree that leprof's lead is not as clear, but there seems to be some good stuff here...

Chemical bonds may be classified as covalent (involving the overlap of orbitals, and therefore sharing of electrons between atoms), or non-covalent (involving attractive potentials exclusive of the sharing of electrons). Molecular binding exclusively refers to non-covalent associations between molecules to give complexes, and therefore is exclusive of the cases where two molecules become one discrete molecule through the formation of a new, electron-sharing covalent bond. As no chemical bond is formed between the two interacting molecules, it is reasonable to expect that the association is fully reversible, and this is often the case; but it is not always so, for instance in the case of high affinity, tight binding inhibitors. As well, natural examples of very high affinity are known, e.g., the case of the protein streptavidin and its extraordinarily high affinity for vitamin B7/H (biotin, dissociation constant, K_d ≈10⁻¹⁴ mol/L, under certain experimental conditions). In such cases, as the reaction conditions change (e.g., the protein moves into an environment where biotin concentrations are very low, or pH or ionic conditions are altered), the reverse reaction can be promoted (cf. the Bohr effect in the dissociation of ligands from hemoglobin, in the lung versus peripheral tissues); even so, the streptavidin-biotin interaction is one of the strongest non-covalent interactions known in nature.

References

can we not use this in some way? i particularly appreciate the definition of complex from a 2012 source, and examples at the end. Thx Jytdog (talk) 22:16, 24 April 2015 (UTC)

Re-added a simplified version of the above. Boghog (talk) 23:08, 24 April 2015 (UTC)

So the earlier text was incorrect or valueless, and deserving of full reversion, until someone else questions you… How very funny you are. This is reminiscent of poker players I have seen in the U.S., at tournaments, that call the blind (automatic, required initial bet)… until another player raises. Then, and, only then, do they appear to realize their cards are worth more. In that venue, such is considered a most immature manner of play. Leprof 7272 (talk) 02:53, 25 April 2015 (UTC)

In arriving here today, the errors I sought to correct—based on a standard conceptual frameworks taught in universities today—were that the complexes being referred to:

• are not only biologic,
• are not all weak,
• if non-covalent are not all practically reversible,
• are not by ay stretch limited to pairwise interactions (a correction Boghog himself made earlier but reverted here), and
• are not widely and generally understood by those teaching this to include the non-covalent (though as always, a minority of sources can be found that uses a definition that includes the covalent).

When these subjects are taught, it is generally done, e.g., referring to the formation of a complex (non-covalent associations) prior to covalent bond formation, i.e., complex formation before the reaction resulting in the covalent adduct. While I am sure that the idea of a "covalent complex" can be found and sourced, it is by no means reflects the preponderance of opinion about the best way to differentiate between experimental observables, and to describe them to students.

WIth regard to the complaints regarding chosen language, i.e., status of the draft at the time of Boghog's jumping on, I can only say that as usual, his impatience led him to intervene before I was finished for the day. What it would have looked like when completely done, we will never know. As always, I propose that had this returning editor waited to bit before responding, so the days edits could be finished, a civil interaction might have ensued. But I will not waste further time here. Who am I to have an opinion on this content? My last, small molecule-protein crystallographic work on the affinity of ligands in complexes formed prior to Schiff base formation, and the mechanism of a unique Mannich-base reaction resulting from prior affinity of a unrecognized "suicide inhibitor" with the same targets—these pale before Boghog's inevitable self-confident persistence.

I therefore cede this additional definition game to Boghog, leaving him to insult others at this article, hereafter. I can only apologize for stumbling upon his turf, as it is clear now that he had the earlier interest in editing here, and so there is no hope for another well-educated individual with differing views to contribute. I have learned not to expect AGF or patience, and so depart this article to save the time of all involved, leaving Boghog's turf to him. Last word is his. Leprof 7272 (talk) 22:33, 24 April 2015 (UTC)

No where in the previous version was it stated that molecular binding was only biologic or only weak. At worst, this was an error of omission. Thank you for adding these. Somewhat simplified variants are included in the current version. Boghog (talk) 23:47, 24 April 2015 (UTC)

You are right, the bulk of the article being about biological examples, and absolutely no abiologic, was (and remains) a significant error of omission in your article. The addition of text without sourcing to the lede does not rectify anything, it aggravates it. With you hounding again, my departure is again forced, and I will leave it to you to fix the issues. The "weak" phrasing, on the other hand—worse, appearing as "loose," see [1], as "A molecular complex in turn is a loose association involving two or more molecules"—this was well into your editing history at the article, and so no, not an error of omission, but of commission. That said, I was first, appreciative that under the watchful gaze of a couple of other editors, you found some value in my edits (though the scorn was poured pretty thickly before their arrival—did you notice the change in your tone/approach?). However, I was and am less appreciative of the hounding within 15 mins of my last apparent edit here—not really last, I had another section open, answered a phone call, and came back to find myself reverted—that you saw fit to follow me here. You had been absent for 27 months, and yet, with my appearance, you felt compelled to return and revert me—and worse, only to accept value of my edits after other editors came along. Seem personal to you, at all? However understandable this might be at some base biological level, this I think deserves some further outside attention (esp. as it is the reason I do not edit in science much anymore). Cheers, au revoire, here, anyway. What's yours is yours. Leprof 7272 (talk) 03:27, 25 April 2015 (UTC)

sorry the two of you have tangled. Leprof 7272 if you intend to do a bunch of work, it is often useful to place a template:Under construction template on the page if you want peace... you never know how closely someone else is watching. the last bit is kind of show-off-y by the way - you both have expertise here  :) Jytdog (talk) 23:50, 24 April 2015 (UTC)

Thank you, Jytdog, for this advice; would that another very experienced editor have only made this suggestion months ago, perhaps some conflict could have been avoided. Le Prof Leprof 7272 (talk) 01:23, 25 April 2015 (UTC)

Discrepancy now exists

…between the lede and Type sections. One says non-covalent, the other lists covalent. Leprof 7272 (talk) 22:44, 24 April 2015 (UTC)

The key phrase in the lead is "normally weaker". Molecular binding encompasses a spectrum from completely non-covalent to weakly covalent to reversible covalent. It can be argued that reversible covalent should not be included in molecular binding spectrum, but in common usage, it often is. Also as a practical matter, the distinction between the three classes is rather fuzzy. Boghog (talk) 23:01, 24 April 2015 (UTC)

All the foregoing in one editor's humbly emphatic, but—you must admit—poorly sourced opinion. See below. I offer a source using the language differently (actually two books, but only one author, so let's say one source). Let's call it even in terms of usage sourced, and so a difference of opinion. I cede your right to be right on your slim evidence, since you came to this article first. To secure your stakeholding claims, why not make sure you go to all articles of potential mutual interest to us, before I can. I assure you I will not make the mistake again to tread on your turf. Peace and article inaccuracy is my new credo. Cheers. Leprof 7272 (talk) 02:35, 25 April 2015 (UTC)

"Irreversible covalent" is included as a book-end for completeness and the boundary between reversible and irreversible covalent is not absolute. Boghog (talk) 23:20, 24 April 2015 (UTC)

But confusing as a category to include in an article about complexes, if the intention is not to convey that "Irreversible covalent" is not a category of molecular binding... to any that reads that does not know better. But you always have your reasons, and always, in the end, know what is best for your articles. Leprof 7272 (talk) 02:35, 25 April 2015 (UTC)

I would invite other editors that are interested in the article, but disinterested in the sides of this debate, to sample reliable reviews and primary literature to see what's the common usage [regarding "covalent complexes" and ""covalent molecular binding"] in this area. In the mean time, even if shown eventually to be best presented other than how they are, the lede and Type lists should be made consistent. Leprof 7272 (talk) 23:19, 24 April 2015 (UTC)

i took a stab at resolving this. i think complexes are generally non-covalent, but sometimes covalent, no? (that is to both of you!) Jytdog (talk) 00:08, 25 April 2015 (UTC)

In my view, @Jytdog:, in the hands of the best in the business (and the preponderant usage) is that complex implies non-covalent, and the term adduct is used if there is experimental evidence (kinetic, crystallographic) that a covalent bond is formed (see paragraph with links to RA Copelnad books, below). But who am I. Another is the EIC, here and he calls the final shots. Leprof 7272 (talk) 02:35, 25 April 2015 (UTC)

It honestly had not occurred to me till I saw this discussion that anyone would object to using the terms "binding" or "complex" to refer to covalent interactions. Try this recent paper on covalent ligand design methodology, which uses those terms with absolutely no self-consciousness. I don't think common usage in biochemistry/pharmacology/computational chemistry circles reflects what you've quoted from IUPAC.

I like Brian's work, @Opabinia regalis:, but with respect, even if he uses "covalent complex" or a similar parlance in that primary source, he and his colleagues are computational chemists, and not enzymologists/biochemists, pharmacologists, or crystallographers, the primary groups that study real binding (as opposed to virtual screens performed to develop hypotheses about what might bind). In this regard, skim UChicago's/Merck's RA Copeland, 2005/2013, Evaluation of Enzyme Inhibitors…, 225ff and passim, [2] or [3], or RA Copeland, 2004, Enzymes, 318ff and passim. [4], for the way covalent and non-covalent are used, the former with "adduct" the latter always with "complex." Or search JBC, and tell me if you see the words the concepts of "binding" and "complex" manage to slip through to refer to covalent adducts. Having reviewed and published in this area, we would consider not distinguishing in terminology between the two a very loose use of language, and we have, in fact, had editors insist on vary careful and clear wording to differentiate between the Michaelis complex, any other complex on the reaction manifold, and the final covalent adduct that formed (in papers describing the mechanism of formation of covalent inactivators of enzymes; see Copeland on this topic). Moreover, the importance of the distinction underlies the choice of terminology applied to "covalent catalysis" (i.e., identifying it, on the basis of the intermediacy of a covalent adduct, as a special class, distinct from other mechanisms involving non-covalent complexes, see Copeland again, on this topic). The reason for making the distinction is very practical: The ways and ease with which that one measures simple, reversible binding are quite distinct from what one must do if a covalent intermediate is involved in an enzymic mechanism. I am a big fan of the biochemists at two major pharmas with whom I have worked, in making this repeatedly and emphatically clear. However, who knows, perhaps this other editor insisting on his three bullet points is prophetic, so that as we know more all such categories will go away. I can only say what I know to be the preponderance of good current opinion on the matter (which he thankfully has acknowledged with tone-down edits, while still insisting, per usual, to open with on the more narrowly held perspective/bullets, burying qualifications in the text that follows). But I have given up trying to change the bloke. Cheers, yours to work out with him, I am not editing here any more. Le Prof Leprof 7272 (talk) 02:15, 25 April 2015 (UTC)

With respect to some of the above discussion, writing a reference work is not the same as writing a textbook, and IMO Wikipedia's "house style" has gotten less didactic over time. How you'd choose to present the topic in a classroom setting is only peripherally relevant to a reference article intended for a) a more diverse audience that b) isn't going to be sitting in the classroom to hear the next lecture. Opabinia regalis (talk) 00:15, 25 April 2015 (UTC)

that was fun to watch. Jytdog (talk) 00:46, 25 April 2015 (UTC)

Except, @Jytdog:, for the unfortunate fact that through his series of edits, the binding protein streptavidin now appears, via context, to be an enzyme. See that separate Talk discrepancy section below. Le Prof Leprof 7272 (talk) 01:28, 25 April 2015 (UTC)

Short replies to a long post:

1. I'm fairly sure that the Shoichet group - and most virtual screening types - would answer to 'molecular pharmacologist' before 'computational chemist'.
2. At the risk of not taking my own advice, I think I can say that my fields of interest freely use terms like "covalent complex". I imagine the best solution is to explain the difference in terminology and usage, if a source can be found acknowledging the variations.
3. The difference between reversible and irreversible covalent compounds is essentially a matter of biologically relevant timescale, so I'm not sure that trying to finely parse the distinction is all that useful here.

Opabinia regalis (talk) 06:19, 25 April 2015 (UTC)

A pleasure to engage you on these things, @Opabinia regalis: There is always a distinction between language use, in verbal communications, and how that language is formalized on publishing. In supporting a crystallographic screening group, I routinely heard the same word pairing, but can assure you it did not make it into the final published work. I stand by the proposition that the preponderance of best published and teaching sources differentiate in language between covalent and non-covalent, both in inhibition vs inactivation, and in terms of describing the associations between molecules (see long preceding paragraph). And without reiterating further my admiration for the Leach and Shoichet effort, I will simply say that the literature is clear about how all involved view hits from computational screens versus brick and mortar screens. While great strides have been made in improving scoring after computational docking, there is no gainsaying that no one much believes the results until the bench experimental data are in. (Otherwise, my assignment of computational and informatics monikers was by no means intended as pejorative; I have never had closer, better, more supportive collaborators than from these fields.) FInally, I agree about the timescale point, and drafted this point into my re-edit of the Types section (using the word temporal), which was part of the text that was carte blanche reverted. Not only does it depend on timescale, but also on the conditions of the reaction. As Prof Halpern was wont to say, in taking to task biochemists making thermodynamic arguments—and this was the basis for my objection to the continuing loose use of the article's thermodynamic language—when, e.g., a macromolecule is moved from one environment to another (as Hb in the lung versus peripheral tissues, my example), the "reverse reaction" being characterized is actually no longer the same reaction at all—different pH and other metrics of ionic environment, so different protein structure, and different concentrations of reactants, etc.— and so the reaction manifold (and its thermodynamic description) is no longer the same as the forward reaction. But this careful mechanistic view adopted from this thought leader is so far ahead of what one sees with regard to subtlety here, it is almost not worth mentioning. Leprof 7272 (talk) 18:23, 29 April 2015 (UTC)

Further discrepancy noted, after Boghog edit

The text reads…

Molecular binding can be classified into the following types: [1] non-covalent… reversible covalent… irreversible covalent… . Molecular binding exclusively refers to non-covalent associations between molecules to give complexes.

This is a further discrepancy that now must be addressed. Emphasis added. Leprof 7272 (talk) 23:49, 24 April 2015 (UTC)

Asked and answered above. Boghog (talk) 23:55, 24 April 2015 (UTC)

On this, the gold book page is the definition of a complex. I edited the article to make that clear. Jytdog (talk) 23:57, 24 April 2015 (UTC)

Per Chemistry MOS: International Union of Pure and Applied Chemistry (IUPAC) provides recommendations and definitions for nomenclature and terminology. Wikipedia editors strive to be mindful of IUPAC's advice but do not follow this advice rigidly, especially when the advice deviates from mainstream usage. Furthermore, the scope of this article is broader than chemistry. It also includes pharmacology. Boghog (talk) 00:05, 25 April 2015 (UTC)

Key here is this editor's self confidence in determining "mainstream usage." He and I disagree about it, but he has provided the single source he needs to retain his perspective in his article. Matter ceded; in my experience, one cannot prevail against him, regardless of what the preponderance or best sources might say. Leprof 7272 (talk) 02:43, 25 April 2015 (UTC)

The IUPAC Gold Book definition of complex states in part "The bonding between the components is normally weaker than in a covalent bond." Hence this definition does not exclude covalent bonding. In addition, an adduct is a type of complex ("whenever appropriate, [adduct] should be used in preference to the less explicit term complex") where there is a change in connectivity (i.e., bond) between the two species. The change in connectivity can involve covalent bond formation as in Meisenheimer adduct. Hence the IUPAC definitions certainly include covalent bonding in complex formation. In the fields of biochemistry and pharmacology, a ligand is usually defined as a small molecule that forms a complex with a biopolymer such as a protein. Furthermore there are numerous references to covalent ligands in the literature (see for example PMID 20042594 and 7922033). Boghog (talk) 06:38, 25 April 2015 (UTC)

The argument for "covalent ligand," @Jytdog:, @Opabinia regalis: is a red herring, as are the two stray primary sources provided in support—the issue is preponderance of usage, not stray examples, especially primary sources; the vast majority of search cases for this word pairing bring up examples where the "covalent" is preceded by "non-". The same is true regarding the historic Meisenheimer complex example, marginal in terms of the generality of this usage, where even its Wikipedia article states it to be "a 1:1 reaction adduct" (precisely because it is covalent, and because there is a need to clarify the language used in its original naming, a name given before the structural nature of the adducts was absolutely clear). More forcefully and unequivocal is counter-argument regarding the use of the term adduct, per se.

In an encyclopedia, you cannot refer to things in all ways that all reputable individuals have in the past. You have to choose one, pedagogically sound way. My use of the term adduct is consistent with its use in IUPAC, other fine encyclopedias (e.g., see here [5]), and with the preponderance of literature usage (e.g., see here, [6]). Otherwise, this mini-essay is this editor's personal editorial interpretation (original research), and does not cite an array of simply interpreted additional secondary sources—cf. the abstracts of the foregoing "covalent adduct" biblio just given. The question is not whether he can argue in support of his opinion. The demand is for good secondary sources, and a good number of them, so that they can be compared to others and evaluated as to whether they represent the preponderance of expert opinion. (E.g., Brintannica plus Copeland plus Pubmed reviews provide on the order of 30 reliable, high quality covalent adduct secondary sources.)

There is no question that some publishing scientists will provide, in some primary and even a few secondary sources, examples of the use of the term covalent in conjunction with the term complex, however unhelpful and relatively rare it might be. We wish to establish the preponderance of clearly set forth, expert published (not editor) opinion, so that there is a basis for seeking consensus with other equally experienced editors. We know this editor's opinion, we know he fervently believes in it, and we know he wishes it it to remain at the forefront of the section whose edits he followed in to revert (subtleties or opinions of other editors be damned). Please hold him to providing what published experts think, in good secondary sources, where the categorizations do not require his strenuous interpretation to support a final conclusion—so the real discussion can begin. There is otherwise no need for reiterations of his already stated personal opinion, as one individual, working in one contributing field. He reverted, and has been challenged. He needs to do the appropriate research in the secondary literature, and give us all the results, so all can decide—rather than proof texting his firm opinion. Leprof 7272 (talk) 16:58, 29 April 2015 (UTC)

Further discrepancy noted, after Boghog edit

The edit leading to the phrase "example with tight binding inhibitor as in streptavidin" is a further discrepancy that now must be addressed. There is no connection between the earlier content bits regarding tight binding inhibitors and regarding streptavidin. the streptavidin-biotin case is not an example of tight binding inhibition. Leprof 7272 (talk) 23:54, 24 April 2015 (UTC)

{{sofixit}} diff Boghog (talk) 00:01, 25 April 2015 (UTC)

Apologies, but who would be so foolish as to rush in to correct mistakes made by another editor who has just quickly reverted them—do you read what you are writing, to see how it comes across? Ones reserve at touching a reverting editors handiwork is all the more if s/he enters into the editing session before the first editor has finished with their session's work. But it would require patience, I suppose, to wait a day and see what a final product would look like, before jumping in. I think Pascal would argue that if you allow the time, the work might improve (Je n'ai fait celle-ci plus longue que parce que je n'ai pas eu le loisir de la faire plus courte.), but what could he know. Bottom line, though, from me: you have no reason to expect anyone to edit with you (back and forth), or to otherwise return any courtesy, when you yourself exhibit such discourtesy, reverting-before-discussing, especially with editors with whom you have had past relational issues. So, in re: {{sofixit}}, Physician, heal thyself. AGF at the start of a new editing interaction. Look into the mirror regarding collegiality, rather than breaking it to use the shards as weapons. As long as you act as you do, when you come, I go vis-á-vis continuing participation. Leprof 7272 (talk) 01:51, 25 April 2015 (UTC)

 Done but  Not done. The edit performed by the reverting editor after the "sofixit" directive improved the remaining text, but streptavidin still will appear (to those not knowing any better), nestled as it is between enzyme content and enzyme footnote, to be an enzyme example as well. The the fix is in, but the text is not yet fixed. Le Prof Leprof 7272 (talk) 01:51, 25 April 2015 (UTC)

The point about placement of streptavidin is reasonable and has been fixed.

Regarding your 'primary source' tagging, I added an accessible review that discusses the complex and its relatives, but this case - citing a specific experimental result - is exactly the situation in which a primary source describing that result is called for.

On the rest, see your talk page (in a few minutes). Opabinia regalis (talk) 05:18, 25 April 2015 (UTC)

I concur, @Opabinia regalis: with the primary source comment here, if it is accompanied by a much more recent secondary source, supporting the importance and primacy claimed in the article for the example, based on the primary source. Cheers. Leprof 7272 (talk) 05:33, 25 April 2015 (UTC)

scope

this article is called "molecular binding". what is the scope? thanks. Jytdog (talk) 04:31, 25 April 2015 (UTC)

"Molecular complex" redirects here, so what you call that and what you think defines it is "in bounds" IMO.

The bulleted list sourced to the Houk paper is nice because it parallels the categories defined elsewhere in e.g. enzyme inhibitor. It is a little reductive, as Boghog mentioned way above, but that's maybe not clear enough in the article. Easiest solution would be to find a source that directly comments on the variations in usage. Opabinia regalis (talk) 06:42, 25 April 2015 (UTC)

The best nomenclature, @Opabinia regalis: per the books provided and cited above, is not inhibitor, but inactivator (see Copeland, passim), when it comes to small molecules that inactivate enzymes through formation of a covalent bond (and yes I know about "suicide inhibitor", see Copeland and his citations regarding that). Even were one to allow that the computational/informatic Houk-Leach categories are appropriate at the inhibitor article (without differentiating between inhibitors and inactivators), this does not imply they are appropriate in an article that defines the title concept by invoking "complex", where the clear preponderance of opinion and usage is that the term complex, as it is used across several molecular fields, implies a non-covalent association. Again, I have collaborated with/am otherwise a big fan of the two senior authors of this one primary source, but their usage, as interpreted by this editor, does not reflect the preponderance of usage regarding the critical term "complex." I have provided standard expert texts that offer the contrary opinion, and argue that, by Occam, the simplest way to reflect the bulk of chemistry, pharmacology, crystallography, and enzymology texts, reviews, etc., from the best sources and publishers, is to use different words to describe covalent and non-covalent associations. I will not do more work here, because I think no one has the stomach to persist against my hounding editor, when he sets his mind to an end, especially when it comes to his personally preferred definitions of things. Leprof 7272 (talk) 17:05, 29 April 2015 (UTC)

I reiterate

…that the appearance of three bullets in the opening "Types" section, two of which are about covalent bond formation (rather than focusing opening sections on the obvious primary and preponderant dictum of non-covalent association), moves the thrust of this article away from the preponderance of expert opinion about the meaning of complex as it is most widely used, in the areas of biochemistry, pharmacology, medicinal chemistry, enzymology, and structural biology. It also defies sound pedagogic practice of using more specific language rather than less, when engaging a population you wish to instruct (where the general language obscures distinctives that more specific language highlights). I will periodically show up to reminding the community of this, but will not interfere in M Boghog's oversight of this article. Le Prof Leprof 7272 (talk) 04:43, 10 May 2015 (UTC)

you are continuing the discussion about scope. the article is about binding generally. a complex is one result of binding. not every result. i just made some edits to the lead to clarify that. Jytdog (talk) 04:48, 10 May 2015 (UTC)