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DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: derekb.lowe@gmail.com Twitter: Dereklowe

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November 18, 2013

When the "c" in cLogP Stands For "Crazy" (Update: Fixed!)

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Posted by Derek

cLogP.png
I don't know how many readers out there use the cLogP function in ChemDraw, but you might want to take a look at the illustration here before you use it again. A reader alerted me to this glitch: drawing in explicit hydrogens sends it into an even stranger world of fantasy than most calculated logP values inhabit. There seems to be a limit, though, as that cyclopropane series illustrates. (Note that the "logP" function resists temptation).

PerkinElmer says that there are several logP calculating functions built in, but that cLogP is from BioByte. I don't think that they got their money's worth from them. Now, this isn't the first glitch like this I've seen - a lot of chemical drawing and searching programs choke on details here and there. But this is the sort of thing you'd have thought would have been fixed by now.

Update: it has indeed been fixed, according to the fast-acting Phillip Skinner at PerkinElmer. But apparently many of us out in user-land aren't using updated versions. For what it's worth, I have ChemBioDraw Ultra 13.02 v. 3020 - are others getting more reliable numbers with newer software?

Note: here's where the patch can be downloaded.

Comments (31) + TrackBacks (0) | Category: In Silico


COMMENTS

1. Hap on November 18, 2013 2:26 PM writes...

I like how putting the fourth explicit H on the cyclopropane restores ClogP to the correct value. Apparently there is a limit to the calculated enhancement of hydrophilicity by explicit H substituents (well, in the real plane, anyway).

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2. Anonymous on November 18, 2013 2:27 PM writes...

Surely these calculations are all accurate and prove that our "common sense" is wrong?

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3. Nate on November 18, 2013 2:55 PM writes...

And modellers wonder why the experimental people give them the side eye so often. You can wave your arms all you want but you are still making numbers up

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4. Curious Wavefunction on November 18, 2013 3:02 PM writes...

#3: Except that most modelers don't use Chemdraw for calculating clogP. Experimental people do.

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5. Anonymous on November 18, 2013 3:16 PM writes...

#3: Many modelers knew this issue long time ago, and have contacted ChemDraw people. At the company I'm working for, we've warned our chemists, and encourged them to use a webbased tool that standardize the structrues before ClogP calculation.

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6. Anonymous on November 18, 2013 3:20 PM writes...

This seems to be ChemDraw's implementation problem, not BioByte's.

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7. Anonymous on November 18, 2013 3:27 PM writes...

"standardize the structrues before ClogP calculation"

Is that standardized with or without explicit hydrogens?

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8. ScientistSailor on November 18, 2013 4:05 PM writes...

If you are using ChemDraw for cLogP calculations, you get what you deserve...

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9. @kayakphilip on November 18, 2013 4:10 PM writes...

Hi Derek,
Was this you or one of your readership? Whoever, you are either on an old version of the software or haven't updated with relevant patches. This was an issue a while ago, and got fixed. I do not replicate this on my version (v13).

We all wish software came out perfect, but that is rarely so. Software companies come out with fixes for stuff from time to time. Individuals and organizations do need to stay current on those fixes.

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10. watcher on November 18, 2013 4:22 PM writes...

Very funny. Should ask my neice, who is taking organic right now, is she knows the difference in the structures. Of course, I'd be appauled if she tried to expain them each as unique as shown.

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11. @kayakphilip on November 18, 2013 5:08 PM writes...

btw patches can be downloaded from here: http://www.cambridgesoft.com/support/DesktopSupport/Downloads/

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12. Anonymous on November 18, 2013 5:12 PM writes...

@Kayakphilip

My version (v12) gives the results Derek lists. Do you know how can we obtain these patches you mention?

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13. newnickname on November 18, 2013 5:31 PM writes...

"It's not a bug. It's a feature."

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14. @kayakphilip on November 18, 2013 5:45 PM writes...

@Anon #12 - patches are all available here: http://www.cambridgesoft.com/support/DesktopSupport/Downloads/

There is also access to our support there - and a knowledge base where you can often find a solution to common problems you may have. If there isn't a solution to a problem you encounter then log a bug and it will get tracked and followed up on. We can't fix things we don't hear about - although the cLogP issue we had heard about, and fixed.

Those on Twitter, you can also contact support there @PKI_InformatxTS

@13 newnickname - no, it was a bug. It was fixed though.

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15. Konrad Koehler on November 18, 2013 5:49 PM writes...

The problem originated with BioByte, but when I alerted them to the problem in the standalone ClogP program back in March of 2011, BioByte promptly fixed it and sent both me and PerkinElmer a bug fix. The problem is that PerkinElmer never included the bug fix in ChemDraw 12. I don't have access to ChemDraw 13 so I don't know if the bug was fixed in this version, but I have my doubts.

For a discussion, see the following http: web link

//forums.cambridgesoft.com/textthread.aspx?catid=12&threadid=565&l=en

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16. BTDT on November 18, 2013 6:13 PM writes...

I swear by ACD labs (Toronto ) software to do clogP calculations. So does SciFinder.

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17. Anonymous on November 18, 2013 6:30 PM writes...

@9 @Kayakphilip
OK, after reading your post more carefully, apparently the bug fix was included in ChemDraw version 13, but as far as I can tell, a ClogP bug fix patch was never released for version 12. Also, if you have known about this problem for so long, why haven't you alerted your users to this bug?

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18. David on November 18, 2013 6:44 PM writes...

Can't relay on it

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19. @17 Anonymous on November 18, 2013 6:56 PM writes...

I personally can't comment re v12 - I am trying to get a definitive answer to that. Sometimes fixes are only in the most recent release, sometimes they are back-ported to older releases, that is normal for all software.

We typically notify people who report an issue when that issue is resolved and direct them to the appropriate fix. We can't do that directly for people who don't report issues. There are many ways to communicate with us about any issues - the best way is the support forum here: http://supportportal.cambridgesoft.com/ This allows you to track the progress of whatever you report.

There are also public forums where common issues and solutions are discussed - useful examples from the portal are posted there for public availability. We also post announcements when new versions and new patches are released, and what those patches address. Here is an example: http://www.cambridgesoft.com/services/SupportNews/details/?SupportNews=50

So, we don't inform every user about every bug, nor about every fix. But we do try to provide relevant information, both generally (publicly) and proactively (direct to those who report).

I will pass on any suggestions as to other ways of communicating anything the readership would think is useful though. We are keen to be communicative and part of the community, without bombarding people with emails.

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20. @kayakphilip on November 18, 2013 7:16 PM writes...

I might owe you an apology - I was correct in that it is fixed in v13 on PC. There may be something wrong here on Mac. I apologize for leading you possibly astray - I, and another colleague, double checked your claims on our own systems but couldn't replicate them but I only run PC. I've now got a colleague to replicate on a Mac. I will continue to update as I learn more.

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21. jbosch on November 18, 2013 11:47 PM writes...

Yes, definitely the Mac V13.0.2.3020 does not include this patch and shows the wrong clogP.

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22. pessinest on November 19, 2013 12:44 AM writes...

Out of curiosity has anyone seen any problems along these lines in marvin or marvinbeans?

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23. Morten G on November 19, 2013 4:38 AM writes...

"(Note that the "logP" function resists temptation)"

Shouldn't the logP be experimental values from a table? The c in clogP is for computed/calculated, right? Or are you being facetious / making dad jokes?

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24. alig on November 19, 2013 8:00 AM writes...

@23 Chemdraw reports two different calculated log Ps. One is labelled ClogP, the other is labelled logP, but it is still calculated.

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25. Pete on November 19, 2013 8:41 AM writes...

At the risk of being pedantic it should be ClogP and not cLogP. A good test for logP predictors is how well do they handle different canonical forms like CN(=O)=O and C[N+](=O)[O-] (pentavalent nitrogen and ylid representations of nitromethane).

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26. Morten G on November 19, 2013 8:46 AM writes...

@24 Thank you.

That's pretty misleading though ;)

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27. CS RNA on November 19, 2013 10:30 AM writes...

Seems the issue fixed in the current version (13.0.2)

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28. TX raven on November 19, 2013 11:51 AM writes...

Does it matter?

I'm amazed at the value some folks give to cLogP calculations...

Has anyone ever learned something from these calculations they did not know before running them?

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29. @kayakphilip on November 19, 2013 12:33 PM writes...

All,

This was a known issue that was resolved with the release of v13 for PC. The fix was not included in v13 for Mac, for which we apologize and thank Derek and the community for bringing this to our attention. We are now actively investigating a solution and I will report as soon as I have additional information for the community.

In the meantime, users can avoid the issue of incorrect ClogP values by not drawing explicit hydrogens in structures to be analyzed.

I would like to personally apologize for any confusion I caused with my comments. I wasn't completely correct and hope this above clears up that confusion.

Finally, we are always happy to engage on this forum and elsewhere. Readers know we have done so in the past and I'm happy to do so again. There is no substitute though for reporting issues via proper channels - so I encourage people to report and track any issues on our support portal http://supportportal.cambridgesoft.com/ and use the knowledge base that is there. We are also happy to engage on twitter (our product teams are @ChemDraw, @PKI_Informatics and our support team is @PKI_InformatxTS)

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30. newnickname on November 20, 2013 12:13 PM writes...

@14 kayakphilip: "It's not a bug. It's a feature."

That, of course, is the classic response of all generic tech support to bug reports that many of us recognize as humor. But now you've irked me by not seeing it that way.

I was talking to Rubenstein at the Camsoft booth at an ACS meeting (YEARS ago) and pointed out several bugs and glitches that he IMMEDIATELY argued did not exist, that I was wrong and that everything was fine and dandy and wonderful.

We opened a ChemDraw and I showed him and he became a believer. One that I remember was a buggy "align on center" function. Anyone who wasn't cross-eyed and had better than 20-200 vision could see that items were NOT properly centered both in the display AND in the printouts thus requiring manual aligning on the grids or 'by eye'. Centering was fixed in the next release.

There were also many problems with Camsoft's implementation of encapsulated postscript. Every time I reported a problem, the initial response was a dismissive, "No, it works fine." Only by providing specific examples and copies of files did they finally fix that. It was Camsoft's implementation of the Adobe standards that got goofed up. That dragged on thru a couple of releases (because it was a low priority -- to them).

In the Mac OS, there was a way to write macros to run a series of commands within a program with a single command. In ChemDraw, I wanted to save my files in several formats: ("Save as [name].cdx; save as [name].eps; " etc.). I could never get that to work. Apple said it was the Camsoft implementation. Camsoft support couldn't get my examples to work, either. Bug or feature?

In the Pipeline is about the DRUG pipeline. If we could sell drugs like software, the drug industry would be in great shape!

"I took your drug and it nearly killed me."
Yes, but that's not a bug, it's a feature!

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31. Joe on November 21, 2013 12:58 AM writes...

Is that 5th molecule with the triangle called anarchane?

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