The ChemConnector Blog by Antony Williams

Last year I co-authored a book chapter in a book regarding Chemical Information Mining. A recent review for the book was recently written by Peter Willett and it was nice to get a good mention for our section:
“This book discusses the use of text-mining techniques that would enable such operations to be carried out by purely computational means. The techniques are clearly attractive in terms of cost-effectiveness but would appear, from this volume, to require considerably more research before they can provide a realistic alternative to human processing. Two chapters - Automated identification and conversion of chemical names to structure-searchable information  and Identification of chemical images and conversion to structure-searchable information  - stand out, providing critical, wide-ranging reviews of their respective topics that I am sure that I shall return to in the future. ”

It’s nice to be appreciated for “after-hours” work.

A friend of mine passed this on to me. it is an example of creative brilliance…I hope my children are a part of this future….

During my career I have had the opportunity to work with some of the best scientists. During my >10 year tenure at ACD/Labs I directly managed the NMR product line for a number of years and was involved with the development of both the NMR prediction and Computer Assisted Structure Elucidation software. Over the past couple of years since leaving ACD/Labs I have continued to co-author articles with two of my ex-colleagues, and still friends, Kirill Blinov and Mikhail Elyashberg. Three of these articles were released in one work. If you are interested in NMR prediction and CASE systems you might find these articles interesting.

The application of empirical methods of 13C NMR chemical shift prediction as a filter for determining possible relative stereochemistry

Mikhail E. Elyashberg, Kirill A. Blinov, Antony J. Williams
Published Online: Feb 10 2009 8:59AM

DOI: 10.1002/mrc.2396

The reliable determination of stereocenters contained within chemical structures usually requires utilization of NMR data, chemical derivatization, molecular modeling, quantum-mechanical calculations and, if available, X-ray analysis. In this article we show that the number of stereoisomers which need to be thoroughly verified can be significantly reduced using NMR chemical shift calculations for the full stereoisomer set of possibilities using a fragmental approach based on HOSE codes. The applicability of this suggested method is illustrated using a series of complex chemical structures.

A systematic approach for the generation and verification of structural hypotheses

Mikhail Elyashberg, Kirill Blinov, Antony Williams
Published Online: Feb 5 2009 4:33AM

DOI: 10.1002/mrc.2397

In this article we show that the most rational manner by which to create structural hypotheses is by the application of an expert system capable of deducing all potential structures consistent with the experimental spectral data. Empirical or quantum-mechanical (QM) NMR prediction methods are compared. It is shown that when an expert system is used the best structure(s) can be distinguished using either incremental or neural net (NN)-based NMR prediction algorithms.

Development of a fast and accurate method of 13C NMR chemical shift prediction

Available online 11 February 2009
Kirill A. Blinov, Yegor D. Smurnyy, Tatiana S. Churanova, Mikhail E. Elyashberg, Antony J. Williams

DOI:10.1016/j.chemolab.2009.01.010

In this article we describe a fast and accurate method of 13C NMR chemical shift prediction. The high speed of chemical shift calculation described is achieved using a simple structure description scheme based on individual atoms rather than functional groups. The systematic choice of an appropriate encoding scheme and the usage of partial least squares regression on a large training set has resulted in a robust and fast algorithm. The approach provides accuracy comparable with other well known approaches but demonstrates accelerated calculation speeds of up to a thousand times faster.

I am the proud father of twin 6 year old boys. They are in the middle of a project to get postcards from all US states around the country so I am making a request to those readers of this blog around the country. Would you be so kind as to send a state-specific postcard to our sons at the following addresses…it would be much appreciated! Thanks

 

Franklin Academy 1,

Mrs Rollin’s Kindergarten Class

Attention: Taylor Williams

604 Franklin Street

Wake Forest,

NC-27587

 

and 

 

Franklin Academy 1

Mrs London’s Kindergarten Class

Attention: Tyler Williams

604 Franklin Street

Wake Forest,

NC-27587

An announcement today from the company where I spent 10 years of my career, the last few as their Chief Science Officer.

“Toronto, Canada (February 9, 2009)—Advanced Chemistry Development, Inc., (ACD/Labs) and Pharma Algorithms, Inc., have joined software development and business resources to better serve the extensive Chemical, Environmental, and Pharmaceutical markets, creating a new leader in in silico physicochemical, ADME, Metabolism, and Toxicology screening and prediction.” More here…

I know the experts from both companies who have been developing the physicochemical property prediction software for many years and this combination of knowledge and expertise in this area is going to be hard to beat now. It will be very interesting to watch what the joint efforts will deliver now.

I stole the title for this blog post from American Citizen. Next week I will be sitting at his bedside with his wife after he goes through surgery. What he is going through is life-threatening and could disable him for life if things go awry. His experiences of what he is going through with our Health care system in America are amusing. Because of his wit, intelligence and work experience in the health care industry, his story from this point, through surgery and to recovery will be a fun and enlightening read. In his own words…

“This year, I find myself disabled with degenerative spinal disease and am awaiting surgery on Tuesday February 3rd. Since I have little else to do, I thought I would archive my experiences on this blog and also post some videos of the adventure.

As I write this stuff, keep in mind that I have spent numerous years working for my cause: universal coverage for all Americans and the deployment of a universal personal health record to prevent errors in clinical judgment and facilitate a smooth transition for all patients between systems of care.” read the rest of the blog post here…

Those who frequent the ChemConnector or ChemSpider blogs, or have these plugged into your Readers will have noticed a sudden silence from me in the New year. It was one of those “phone calls you never want” calls. My mother was rushed into hospital with a subarachnoid hemorrhage. That is NOT a bleeding spider deep in her waters (get it? A sub arachnid hemorrhage…) but a bleed in the brain. It is a form of stroke and as Wikipedia so nicely states (scary)  “Up to half of all cases of SAH are fatal and 10–15% die before reaching a hospital”. My mother made it to hospital thanks to the valiant efforts of my sister who had experience of exactly this medical emergency since her friend had SAH just over a year ago. By the time I got home three days later my mother was safely at the Walton Center,supposedly one of the best neurology hospitals in the UK. When I walked onto the ward for the first time after a red eye flight from the US and no sleep for about 30 hours, my mother was awake, but tired. She was bruised from all the lines running into her and had a drain running from her head to a bag draining fluid from the brain to prevent hydrocephalus. they must have been collecting over a half litre of fluid every day or so. Whenever I was there the bag was full of bloody fluid and seemed to get drained regularly. It’s very concerning and emotional for any child to see their parent in such a state….

In the first couple of days she was talkative but sleepy. With SAH it’s the few days following the event that are particularly telling and dangerous. No different in this case. All hell broke loose as she headed down from the normal ward and down to the High Dependency Unit (one nurse, per two patients) one day. We received a call and when we arrived she wasn’t conscious and non-responsive. Within a few days she had declined and had moved to the critical care (1 nurse, 1 patient it seemed) ward as a result of the drain from her head blocking and a build up of fluid, heart arrythmia, low blood pressure and an infection. They made a 6 inch cut across the scalp, drilled a hole into the skull and ran a fresh drain into a ventricle of the brain. The next three days were emotionally and physically draining (3 hours a day of driving and not knowing whether she would be able to talk that day or not or even know who we were. By the time she got back to High Dependency (who would have thought that would seem like a happy day…but after critical care it is!) she was on seven drugs, had mainlines running into her femoral artery and later the carotid artery. She was bruised and bandaged, cabled, wired and clearly in distress. At one point her eyes communicated “Enough…I can’t do this anymore” and it was one of the hardest moments of my life…but a singly defining moment in the nature of my relationship with my sister and my mother…and how closely connected we are.

During that period the doctors performed endovascular surgery to insert a coil as described in detail here. My mother now has Platinum in her brain and without it would likely not survive. The stress on her system would not been conducive to her surviving a more invasive surgery. When I left the UK, after almost 3 weeks, multiple changes to my flights (and lots of charges from United airlines!) my mother was off of all drugs, sitting up, had just drank her first glass of water in 7 days (she was on a nose feed for food for a long time and was receiving intravenous fluids the entire time) . I’ve been home almost a week and she is now eating soups, drinking hot drinks, can get out of bed and is learning to walk again…after three ways in bed there is a lot of muscle atrophy.

And so to the National Health Service of the UK. I have heard MANY nightmare stories and experienced some myself when I lived in the UK. However, I’ve lived in Canada and now live in the US. I have nightmare stories and experiences in both countries. Those stories are for another time… What I can say is that the treatment my mother received was outstanding. Her nurses and doctors were phenomenal. There were not only skilled at their jobs but sympathetic to us at a human level, listened to us when we were concerned and educated us when we asked. The coiling procedure is not available in every hospital and is state of the art surgery. Bottom line is my mother nearly died the moment the hemorrhage happened (50% of people do!) and, in my opinion, she went to the edge and back a number of times in 3 weeks. The medical staff clearly saved her life and I and my family are indebted to them for the treatment and the experience. one concern we didn’t have to deal with is “cost”. Even for the most mundane procedures in the US there is a cost concern. Having visited friends and hospital members in hospital I am conscious of the “how much per pill” mentality that persists here. Based on what I saw happen to my mother, and the 4 weeks of hospital stay to come and months of rehabilitation to follow my mothers treatment and recovery in this country would cost well over a hundred thousand dollars..probably more (maybe some one can give me an inform guess?). In the UK the National Health Service assumes those costs. There is no bill to come that we need to worry about. The focus can be on the patient, their rehabilitation and care. In this country I have sensed and discussed with some close friends the mentality of “what is a life worth?”. What child wants to be put in that situation?!

And so my plea to President Obama. “Please stay on task with your intentions to provide affordable health care for all families. Rich or poor none of us want to be faced with the challenging questions associated with the mentality of “What is a life worth” that will prevail unless health care costs are brought under control in this country. We have research investments in this country which have delivered incredible technologies to preserve life as we are threatened. We have drugs to support and enhance life when burdened by sickness and slowed by age. Yet, for many, basic healthcare remains out of reach. It is past the time for change. The majority of the populace, whether they voted for you or not, will lend their support to you to make the necessary changes. The world is watching and you can lead the change in healthcare. You have my support.”

My best friend is right in the middle of the challenges of “commercialized health care” in the United States. Jeff is a wonderful man and one of my life mentors. He is at once incredibly intelligent, thoughtful, caring, challenging and motivating. He is presently struggling with a health issue of his own and is about to enter into the challenges of dealing with the costs of excellent care, some of the (in)adequacies of the system, and going under the knife for a very scary yet incredible surgery. He has the blog American Citizen and is about to start posting videos about the challenges he is going through. Knowing Jeff they will be witty, amusing and straight to the point. Check out his blog and watch out for the movies.

I was asked to put together a list of publications recently and finally ended up with something that seems an accurate representation of work I’ve been involved with. I’ve been asked many times about my background so post it here for information

Antony Williams Scientific Publications (up to December 5th 2008)

1989

1. F.L. Lee, K.F. Preston, A.J. Williams, L.H. Sutcliffe, A.J. Banister, S.T. Wait^, A single-crystal electron paramagnetic resonance study of the 4-phenyl-1,2,3,5-dithiadiazolyl radical Magn. Reson. Chem. 27, 1161-1165 (1989).

1990

2. D.G. Gillies, S.J. Matthews, L.H. Sutcliffe and A.J. Williams, The Evaluation of Two Correlation Times for Methyl Groups from Carbon-13 Spin-lattice Relaxation Times and nOe Data J. Magn. Reson., 86, 371 (1990)

3. P.J. Bratt, D.G. Gillies, L.H. Sutcliffe and A.J. Williams, NMR Relaxation Studies of Internal Motions - A Comparison between Micelles and Related Systems, J. Phys. Chem., 94(7), 2727 (1990)

4. R.C. Hynes, J.R. Morton, J.A. Hriljac, Y. LePage, K.F. Preston, A.J. Williams, F. Evans, M.C. Grossel and L.H. Sutcliffe, Isolated Free Radical Pairs in Rb+TCNQ- 18-crown-6 Single Crystals, J.Chem. Soc.,Chem. Commun., 5, 439 (1990)

5. P.J. Krusic, J.R. Morton, K.F. Preston, A.J. Williams and F. Lee, EPR Spectrum of the Fe2(CO)8- Radical Trapped in Single Crystals of PPN+HFe2(CO)8- , Organometallics 9, 697 (1990).

6. R. Hynes, K.F. Preston, J.J. Springs, and A.J. Williams, Single-crystal EPR Study of Radical Pairs in [Fe(mesitylene)22+] {C3[C(CN)2]3-}2, J. Chem. Phys. 93(4), 2222, 1990

7. R. Hynes, K.F. Preston, J.J. Springs, and A.J. Williams, EPR Studies of Radical Pairs [M(CO)5]2 (M = Cr, Mo, W) Trapped in Single Crystals of PPN+ HM(CO)5-, Organometallics, 9, 2298 (1990)

8. R. Hynes, K.F. Preston, J.J. Springs, and A.J. Williams, Electron paramagnetic resonance study of the tetracarbonyl(trimethylphosphite)tungstate(1-) radical anion trapped in a single crystal of [N(PPh3)2][W(CO)4H{P(OMe)3}], Journal of the Chemical Society, Dalton Transactions: Inorganic Chemistry (1972-1999) 12, 3655-61(1990)

1991

9. R. Hynes, K.F. Preston, J.J. Springs, J. Tse and A.J. Williams, EPR Studies of M(CO)5- Radicals (M = Cr, Mo, W) Trapped in Single Crystals of PPh4+ HM(CO)5- , J. Chem. Soc. Faraday Trans., 87(19), 3121 (1991)

10. R.C. Hynes, J.R. Morton, K.F. Preston, A.J. Williams, F. Evans, M.C. Grossel, L.H. Sutcliffe, and S.C. Weston, An EPR Study of Isolated Free Radical Pairs in M+ 18-Crown-6 TCNQ- salts (TCNQ:7,7,8,8-tetracyanoquinodimethane; M=K, Rb), J. Chem. Soc. Faraday Trans., 87(14), 2229 (1991)

11. L.M. Bull, D.G. Gillies, S.J. Matthews, L.H. Sutcliffe, and A.J. Williams, Carbon-13 NMR Relaxation Study of the Overall and Internal Motions in Compounds Containing n-Octyl Chains, Magn. Reson. Chem., 29, 273 (1991)

12. K.F. Preston, J.J. Springs, and A.J. Williams, The EPR Spectrum of (C5Me5)MoCl2(PMe3) in Solution and Trapped in Single Crystals of (C5Me5)MoCl(PMe3)(N2), Inorg. Chem., 30, 113 (1991)

13. J.H. MacNeil, A.C. Chiverton, S. Fortier, M.C. Baird, R.C. Hynes, A.J. Williams, K.F. Preston and T. Ziegler, An X-ray Crystallographic and Single-Crystal EPR Investigation of the Cationic, Iron-Centred Radical Tricarbonylbis(triphenylphosphine)iron(I). A Theoretical Examination of the Structural Preferences of Five-Coordinated Seventeen-Electron Complexes, J. Am. Chem. Soc., 113, 9834 (1991)

14. R. Hynes, K.F. Preston, J.J. Springs, and A.J. Williams, EPR studies of chromium tungsten carbonyl sulfur dimer, S[M(CO)5]2-, radicals (M = chromium, tungsten) trapped in single crystals of bis(triphenylphosphino)imium salt, PPN+HS[M(CO)5]2-, Organometallics, 10, 180-5 (1991)

15. R. Hynes, K.F. Preston, J.J. Springs, and A.J. Williams, X-Ray Crystallographic, Single-Crystal EPR, and Theoretical Study of Metal-Centred Radicals of the Type {C5R5Cr(CO)2L} (R=H,Me; L=CO, Tertiary Phosphine), J. Am. Chem. Soc., 113, 542 (1991)

16. R. Hynes, K.F. Preston, J.J. Springs, and A.J. Williams, EPR Spectra in gamma-irradiated PPN+ HFeW(CO)9- Crystals, Magn. Reson. Chem., 29, 476 (1991)

17. R. Roy, F.D. Tropper and A.J. Williams, 1H and 13C Chemical Shift Assignments of Para-Substituted O-aryl b-D-N-acetyl glucopyranosides, Magn. Reson. Chem., 29, 852 (1991)

18. R. Duchateau, A.J. Williams, S. Gambarotta and M.Y.Chiang, Carbon-Carbon Double-Bond Formation in the Intermolecular Acetonitrile Reductive Coupling Promoted by a Mononuclear Titanium (II) Compound. Preparation and Characterization of Two Titanium (IV) Imido Derivatives, Inorg. Chem. 30, 4863 (1991)

1992

19. J. Milne and A.J. Williams, Exchange Processes in Diselenium and Selenium-sulphur Dihalides, Se2X2, SeSX2 (X = Br, Cl). A 77Se 2D-EXSY Study, Inorg. Chem., 31, 4534 (1992)

20. L.A. Denys, A.J. Williams and G. Sachs, 2D Hetero- and Homonuclear NMR Study of a K+ Competitive Fluorescent Inhibitor of the H,K-ATPase, Bull. Magn. Reson., 15, 89 (1992)

21. J-C. Bradley, T. Durst, and A. J. Williams, Thermolysis of 2-Benzylidenebenzocyclobutenols, J. Org. Chem., 57, 6575 (1992)

1993

22. R. Roy, F.D. Tropper, A.J. Williams and J.R. Brisson, Global and Internal Molecular Dynamics of Poly(acrylamide-co-allyl 2-acetamido-2-deoxy-D-glucopyranosides) Glycopolymers from 13C NMR Relaxation Studies, Can. J. Chem., 71, 12 (1993)

1994

23. A.J. Williams and J.-C. Bradley, Analysis of the C13 and H1 Spectra of Mixtures of Benzylidene Derivatives, Magn. Reson. Chem. 32, 496 (1994)

24. B. Antalek, S.Song, L. Oppeheimer, A.J. Williams, E. Garcia and J. Texter, Cosurfactant-Induced Electron Transfer in Highly Resistive Microemulsions, Langmuir, 9, 2782 (1994)

25. D.D. Miller, W. Lenhart, B. Antalek, A.J. Williams and M.J. Hewitt, The Use of NMR to Study Sodium Dodecyl Sulfate-Gelatin Interactions, Langmuir, 10, 68 (1994)

26. B. Antalek, A.J. Williams, E. Garcia and J. Texter, NMR Analysis of Interfacial Structure Transitions Accompanying Electron Transfer Threshold Transitions in Reverse Microemulsions, Langmuir, 10, 4459, (1994)

1995

27. R. Hynes, P.J. Krusic, K.F. Preston, J.J. Springs, A.J. Williams and J.S. Miller, Single Crystal EPR Study of Triplet Excitons in Tetraethylammonium 2,3,5,6 Tetracyano-p-benzoquinone. Evidence for an Interdimer Triplet Exciton, JACS, 117, 2547 (1995)

28. M.R. Detty, D. Young and A.J. Williams, A Mechanism for Heteroatom Scrambling in the Synthesis of Unsymmetrical Chalcogenpyrilium Trimethine Dyes, J. Org. Chem. 60, 6631 (1995)

29. R. Roy, F. Tropper and A.J. Williams, Substituent-induced chemical shifts of aromatic carbon centers in a series of non-acetylated and peracetylated para-substituted aryl 2-N-acetamido-2-deoxy-b-D-glucopyranosides, Magnetic Resonance in Chemistry 33, 981 (1995)

30. M.R. Detty, M.J. Hewitt, A.J. Williams and M. McMillan, H-1 NMR Exchange Reactions in Te(IV) Derivatives with Cleavage of Te-N Bonds, Organometallics 14, 5258 (1995)

1996

31. R.Lok, R. Leone and A.J. Williams, Facile Rearrangements of Alkynylamino Heterocycles with Noble Metal Cations, Journal of Organic Chemistry 61(10), 3289 (1996)

32. B. Antalek, A.J. Williams and J. Texter, Self-diffusion near the percolation threshold in reverse microemulsions, Phys Rev. E. 54 (6), 5913 (1996)

1997

33. B. Antalek, A.J. Williams, J. Texter, J. Feldman, G. Yuri and N. Garti, Microstructure Analysis at the Percolation Threshold in Reverse Microemulsions, Colloids and Surfaces A: Physicochemical and Engineering Aspects 128, 1 (1997)

34. B. Antalek, A.J. Williams and J. Texter, Observation of a Reverse Micelle to Sponge Phase Transition, J. Chem. Phys. 106, 7869-7872 (1997)

35. D.E. Brown, A.J. Williams and D. McLaughlin, WIMS - A Web-based Information Management System, Trends in Analytical Chemistry, 16, 370 (1997)

1998

36. A.J. Williams, Combining Sample, Structural, and Spectral Information in an Information Management System, Sci. Comput. Auto. 15, 60 (1998).

37. M. Foster, E. Kolovanov, S. Mabury, A. Marsella and A.J. Williams, Log P, partition coefficients of selected benzoylphenylurea insecticides, EnviroAnalysis 731 (1998)

1999

38. A.J. Williams and A. Yerin, The Need for Systematic Naming Software Tools for Exchange of Chemical Information, Molecules, 9, 255 (1999)

2000

39. M.E. Elyashberg, K.A. Blinov and A.J. Williams, Computer-aided Molecular Structure Elucidation on the Basis of 1D and 2D NMR Spectra, Applied Magnetic Resonance, (May 2000)

40. A.J. Williams, Recent Advances in NMR Prediction and Automated Structure Elucidation Software, Current Opinion in Drug Discovery & Development 3, 298 (2000)

41. A.J. Williams and S.G. Golotvin, Improved baseline correction and modeling of FT NMR spectra, J. Magn. Reson, 146, 122 (2000)

2001

42. K.A. Blinov, M.E. Elyashberg, S.G. Molodtsov, A.J. Williams and E.R. Martirosian, An Expert System for Automated Structure Elucidation Utilizing ¹H-¹H, ¹³C-¹H, and ¹⁵N-¹H 2D NMR correlations, Fresenius J. Anal. Chem., 369, 709 (2001)

43. A.J. Williams, V. Lashin and M. Lee, An integrated desktop mass spectrometry processing and molecular structure management system, Spectroscopy 16, 38 (2001)

2002

44. G.E. Martin, C.E. Hadden, D.J. Russell, B.D. Kaluzny, J.E. Guido, W.K. Duholke, B.A. Stiemsma, T.J. Thamann, R.C. Crouch, K.A. Blinov, M.E. Elyashberg, E.R. Martirosian, S.G. Molodtsov, A.J. Williams, P.L. Schiff, Jr., Identification of Degradants of a Complex Alkaloid Using NMR Cryoprobe Technology and ACD/Structure Elucidator, J. Heterocyclic Chem. 39, 1241 (2002)

45. M.E. Elyashberg, K.A. Blinov, A.J. Williams, E.R. Martirosian, S.G. Molodtsov, Application of a New Expert System for the Structure Elucidation of Natural Products from the 1D and 2D NMR Data, J. Nat. Prod., 65, 693 (2002)

46. S. Golotvin and A.J. Williams, A new approach to automated first-order multiplet analysis. Magn Reson Chem. 40, 331 (2002)

47. G . E. Martin, C .E. Hadden, D. J. Russell, B. D. Kaluzny, J. E. Guido, W. K. Duholke, B. A. Stiemsma, T. J. Thamann, R. C. Crouch, K. A. Blinov, M. E. Elyashberg, E. R. Martirosian, S. G. Molodotsov, A. J. Williams, and P. L. Schiff, Jr., Identification of Degradants of a Complex Alkaloid Using NMR Cryoprobe Technology and ACD/Structure Elucidator, J. Heterocyclic Chem., 39 1241-1250 (2002).

2003

48. D. G. Gillies, L. H. Sutcliffe and A. J. Williams, Variable-temperature high-pressure investigation of the cobalt-59 NMR spectroscopy of aqueous potassium hexacyanocobaltate (III) Magn Reson Chem. 40, 57 (2002)

49. A. J. Williams. Applications of Computer Software for the Interpretation and Management of Mass Spectrometry Data in Pharmaceutical Science, Current Topics in Medicinal Chemistry, 2, 99 (2002)

2003

50. K. A. Blinov, D. Carlson, M. E. Elyashberg, G. E. Martin, E. R. Martirosian, S. Molodtsov, and A. J. Williams, Computer-Assisted Structure Elucidation of Natural Products with Limited 2D NMR Data: Applications of the StrucEluc System, Magn. Reson. Chem., 41, 359-372 (2003).

51. G. E. Martin, D. J. Russell, K. A. Blinov, M. E. Elyashberg and A. J. Williams, Applications and Advances in Cryogenic NMR Probes & Computer-Assisted Structure Elucidation. Ann. Magn. Reson., 2, 1-31 (2003)

52. A.J. Williams. Recent Advances in NMR Prediction and Automated Structure Elucidation Software. Current Opinion in Drug Discovery & Development, 3, 298 (2003)

53. K. Blinov, M. Elyashberg, E. R. Martirosian, S. G. Molodtsov, A. J. Williams, M. H. M. Sharaf, P. L. Schiff, Jr., R. C. Crouch, G. E. Martin, C. E. Hadden, and J. E. Guido, “Quindolinocryptotackieine: The Elucidation of a Novel Indoloquinoline Alkaloid Structure through the Use of Computer-Assisted Structure Elucidation and 2D-NMR,” Magn. Reson. Chem., 41, 577-584 (2003).

54. M. E. Elyashberg, K. A. Blinov, E. R. Martirosian, S. G. Molodtsov, A. J. Williams, and G. E. Martin, Automated Structure Elucidation – The Benefits of a Symbiotic Relationship between the Spectroscopist and the Expert System, J. Heterocyclic Chem., 40, 1017-1029 (2003).

2004

55. M. E. Elyashberg, K. A. Blinov, A. J. Williams, S. G. Molodtsov, G. E. Martin, and E. R. Martirosian, Structure Elucidator: A Versatile Expert System for Molecular Structure Elucidation from 1D and 2D NMR Data and Molecular Fragments, J. Chem. Inf. Comput. Sci. 44, 771-792 (2004).

56. A. J. Simpson, B. Lefebvre, A. Moser, A.J. Williams, N. Larin, M. Kvasha, W. L. Kingery and B. Kelleher. Identifying residues in natural organic matter through spectral prediction & 2D NMR datasets. Magn. Reson. Chem. 42, 14 (2004)

57. S. G. Molodtsov, M. E. Elyashberg, K. A. Blinov, A. J. Williams, E. E. Martirosian, G. E. Martin, and B. Lefebvre. Structure Elucidation from 2D NMR Spectra Using the StrucEluc Expert System: Detection and Removal of Contradictions in the Data. J. Chem. Inf. Comp. Sci., 44, 1737-1751 (2004)

58. G. J. Sharman, I. C. Jones, M. P. Parnell, M. C. Willis, M. F. Mahon, D. V. Carlson, A. J. Williams, M. E. Elyashberg, K. A. Blinov, S. G. Molodtsov. Automated structure elucidation of two products in a reaction of an a,b -unsaturated pyruvate. Magn. Reson. Chem. 42, 567 (2004)

59. J. Meiler, B. Lefebvre, A.J Williams and M. Hachey. Using neural networks for 13C NMR chemical shift prediction-comparison with traditional methods. J. Magn. Reson. 171, 1 (2004)

2005

60. Y. D. Smurnyy, M. E. Elyashberg, K. A. Blinov, B. A. Lefebvre, G. E. Martin, and A. J. Williams, Computer-Aided Determination of Relative Stereochemistry and 3D Models of Complex Organic Molecules from 2D NMR Spectra, Tetrahedron, 61, 9980-9989 (2005).

61. K. A. Blinov, N. I. Larin, M. P. Kvasha, A. Moser, A. J. Williams, and G. E. Martin, Analysis and Elimination of Artifacts in Indirect Covariance NMR Spectra via Unsymmetrical Processing, Magn. Reson. Chem., 43, 999 (2005).

2006

62. K. A. Blinov, N. I. Larin, A. J. Williams, K. A. Mills, and G. E. Martin, Unsymmetrical Covariance Processing of COSY or TOCSY and HSQC NMR Data to Obtain the Equivalent of HSQC-COSY and HSQC-TOCSY Spectra, J. Heterocyclic Chem., 43, 145-147 (2006).

63. S. S. Golotvin, E. Vodopianov, B. A. Lefebvre, A. J. Williams, and T. D. Spitzer. Automated structure verification based on 1H NMR prediction. Magn. Reson. Chem., 44, 524 (2006)

64. K. A. Blinov, N. I. Larin, A. J. Williams, M. Zell, and G. E. Martin, Long-Range Carbon-Carbon Connectivity via Unsymmetrical Indirect Covariance Processing of HSQC and HMBC NMR Data, Magn. Reson. Chem., 44, 143-147 (2006).

65. A.J. Simpson, B. Lam, M.L. Diamond, D.J. Donaldson, B. Lefebvre, A. Moser, A.J. Williams, N. Larin and M. Kvasha. Assessing the organic composition of urban surface films using nuclear magnetic resonance spectroscopy. Chemosphere, 63, 142 (2006)

66. M. E. Elyashberg, K. A. Blinov, A. J. Williams, S. G. Molodtsov, and G. E. Martin, Are Deterministic Expert Systems for Computer-Assisted Structure Elucidation Obsolete? J. Chem. Inf. Model. 46, 1643-1656 (2006).

67. A. J. Simpson, W. L. Kingery, B. Lefebvre, A. Moser, A.J. Williams, M. Kvasha and B.P. K8elleher. The application of 1H high-resolution magic-angle spinning NMR for the study of clay-organic associations in natural and synthetic complexes. Langmuir 22, 4498 (2006)

68. G. M. Rishton, K. LaBonte, A. J. Williams, K. Kassam and E. Kolovanov. Computational approaches to the prediction of blood-brain barrier permeability: a comparative analysis of central nervous system drugs versus secretase inhibitors for Alzheimer’s disease Current Opinion in Drug Discovery & Development, 9, 303 (2006)

2007

69. K. A. Blinov, A. J. Williams, B. D. Hilton, P. A. Irish, and G. E. Martin, The Use of Unsymmetrical Indirect Covariance NMR Methods to Obtain the Equivalent of HSQC-NOESY Data, Magn. Reson. Chem., 45, 544-546 (2007). 10.1002/mrc.1998

70. M. E. Elyashberg, K. A. Blinov, S. G. Molodtsov, A. J. Williams, and G. E. Martin, Fuzzy Structure Generation: An Efficient New Tool for Computer-Aided Structure Elucidation (CASE), J. Chem. Inf. Model., 47, 1053-1066 (2007). 10.1021/ci600528g

71. G. E. Martin, P. A. Irish, B. D. Hilton, K. A. Blinov, and A. J. Williams, Utilizing Unsymmetrical Indirect Covariance Processing to Define ¹⁵N-¹³C Connectivity Networks, Magn. Reson. Chem., 45, 624-627 (2007). 10.1002/mrc.2029

72. G. E. Martin, B. D. Hilton, P. A. Irish, K. A. Blinov, and A. J. Williams, Application of Unsymmetrical Indirect Covariance NMR Methods to the Computation of ¹³C-¹⁵N HSQC-IMPEACH and ¹³C-¹⁵N HMBC-IMPEACH Correlation Spectra of the Alkaloid Vincamine, Magn. Reson. Chem., 45, 883-888 (2007).

73. G. E. Martin, B. D. Hilton, P. A. Irish, K. A. Blinov, and A. J. Williams, ¹³C-¹⁵N Connectivity Networks via Unsymmetrical Indirect Covariance Processing of ¹H-¹³C HSQC and ¹H-¹⁵N IMPEACH Spectra, J. Heterocyclic Chem., 44, 1219-1222 (2007).

74. G. E. Martin, B. D. Hilton, P. A. Irish, K. A. Blinov, and A. J. Williams, Using Unsymmetrical Indirect Covariance Processing to Calculate GHSQC-COSY Spectra, J. Nat. Prod., 70, 1393-1396 (2007). 10.1021/np070221j

75. G. E. Martin, B. D. Hilton, K. A. Blinov, and A. J. Williams, ¹³C-¹⁵N Correlation via Unsymmetrical Indirect Covariance NMR: Application to Vinblastine, J. Nat. Prod., 2007, 70, 1966-1970 10.1021/np070361t

76. S. S. Golotvin, E. Vodopianov, R. Pol, B. A. Lefebvre, A. J. Williams, R. D. Rutkowske and T. D. Spitzer, Automated structure verification based on a combination of 1D 1H NMR and 2D 1H–13C HSQC spectra, Magn. Reson. Chem. 2007, 45, 803–813

77. G. E. Martin, B. D. Hilton, K. A. Blinov, and A. J. Williams, Long-Range Homonuclear Couplings via Covariance Processing of GCOSY Spectra, Magn. Reson. Chem., submitted (2007).

78. M. E. Elyashberg, A. J. Williams, and G. E. Martin. Computer-Assisted Structure Verification and Elucidation Tools In NMR-Based Structure Elucidation. Review article. Progress in NMR Spectroscopy (2007) 10.1016/j.pnmrs.2007.04.003

79. B. Lam, A. Baer, M. Alaee, B. Lefebvre, A. Moser, A. J. Williams, and A. J. Simpson. Major Structural Components in Freshwater Dissolved Organic Matter, Environ. Sci. Technol., 41 (24), 8240–8247 (2007) 10.1021/es0713072

80. K. A. Blinov, C. Steinbeck, M. E. Elyashberg, and A. J. Williams, The Performance Validation of Neural Network Based ¹³C NMR Prediction Using a Publicly Available Data Source, J. Chem. Inf. Model., 48 (3), 550 -555, 2008. 10.1021/ci700363r

2008

81. Y. D. Smurnyy, K. A. Blinov, T. S. Churanova, M. E. Elyashberg, and A. J. Williams. Toward More Reliable ¹³C and ¹H Chemical Shift Prediction: A Systematic Comparison of Neural-Network and Least-Squares Regression Based Approaches, J. Chem. Inf. Model. 48, 128-134, 2008

82. A.J. Williams, A perspective of Publicly Accessible/Open Access Chemistry Databases, Drug Discovery Today, 13(11/12), 502-506, 2008

83. A.J. Williams, Internet-based tools for communication and collaboration in chemistry, Drug Discovery Today, 13(11/12), 495-501, 2008

84. A.J. Williams, Public Chemical Compound Databases, Current Opinions in Drug Discovery, 11(3), 393-404, 2008

85. M. E. Elyashberg, K. A. Blinov, S. G. Molodtsov, E. D. Smurny, A.J. Williams and T.S. Churanova, Progress in Qualitative Chemometrics: Computer-Assisted Methods for Molecular Structure Elucidation. Submitted to J. Chemometrics.

86. Y. D. Smurnyy, K. A. Blinov, T. S. Churanova, M. E. Elyashberg, and A. J. Williams. Development of a fast and accurate method of ¹³C NMR chemical shift prediction. Submitted to J. Chemometrics.

87. J.C. Bradley, K. Owens and A.J Williams, Chemistry Crowdsourcing and Open Notebook Science, Nature Precedings : doi:10.1038/npre.2008.1505.1 (2008)

88. J.C Bradley, K. Mirza, K. Owens, T. Osborne and A.J. Williams, Optimization of the Ugi reaction using parallel synthesis and automated liquid handling, Nature Precedings : hdl:10101/npre.2008.2237.1 (2008)

89. G. E. Martin, B. D. Hilton, K. A. Blinov, and A. J. Williams, Using Indirect Covariance Spectra to Identify Artifact Responses in Unsymmetrical Indirect Covariance Calculated Spectra, Magn. Reson. Chem., 46, 138-143 (2008).

90. M. E. Elyashberg, A. J. Williams, D. C. Lankin, G. E. Martin, J. Porco, W. F. Reynolds, and C. Singleton, Applying Computer-Assisted Structure Elucidation Algorithms for the Purpose of Structure Validation – Revising the NMR Assignments of Hexacyclinol, J. Nat. Prod., 71, 581-588 (2008).

91. G. E. Martin, B. D. Hilton, K. A. Blinov, and A. J. Williams, Unsymmetrical indirect covariance processing of hyphenated and long-range heteronuclear 2D NMR spectra - enhanced visualization of 2JCH and 4JCH correlation responses. J. Heterocyclic Chem., 45, 1109-1113 (2008).

92. G. E. Martin, B. D. Hilton, K. A. Blinov, and A. J. Williams, Multistep correlations via covariance processing of COSY/GCOSY spectra: opportunities and artifacts. Magn. Reson. Chem. 46, 997-1002, (2008).

93. M.E. Elyashberg, K.A. Blinov and A.J. Williams, A Systematic Approach for the Generation and Verification of Structural Hypotheses. Accepted for Publication in Magn. Reson. Chem..

94. M. E. Elyashberg, A. J. Williams, and K.A. Blinov, The Application of Empirical Methods of ¹³C NMR Chemical Shift Prediction as a Filter for Determining Possible Relative Stereochemistry. Accepted for Publication to Magn. Reson. Chem.

95. G. E. Martin, B. D. Hilton, K. A. Blinov, and A. J. Williams, Modulation effects in GHSQC-COSY Spectra Calculated Using Unsymmetrical Indirect Covariance Processing Methods, manuscript in preparation (2008).

PUBLISHED PAPERS AND OTHER MATERIALS (Unrefereed)

1. A.J. Williams and B. Antalek, 900G/cm Self Diffusion Measurements in a Narrow Bore 500 MHz NMR Spectrometer, TAMU NMR Newsletter, 434 (1994)

2. A.J. Williams, Management of Spectroscopy-Based LIMS Information, LIMS/Letter 4(3), p. 14, (1998).

3. A.J. Williams, Web-Based LIMS Systems for Analytical R & D Laboratories, Scientific Computing World (May 1998)

4. A.J. Williams, JCAMP : The continuing saga of a “Standard” File Format for NMR, NMR Newsletter (May 1998)

5. A.J. Williams, Shift Assignment Errors in the Published Literature - the Impact on Computational Shift Prediction, NMR Newsletter 485, (1999)

6. A.J. Williams, Industry Insight - The Need for Systematic Naming, Sci. Computing and Automation, (September 1999)

7. A.J. Williams and D. McLaughlin, Spectroscopy management needs as part of an analytical laboratory information management system, Spectroscopy 14, 38 (1999)

8. A.J. Williams and V. Kulkov, A corporate solution for structure-based chromatography and spectroscopy management, Editor(s): Collier, Harry. Proceedings of the International Chemical Information Conference, Annecy, France, Oct. 25-28, 1999, 113-118. Publisher: Infonortics Ltd., Tetbury, UK

9. A.J. Williams , Integrated Molecular Structure and Chromatography Management, Scientific Computing and Instrumentation (August 2000)

10. A.J. Williams and H. Hoffmann, Massenspektren und Strukturen: Schnelle Hilfe gegen Kopfzerbrechen!, The GDCh, “Blaue Blätter” magazine, Germany (September, 2000)

11. A.J. Williams, E. Kolovanov and H. Hoffmann, ACD/ChromManager:Ein Chromatographie-Daten-System mit Molekulstruktur-Management
The GIT magazine, Germany, Austria and Switzerland, (February, 2000)

12. A.J. Williams, Offline Processing of Bruker Digitally Filtered NMR Data, NMR Newsletter, (February 2000)

13. A.J. Williams and S.G. Golotvin, Automated First-Order Multiplet Analysis, The NMR Newsletter, (December 2000)

14. A.J. Williams and E. Kolovanov, A chromatography data system with integrated molecular structure management, American Laboratory, 32, 22 (2000)

15. A.J. Williams and S.G. Golotvin, Advances in Baseline Correction Applications to Metabonomics Data, The NMR Newsletter, (December 2000)

16. A.J. Williams, ChemSpider and Its Expanding Web Builds a Structure Centric Community for Chemists, Chemistry International, IUPAC

Book Chapters

1. Interfacial Packing Transition of AOT in Reverse Microemulsions, Dynamic Properties of Interfaces & Association Structures, 183-195, D.O. Shah, Ed.AOCS Press,Champaign, IL (1996)

2. Long-range 1H-15N heteronuclear shift correlation, Annual Reports on NMR Spectroscopy 55, 1 (2005), G.E. Martin and A.J. Williams

3. Software for interactive curve resolution using SIMPLISMA. Progress in Chemometrics Research, Chapter 10, 119-135 (2005) Publ: Nova Science Publishers, Inc., Hauppauge, N. Y.

4. The ACS Style Guide: Effective Communication of Scientific Information (An American Chemical Society Publication) by Anne M. Coghill and Lorrin R. Garson, Chapter 17, Chemical Structures (2006), A.J. Williams

5. Applications of 15N NMR spectroscopy in alkaloid chemistry, G.E. Martin, A.J. Williams and M. Solntseva, Editor(s): Fattorusso, Ernesto; Taglialatela-Scafati, Orazio. Modern Alkaloids, (2008), 409-471. Publisher: Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim, Germany

6. Utilizing Long-Range ¹H-¹⁵N 2D NMR Spectroscopy in Chemical Structure Elucidation, Encyclopedia of NMR Spectroscopy, Wiley (2008), G.E. Martin and A.J. Williams

7. Automated Identification and Conversion of Chemical Names to Structure Searchable Information, A.J. Williams and A. Yerin, Chemical Information Mining: Facilitating Literature-Based Discovery, (2008), ISBN-10:1420076493

8. Fundamentals of Spectroscopy: LIMS (Laboratory Information Management Systems), A.J. Williams, Encyclopedia of Spectroscopy & Spectrometry, 2nd Ed, Elsevier (2009), Submitted for Publication

A new publication for which I am a co-author is out on the application of covariance NMR processing…

Multistep correlations via covariance processing of COSY/GCOSY spectra: opportunities and artifacts

 

 Long-range homonuclear coupling pathways can be observed in COSY or GCOSY spectra by the acquisition of spectra with larger numbers of increments of the evolution period, t₁, than would normally be used. Alternatively, covariance processing of COSY-type spectra acquired with modest numbers of t₁ increments, allows the observation of multistage correlations. In this work results obtained from covariance-processed GCOSY spectra are fully analyzed and compared to normally processed COSY and 80 ms TOCSY spectra.

An interesting article regarding the world’s fastest computer was in C&E News today when it hit my desktop. At a time where there is so much focus on High Performance Computing it was interesting to read about the RoadRunner system delivered by IBM to the Los Alamos National Laboratory.

Quoting Wikipedia “Roadrunner differs from many contemporary supercomputers in that it is a hybrid system, using two different processor architectures for the heavy lifting. Usually supercomputers only use one, since it would be easier to design and program for. To tap the full potential of Roadrunner, all software will have to be written specially for this hybrid architecture which is uniquely complex. The hybrid design consists of dual-core Opteron server processors manufactured by AMD utilizing the standard x86 architecture. Attached to each Opteron core is a Cell processor manufactured by IBM using Power Architecture technology. ”

I have blogged previously about Cell Processors being applied for Virtual Screening/Docking (1,2) and have been helping SimBioSys in their marketing and business development of their eHITS Lightning software as discussed here.

With the fastest computer in the world using the Cell processor as part of its architecture, and with the processor now proving itself for docking, the question is whether we will see this processor become even more mainstream in the foreseeable future. It’s NOT easy to port…but it can be done.