Gary E. Martin

Last updated
Gary Martin
Born
Wilkinsburg, Pennsylvania, United States
NationalityAmerican
Alma mater University of Kentucky
University of Pittsburgh
Known for NMR Spectroscopy
Medicinal Chemistry
Scientific career
Fields Chemistry
Spectroscopy
Medicinal Chemistry
Institutions Merck Research Laboratories
Doctoral advisor George A. Digenis

Gary Martin is an American chemist and expert in the fields of both NMR spectroscopy and medicinal chemistry. He is a distinguished fellow at the Merck Research Laboratories. He is also a photographer specializing in the capture of images of lighthouses, especially under conditions of extreme weather. [1] [2]

Contents

Career

Martin holds a B.S. in Pharmacy from the University of Pittsburgh and a Ph.D. degree in Medicinal Chemistry/Pharmaceutical Sciences from the University of Kentucky. [3] He was a Professor of Medicinal Chemistry at the University of Houston from 1975–1989 and the director of the University of Houston NMR Facility between 1984–1989. He moved to the pharmaceutical industry in 1989 and worked at a number of pharmaceutical companies as described below. He has published more than 275 papers, invited reviews, and chapters and is a frequently invited lecturer at national and international NMR meetings.

Between 1989 and 1995 he worked at Burroughs Wellcome (later GlaxoSmithKline) (see reference 3) and worked on the development of new one- and two-dimensional NMR experiments for the solution of complex structural and spectral assignment problems. He developed new methods for the acquisition of submicromole and sub-nanomole NMR data for molecular structure characterization, especially work involving inverse-detected heteronuclear shift correlation techniques. These efforts led to collaborative development with Nalorac Cryogenics Corp. to develop micro inverse detection probes which facilitated the acquisition of HMQC spectra on samples to the level of 0.05 µmole for small (200-500 Da) molecule NMR. [4]

He moved to the Pharmacia corporation between 1996–2003 and ran the Rapid Structure Characterization Group. When Pharmacia was acquired by Pfizer, he served as the senior scientific consultant working on new methods development. He led the development of applications of unsymmetrical indirect covariance NMR, initially in an effort to eliminate artifacts and subsequently in the investigation of the mathematical combination of discretely-acquired 2D NMR data. The time savings for the latter was nearly a factor of 16 in time, with a 10-fold improvement in signal-to-noise ratios vs. directly acquiring an HSQC-TOCSY data set with the same sample. He conducted preliminary investigations into the utilization of indirect covariance NMR spectroscopy as an alternative means of evaluating NMR data for structure characterization and Computer-Assisted Structure Elucidation. He collaborated with a team of scientists at Advanced Chemistry Development, ACD/Labs, led by Antony John Williams, investigating the development of computational methods for automated structure verification and structure elucidation. [5] [6] [7] He developed “accordion-optimized” long-range heteronuclear shift correlation methods to provide experimental access to small long-range heteronuclear couplings for the characterization of proton-“deficient” molecular structures, [8] to experimentally access 4J heteronuclear couplings, to differentiate two-bond from three-bond long-range couplings to protonated carbons, to measure long-range heteronuclear couplings and to provide a reliable means of observing long-range proton-nitrogen correlations without concern for the variability of long-range proton nitrogen coupling constants. [9]

He also collaborated on the development of a new generation of sub-micro inverse detection probes with Nalorac Cryogenics Corporation designed to allow heteronuclear shift correlation experiments to be performed at levels down to 0.01 µmole for small molecules. The collaboration extended to a new generation of cold metal (at temperatures of 8K) 3 mm micro inverse detection probes. In 2006 he joined Schering-Plough and was responsible for the chemical structure characterization of impurities and degradants of candidate drug molecules in support of chemical process research. Schering Plough was acquired by Merck Research Laboratories in 2009. During his time at Merck he has continued to explore the limits of detection for low level samples by heteronuclear 2D NMR using newly developed 1.7 mm Micro CryoProbe™ technology. He has developed, in collaboration with ACD/Labs, and Bruker, unsymmetrical indirect covariance NMR spectroscopy, [10] [11] [12] exploring the calculation of hyphenated heteronuclear 2D correlation spectra. He has also continued collaborative investigations in the area of Computer-Assisted Structure Elucidation (CASE) with ACD/Labs. He has also explored the use of unsymmetrical indirect covariance NMR processing methods to define 13C-15N and 13C-13C heteronuclear connectivity networks.

He was named a 2016 Distinguished Graduate Alumnus of the University of Kentucky College of Pharmacy [13] He was the 2016 recipient of the James N. Shoolery Award to recognize individual contributions in the field of small molecule NMR [14] He was awarded the 2016 EAS Award for Outstanding Achievements in NMR. [15]

Research interests

His ongoing research interests have centered on the development of new NMR methods for the characterization of impurities and degradants of pharmaceuticals focusing on the exploration of new NMR probe technologies for the characterization of extremely small samples using heteronuclear 2D-NMR methods. His interests in this area were pivotal in the development of 3 mm and 1.7 mm probe technologies and he was also an early proponent of cryogenic probe capabilities., [16] [17]

He has had a long-standing interest in heteronuclear NMR and 2D long-range heteronuclear shift correlation in particular. He was among the first to exploit natural abundance long-range 1H-15N heteronuclear shift correlation experiments, those early reports leading to hundreds of published reports that are the subject of multiple reviews and chapters., [18] [19] More recently, his research interests have also led to the development of unsymmetrical indirect covariance NMR processing methods that have the potential for significant spectrometer time savings when experimental access to hyphenated 2D NMR. These methods also provide access to 13C-15N Heteronuclear Single Quantum Coherence-Heteronuclear Multiple Bond Coherence (HSQC-HMBC) correlation data that are experimentally inaccessible at natural abundance, and to HSQC-ADEQUATE correlation plots that allow carbon-carbon connectivity networks of molecules to be mapped without having to resort to the highly insensitive 13C-13C INADEQUATE experiment. In recent years Martin has extended his work into the application of residual dipolar couplings, residual chemical shift anisotropy and DFT calculations to demonstrate that, in combination, some of the most complex chemical structures could be elucidated and making unambiguous assignment essentially difficult or impossible. [20]

Related Research Articles

In nuclear magnetic resonance (NMR) spectroscopy, the chemical shift is the resonant frequency of an atomic nucleus relative to a standard in a magnetic field. Often the position and number of chemical shifts are diagnostic of the structure of a molecule. Chemical shifts are also used to describe signals in other forms of spectroscopy such as photoemission spectroscopy.

<span class="mw-page-title-main">Nuclear magnetic resonance spectroscopy</span> Laboratory technique

Nuclear magnetic resonance spectroscopy, most commonly known as NMR spectroscopy or magnetic resonance spectroscopy (MRS), is a spectroscopic technique to observe local magnetic fields around atomic nuclei. The sample is placed in a magnetic field and the NMR signal is produced by excitation of the nuclei sample with radio waves into nuclear magnetic resonance, which is detected with sensitive radio receivers. The intramolecular magnetic field around an atom in a molecule changes the resonance frequency, thus giving access to details of the electronic structure of a molecule and its individual functional groups. As the fields are unique or highly characteristic to individual compounds, in modern organic chemistry practice, NMR spectroscopy is the definitive method to identify monomolecular organic compounds.

<span class="mw-page-title-main">Solid-state nuclear magnetic resonance</span>

Solid-state NMR (ssNMR) spectroscopy is a technique for characterizing atomic level structure in solid materials e.g. powders, single crystals and amorphous samples and tissues using nuclear magnetic resonance (NMR) spectroscopy. The anisotropic part of many spin interactions are present in solid-state NMR, unlike in solution-state NMR where rapid tumbling motion averages out many of the spin interactions. As a result, solid-state NMR spectra are characterised by larger linewidths than in solution state NMR, which can be utilized to give quantitative information on the molecular structure, conformation and dynamics of the material. Solid-state NMR is often combined with magic angle spinning to remove anisotropic interactions and improve the resolution as well as the sensitivity of the technique.

Carbon-13 (C13) nuclear magnetic resonance is the application of nuclear magnetic resonance (NMR) spectroscopy to carbon. It is analogous to proton NMR and allows the identification of carbon atoms in an organic molecule just as proton NMR identifies hydrogen atoms. 13C NMR detects only the 13
C
 isotope. The main carbon isotope, 12
C
 is not detected. Although much less sensitive than 1H NMR spectroscopy, 13C NMR spectroscopy is widely used for characterizing organic and organometallic compounds.

Nuclear magnetic resonance spectroscopy of proteins is a field of structural biology in which NMR spectroscopy is used to obtain information about the structure and dynamics of proteins, and also nucleic acids, and their complexes. The field was pioneered by Richard R. Ernst and Kurt Wüthrich at the ETH, and by Ad Bax, Marius Clore, Angela Gronenborn at the NIH, and Gerhard Wagner at Harvard University, among others. Structure determination by NMR spectroscopy usually consists of several phases, each using a separate set of highly specialized techniques. The sample is prepared, measurements are made, interpretive approaches are applied, and a structure is calculated and validated.

The heteronuclear single quantum coherence or heteronuclear single quantum correlation experiment, normally abbreviated as HSQC, is used frequently in NMR spectroscopy of organic molecules and is of particular significance in the field of protein NMR. The experiment was first described by Geoffrey Bodenhausen and D. J. Ruben in 1980. The resulting spectrum is two-dimensional (2D) with one axis for proton (1H) and the other for a heteronucleus, which is usually 13C or 15N. The spectrum contains a peak for each unique proton attached to the heteronucleus being considered. The 2D HSQC can also be combined with other experiments in higher-dimensional NMR experiments, such as NOESY-HSQC or TOCSY-HSQC.

Two-dimensional nuclear magnetic resonance spectroscopy is a set of nuclear magnetic resonance spectroscopy (NMR) methods which give data plotted in a space defined by two frequency axes rather than one. Types of 2D NMR include correlation spectroscopy (COSY), J-spectroscopy, exchange spectroscopy (EXSY), and nuclear Overhauser effect spectroscopy (NOESY). Two-dimensional NMR spectra provide more information about a molecule than one-dimensional NMR spectra and are especially useful in determining the structure of a molecule, particularly for molecules that are too complicated to work with using one-dimensional NMR.

<span class="mw-page-title-main">Veratridine</span> Steroidal alkaloid found in plants of the lily family

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<span class="mw-page-title-main">Exclusive correlation spectroscopy</span>

Exclusive correlation spectroscopy (ECOSY) is an NMR correlation experiment introduced by O. W. Sørensen, Christian Griesinger, Richard R. Ernst and coworkers for the accurate measurement of small J-couplings.

Adriaan "Ad" Bax is a Dutch-American molecular biophysicist. He was born in the Netherlands and is the Chief of the Section on Biophysical NMR Spectroscopy at the National Institutes of Health. He is known for his work on the methodology of biomolecular NMR spectroscopy.

James Benjamin Martel is a physician, surgeon and scientist. He is former Chair of Surgery, Mercy San Juan Medical Center, former Chief of Ophthalmology, Otolaryngology (ENT), and Plastic Surgery, Sutter Roseville Medical Center. He is the former Director of Ophthalmology, Sutter General and Memorial Hospitals and Assistant Professor of Ophthalmology and Radiology, Johns Hopkins Medical School and Wilmer Ophthalmological Institute. He is currently Clinical Professor of Ophthalmology and Associate Dean of Graduate Medical Education in California Northstate University College of Medicine.

In physical organic chemistry, the Swain–Lupton equation is a linear free energy relationship (LFER) that is used in the study of reaction mechanisms and in the development of quantitative structure activity relationships for organic compounds. It was developed by C. Gardner Swain and Elmer C. Lupton Jr. in 1968 as a refinement of the Hammett equation to include both field effects and resonance effects.

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Real-time magnetic resonance imaging (RT-MRI) refers to the continuous monitoring ("filming") of moving objects in real time. Because MRI is based on time-consuming scanning of k-space, real-time MRI was possible only with low image quality or low temporal resolution. Using an iterative reconstruction algorithm these limitations have recently been removed: a new method for real-time MRI achieves a temporal resolution of 20 to 30 milliseconds for images with an in-plane resolution of 1.5 to 2.0 mm. Real-time MRI promises to add important information about diseases of the joints and the heart. In many cases MRI examinations may become easier and more comfortable for patients.

<span class="mw-page-title-main">Antony John Williams</span> British chemist

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Nucleic acid NMR is the use of nuclear magnetic resonance spectroscopy to obtain information about the structure and dynamics of nucleic acid molecules, such as DNA or RNA. It is useful for molecules of up to 100 nucleotides, and as of 2003, nearly half of all known RNA structures had been determined by NMR spectroscopy.

<span class="mw-page-title-main">Jürgen Hennig</span> German chemist and medical physicist

Jürgen Klaus Hennig is a German chemist and medical physicist. Internationally he is considered to be one of the pioneers of Magnetic Resonance Imaging for clinical diagnostics. He is the Scientific Director of the Department of Diagnostic Radiology and Chairman of the Magnetic Resonance Development and Application Center (MRDAC) at the University Medical Center Freiburg. In the year 2003 he was awarded the Max Planck Research Award in the category of Biosciences and Medicine.

PREDITOR is a freely available web-server for the prediction of protein torsion angles from chemical shifts. For many years it has been known that protein chemical shifts are sensitive to protein secondary structure, which in turn, is sensitive to backbone torsion angles. torsion angles are internal coordinates that can be used to describe the conformation of a polypeptide chain. They can also be used as constraints to help determine or refine protein structures via NMR spectroscopy. In proteins there are four major torsion angles of interest: phi, psi, omega and chi-1. Traditionally protein NMR spectroscopists have used vicinal J-coupling information and the Karplus relation to determine approximate backbone torsion angle constraints for phi and chi-1 angles. However, several studies in the early 1990s pointed out the strong relationship between 1H and 13C chemical shifts and torsion angles, especially with backbone phi and psi angles. Later a number of other papers pointed out additional chemical shift relationships with chi-1 and even omega angles. PREDITOR was designed to exploit these experimental observations and to help NMR spectroscopists easily predict protein torsion angles from chemical shift assignments. Specifically, PREDITOR accepts protein sequence and/or chemical shift data as input and generates torsion angle predictions for phi, psi, omega and chi-1 angles. The algorithm that PREDITOR uses combines sequence alignment, chemical shift alignment and a number of related chemical shift analysis techniques to predict torsion angles. PREDITOR is unusually fast and exhibits a very high level of accuracy. In a series of tests 88% of PREDITOR’s phi/psi predictions were within 30 degrees of the correct values, 84% of chi-1 predictions were correct and 99.97% of PREDITOR’s predicted omega angles were correct. PREDITOR also estimates the torsion angle errors so that its torsion angle constraints can be used with standard protein structure refinement software, such as CYANA, CNS, XPLOR and AMBER. PREDITOR also supports automated protein chemical shift re-referencing and the prediction of proline cis/trans states. PREDITOR is not the only torsion angle prediction software available. Several other computer programs including TALOS, TALOS+ and DANGLE have also been developed to predict backbone torsion angles from protein chemical shifts. These stand-alone programs exhibit similar prediction performance to PREDITOR but are substantially slower.

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David Lyndon Emsley FRSC is a British chemist specialising in solid-state nuclear magnetic resonance and a professor at EPFL. He was awarded the 2012 Grand Prix Charles-Leopold Mayer of the French Académie des Sciences and the 2015 Bourke Award of the Royal Society of Chemistry.

<span class="mw-page-title-main">Geoffrey Bodenhausen</span> French chemist

Geoffrey Bodenhausen is a French chemist specializing in nuclear magnetic resonance, being highly cited in his field. He is a Corresponding member of the Royal Netherlands Academy of Arts and Sciences and a Fellow of the American Physical Society. He is professeur émérite at the Department of Chemistry at the École Normale Supérieure (ENS) in Paris and professeur honoraire at the Laboratory of Biomolecular Magnetic Resonance of the École Polytechnique Fédérale de Lausanne (EPFL). He is a member of the editorial board of the journal Progress in Nuclear Magnetic Resonance Spectroscopy. He is the chair of the editorial board of the journal Magnetic Resonance.

References

  1. ↑ Awards, Publications and Recognition for Gary Martin Photography
  2. ↑ Gary Martin Photography biography
  3. ↑ Interview with Gary Martin at Reactive Reports, by David Bradley; posted February 7, 2006; retrieved April 18, 2011
  4. ↑ Martin, G.E.; Crouch, R.C.; Zens, A.P. (1998). "Gradient submicro inverse detection: rapid acquisition of inverse-detected heteronuclear chemical shift correlation data on submicromole quantities of material". Magnetic Resonance in Chemistry. 36 (7): 551–557. doi:10.1002/(SICI)1097-458X(199807)36:7<551::AID-OMR332>3.0.CO;2-F. S2CID   98408800.
  5. ↑ Martin, G.E.; Hadden, C.E.; Russell, D.J.; Kaluzny, B.D.; Guido, J.E.; Duholke, W.K.; Stiemsma, B.A.; Thamann, T.J.; Crouch, R.C.; Blinov, K.A.; Elyashberg, M.E.; Martirosian, E.R.; Molodtsov, S.G.; Williams, A.J.; Schiff Jr, P.L. (2002). "Identification of Degradants of a Complex Alkaloid Using NMR Cryoprobe Technology and ACD/Structure Elucidator". J. Heterocyclic Chem. 39 (6): 1241–1250. doi:10.1002/jhet.5570390619.
  6. ↑ Blinov, K.; Elyashberg, M.; Martirosian, E. R.; Molodtsov, S. G.; Williams, A. J.; Sharaf, M. H. M.; Schiff, P. L.; Crouch, R. C.; Martin, G. E.; Hadden, C. E.; Guido, J. E. (2003). "Quindolinocryptotackieine: The Elucidation of a Novel Indoloquinoline Alkaloid Structure through the Use of Computer-Assisted Structure Elucidation and 2D-NMR". Magn. Reson. Chem. 41 (8): 577–584. doi: 10.1002/mrc.1227 .
  7. ↑ Elyashberg, M. E.; Blinov, K. A.; Martirosian, E. R.; Molodtsov, S. G.; Williams, A. J.; Martin, G. E. (2003). "Automated Structure Elucidation – The Benefits of a Symbiotic Relationship between the Spectroscopist and the Expert System". J. Heterocyclic Chem. 40 (6): 1017–1029. doi:10.1002/jhet.5570400610.
  8. ↑ Hadden, C.E.; Martin, G.E.; Krishnamurthy, V.V. (1999). "Improved Performance Accordion Heteronuclear Multiple-Bond Correlation Spectroscopy—IMPEACH-MBC". Journal of Magnetic Resonance. 140 (1): 274–280. Bibcode:1999JMagR.140..274H. doi:10.1006/jmre.1999.1840. PMID   10479572.
  9. ↑ Martin, G.E.; Hadden, C.E. (2000). "Long-range 1H-15N heteronuclear shift correlation at natural abundance (review)". J. Nat. Prod. 63 (4): 543–85. doi:10.1021/np9903191. PMID   10785437.
  10. ↑ Blinov, K.A.; Williams, A.J.; Hilton, B.D.; Irish, P.A.; Martin, G.E. (2007). "The Use of Unsymmetrical Indirect Covariance NMR Methods to Obtain the Equivalent of HSQC-NOESY Data". Magn. Reson. Chem. 45 (7): 544–546. doi:10.1002/mrc.1998. PMID   17437315. S2CID   46106410.
  11. ↑ Martin, G. E.; Irish, P. A.; Hilton, B. D.; Blinov, K. A.; Williams, A. J. (2007). "Utilizing Unsymmetrical Indirect Covariance Processing to Define 15N-13C Connectivity Networks". Magn. Reson. Chem. 45 (8): 624–627. doi:10.1002/mrc.2029. PMID   17563910. S2CID   34281811.
  12. ↑ Martin, G.E.; Hilton, B.D.; Irish, P.A.; Blinov, K.A.; Williams, A.J. (2007). "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 (10): 883–888. doi:10.1002/mrc.2064. PMID   17729230. S2CID   41359162.
  13. ↑ "Hall of Distinguished Alumni | UK College of Pharmacy".
  14. ↑ "Shoolery Award Recipient - SMASH - Small Molecule NMR Conference".
  15. ↑ "2016 EAS Award for Outstanding Achievements in NMR". February 2016.
  16. ↑ Martin, G.E.; Hadden, C.E. (1999). "Comparison of 1.7 mm Submicro and 3 mm Micro Gradient NMR Probes for the Acquisition of 1H-13C and 1H-15N Heteronuclear Shift Correlation Data". Magn. Reson. Chem. 37 (10): 721–729. doi:10.1002/(SICI)1097-458X(199910)37:10<721::AID-MRC525>3.0.CO;2-Z. S2CID   98184044.
  17. ↑ Russell, D.J.; Hadden, C.E.; Martin, G.E.; Gibson, A.A.; Zens, A.P.; Carolan, J.L. (2000). "A Comparison of Inverse-Detected Heteronuclear NMR Performance: Conventional 3 mm vs. 3 mm Cryogenic Probe Performance". J. Nat. Prod. 63 (8): 1047–1049. doi:10.1021/np0003140. PMID   10978194.
  18. ↑ G. E. Martin, M. Solntseva, and A. J. Williams "Applications of 15N NMR in Alkaloid Chemistry" Modern Alkaloids, E. Fattorusso and O. Taglialatela-Scafati, Wiley-VCH, New York, 2007, pp. 411-476 doi : 10.1002/9783527621071.ch14
  19. ↑ Crouch, R.C.; Davis, A.O.; Spitzer, T.D.; Martin, G.E.; Sharaf, M.H.M.; Schiff, P.L.; Phoebe, C.H.; Tackie, A.N. (1995). "Elucidation of the Structure of Quindolinone, a Minor Alkaloid of Cryptolepis sanguinolenta: Submilligram 1H-13C and 1H-15N Heteronuclear Shift Correlation Experiments Using Micro Inverse-Detection". J. Heterocyclic Chem. 32 (3): 1077–1080. doi:10.1002/jhet.5570320369.
  20. ↑ Liu, Y.; Sauri, J.; Mavers, E.; Peczuh, M.W.; Hiemstra, H.; Clardy, J.; Martin, G.E.; Williamson, R.T. (2017). "Unequivocal determination of complex molecular structures using anisotropic NMR measurements". Science. 356 (6333): eaam5349. doi: 10.1126/science.aam5349 . PMC   6596297 . PMID   28385960.
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