Publications by authors named "Bikash Baishya"

32 Publications

NMR based CSF metabolomics in tuberculous meningitis: correlation with clinical and MRI findings.

Metab Brain Dis 2022 Jan 14. Epub 2022 Jan 14.

Department of Neurology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, 226014, India.

We report the potential role of H Nuclear Magnetic Resonance (NMR) based metabolomics in tuberculous meningitis (TBM). We also correlate the significant metabolites with clinical-radiological parameters. Forty-three patients with TBM were included, and their severity of meningitis was graded as stages I to III, and patients with positive Mycobacterium tuberculosis or its nucleic acid was considered as definite TBM. H NMR-based metabolomic study was performed on (CSF) samples, and the significant metabolites compared to healthy controls were identified. Outcome at three months was defined as death, poor and good based on the modified Rankin Scale. These metabolites were compared between definite and probable groups of TBM, and also correlated with MRI findings. About 11 metabolites were found to be significant for distinguishing TBM from the controls. In TBM, lactate, glutamate, alanine, arginine, 2-hydroxyisobutyrate, formate, and cis-aconitate were upregulated, and glucose, fructose, glutamine, and myo-inositol were downregulated compared to the controls. For differentiating TBM from the controls, the AUC of the ROC curve generated using these significant metabolites was 0.99, with a 95% confidence interval from 0.96 to 1, demonstrating that these metabolites were able to classify cases with good sensitivity and specificity. Lactate concentration in CSF correlated with hemoglobin, CSF glucose, and infarction. The outcome did not correlate with metabolomics parameters. NMR-based CSF metabolomics have a potential role in differentiating TBM from the controls.
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http://dx.doi.org/10.1007/s11011-021-00860-yDOI Listing
January 2022

Accelerated C detection by concentrating the NMR sample in a biphasic solvent system.

Analyst 2021 Oct 25;146(21):6582-6591. Epub 2021 Oct 25.

Centre of Biomedical Research (Formerly Centre of Biomedical Magnetic Resonance), SGPGIMS Campus, Raebareli Road, Lucknow, 226014, India.

CDCl is the most frequently used solvent for the NMR investigation of organic compounds. Busy chemistry labs need to investigate hundreds of compounds daily. While H NMR investigation takes a couple of minutes, recording C NMR spectra necessitates hours of signal averaging due to the low abundance and low sensitivity of C nuclei. The longer acquisition time for C NMR results in a loss of precious spectrometer time in a shared multi-user environment. A regular 5 mm o.d. NMR tube is the most commonly used tube for NMR in organic chemistry labs and is also the cheapest option. We show that for analytes soluble in the CDCl solvent using a regular 5 mm o.d. NMR tube, the speed of C observation can be enhanced by a factor of two by resorting to a sample preparation method that employs a biphasic system made of HO or DO at the top of another layer of CDCl. By using the biphasic system of two immiscible solvents, the analyte can be concentrated in the CDCl layer (within the more sensitive volume of the NMR coil), resulting in the improvement of the signal to noise ratio (SNR) by a factor of up to 1.8 for C and 2D H-C HSQC spectra, which results in more than two-fold reduction in the experimental time. H NMR and other 2D NMR also get a sensitivity boost. The amount of CDCl required for sample preparation can also be reduced by 40% using this biphasic system (CDCl/HO). Sample preparation in such an immiscible biphasic system is effortless and straightforward. The performance of such biphasic samples is closer to that of Shigemi tubes and better than that of 3 mm o.d. tubes.
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http://dx.doi.org/10.1039/d1an00470kDOI Listing
October 2021

H NMR-Based Metabolic Signatures in the Liver and Brain in a Rat Model of Hepatic Encephalopathy.

J Proteome Res 2020 09 24;19(9):3668-3679. Epub 2020 Aug 24.

Department of Biochemistry, Basic Medical Science Block-II, Panjab University, Sector-25, Chandigarh 160014, India.

Hepatic encephalopathy (HE) is a debilitating neuropsychiatric complication associated with acute and chronic liver failure. It is characterized by diverse symptoms with variable severity that includes cognitive and motor deficits. The aim of the study is to assess metabolic alterations in the brain and liver using nuclear magnetic resonance (NMR) spectroscopy and subsequent multivariate analyses to characterize metabolic signatures associated with HE. HE was developed by bile duct ligation (BDL) that resulted in hepatic dysfunctions and cirrhosis as shown by liver function tests. Metabolic profiles from control and BDL rats indicated increased levels of lactate, branched-chain amino acids (BCAAs), glutamate, and choline in the liver, whereas levels of glucose, phenylalanine, and pyridoxine were decreased. In brain, the levels of lactate, acetate, succinate, citrate, and malate were increased, while glucose, creatine, isoleucine, leucine, and proline levels were decreased. Furthermore, neurotransmitters such as glutamate and GABA were increased, whereas choline and myo-inositol were decreased. The alterations in neurotransmitter levels resulted in cognitive and motor defects in BDL rats. A significant correlation was found among alterations in NAA/choline, choline/creatine, and NAA/creatine with behavioral deficits. Thus, the data suggests impairment in metabolic pathways such as the tricarboxylic acid (TCA) cycle, glycolysis, and ketogenesis in the liver and brain of animals with HE. The study highlights that metabolic signatures could be potential markers to monitor HE progression and to assess therapeutic interventions.
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http://dx.doi.org/10.1021/acs.jproteome.0c00165DOI Listing
September 2020

Pure shift HMQC: Resolution and sensitivity enhancement by bilinear rotation decoupling in the indirect and direct dimensions.

J Magn Reson 2020 02 3;311:106684. Epub 2020 Jan 3.

Centre of Biomedical Research (Formerly Centre of Biomedical Magnetic Resonance), SGPGIMS Campus, Raebareli Road, Lucknow 226014, India. Electronic address:

The heteronuclear multiple-quantum coherence in the indirect dimension of the two-dimensional HMQC experiment evolves under the passive H-H J-couplings leading to multiplet structures in the F dimension. Besides, H-H J-multiplets appear in the direct dimension as well. Thus, multiplets along both dimensions lower the resolution and sensitivity of this technique, when high resolution is required along both dimensions. An efficient broadband homodecoupling scheme along the F dimension of the HMQC experiment has not been realized to date. We have implemented broadband homonuclear decoupling using bilinear rotation decoupling (BIRD) by adding a H SQ evolution period followed by BIRD before the H-C multiple-quantum evolution period in the HMQC. In the direct time domain, BIRD is implemented using a real-time or single-scan scheme, which further improves resolution and sensitivity of this technique. The resulting pure shift HMQC provides singlet peak per chemical site along F as well as F axes and, hence, better resolution and sensitivity than conventional HMQC spectrum for all peaks except diastereotopic methylene protons. Due to the incorporation of the BIRD, the indirect time domain becomes double in length compared to the conventional HMQC. However, slow relaxation of small molecules favors better sensitivity for ps-HMQC relative to conventional HMQC under all conditions. We also found that the sensitivity of ps-HMQC is only slightly less than ps-HSQC for small molecules.
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http://dx.doi.org/10.1016/j.jmr.2020.106684DOI Listing
February 2020

DQF J-RES NMR: Suppressing the singlet signals for improving the J-RES spectra from complex mixtures.

J Magn Reson 2019 04 23;301:19-29. Epub 2019 Feb 23.

Center of Biomedical Research (Formerly Centre of Biomedical Magnetic Resonance), SGPGIMS Campus, Raebareli Road, Lucknow 226014, India. Electronic address:

Two-dimensional J-RESolved spectroscopy (J-RES) finds routine use in metabolomics for reducing signal overlap as it separates chemical shift and multiplet information along two frequency axes. However, only magnitude mode of the experiment is practical which prevents exploitation of its full resolving power. Tailing from high-intensity metabolite peaks often obscure nearby low-intensity metabolite peaks which leads to ambiguity in assignment of metabolites. Absorptive mode J-RES spectroscopy offers better-resolving power but comes at the cost of either sensitivity or complicated post-processing. Quite often for certain complex mixtures such as bio-fluids some components of the mixture display intense singlet signals which dominate the whole spectrum resulting in less reliable detection of weaker metabolite signals. Multi-frequency presaturation could suppress these intense singlets but will also remove the useful weaker multiplet peaks which are either totally eclipsed with the intense singlets or very close in frequency. We show that by using a double quantum filter (DQF) in magnitude mode J-RES technique, the intensity of the strong singlet metabolite peaks can be reduced relative to the intensity of the sparsely present multiplet metabolite signals. This approach leads to the identification of many weak intensity multiplet peaks which are otherwise undetected due to their overlap with intense singlet peaks in regular J-RES as well as 1D H spectra. Although the improved intensity of most of the weaker peaks relative to the strong singlet peaks is observed, some multiplets can disappear due to the delay-dependent modulation of the signals by the DQF. A few DQF J-RES spectra recorded with different DQF delays, therefore, produce better assignment when analyzed together. The technique is demonstrated on a mixture of eight compounds, human urine, and plant extract samples.
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http://dx.doi.org/10.1016/j.jmr.2019.02.003DOI Listing
April 2019

Identification of metabolites in coriander seeds (Coriandrum Sativum L.) aided by ultrahigh resolution total correlation NMR spectroscopy.

Magn Reson Chem 2019 06 18;57(6):304-316. Epub 2019 Mar 18.

Centre of Biomedical Research, SGPGIMS Campus, Lucknow, UP, India.

NMR is a fast method for obtaining a holistic snapshot of the metabolome and also offers quantitative information without separating the compounds present in a complex mixture. Identification of the metabolites present in a plant extract sample is a crucial step for all plant metabolomics studies. In the present work, we used various two dimensional (2D) NMR methods such as J-resolved NMR, total correlation spectroscopy (TOCSY), and heteronuclear single quantum coherence sensitivity enhanced NMR spectroscopy for the identification of 36 common metabolites present in Coriandrum sativum L. seed extract. The identified metabolites belong to the following classes: organic acids, amino acids, and carbohydrates. H NMR spectra of such complex mixtures in general display tremendous signal overlap due to the presence of a large number of metabolites with closely resonating multiplet signals. This signal overlapping leads to ambiguity in an assignment, and hence, identification of metabolites becomes tedious or impossible in many cases. Therefore, the utility of pure-shift proton spectrum along the indirect (F ) dimension of the F -PSYCHE-TOCSY spectrum is demonstrated for overcoming ambiguity in assignment of metabolites in crowded spectral regions from Coriandrum sativum L. seed extract sample. Because pure-shift NMR methods yield ultrahigh resolution spectrum (i.e., a singlet peak per chemical site) along one or more dimensions, such spectra provide better identification of metabolites compared with regular 2D TOCSY where signal overlap and peak distortions lead to ambiguity in the assignment. Nine metabolites were unambiguously assigned by pure-shift F -PSYCHE-TOCSY spectrum, which was unresolved in regular TOCSY spectrum.
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http://dx.doi.org/10.1002/mrc.4850DOI Listing
June 2019

Insight into old and new pure shift nuclear magnetic resonance methods for enantiodiscrimination.

Magn Reson Chem 2018 10 16;56(10):876-892. Epub 2018 May 16.

School of Chemistry, University of Nottingham, University Park, Nottingham, NG7 2RD, UK.

Enantiodiscrimination and their quantification using nuclear magnetic resonance (NMR) spectroscopy has always been a subject of great interest. Proton is the nucleus of choice for enantiodiscrimination due to its high sensitivity and ubiquitous presence in nature. Despite its advantages, enantiodiscrimination suffers from extensive signal splitting by the proton-proton scalar couplings, which give complex multiplets that spread over a frequency range of some tens of hertz. These multiplets often overlap, further complicating interpretation of the spectra and quantifications. In the present review, we discuss some of the recent developments in the pure shift H NMR based methods for enantiomer resolution and enantiodiscrimination. We also compare various pure shift methods used for enantiodiscrimination and measurement of enantiomeric excess, considering the fact that conventional H NMR fails to provide any detailed insight.
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http://dx.doi.org/10.1002/mrc.4719DOI Listing
October 2018

Curcumin stably interacts with DNA hairpin through minor groove binding and demonstrates enhanced cytotoxicity in combination with FdU nucleotides.

Biochim Biophys Acta Gen Subj 2018 Mar 28;1862(3):485-494. Epub 2017 Oct 28.

Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.

We report, based on biophysical studies and molecular mechanical calculations that curcumin binds DNA hairpin in the minor groove adjacent to the loop region forming a stable complex. UV-Vis and fluorescence spectroscopy indicated interaction of curcumin with DNA hairpin. In this novel binding motif, two ɣ H of curcumin heptadiene chain are closely positioned to the A-H8 and A-H8, while G-H8 is located in the close proximity of curcumin α H. Molecular dynamics (MD) simulations suggest, the complex is stabilized by noncovalent forces including; π-π stacking, H-bonding and hydrophobic interactions. Nuclear magnetic resonance (NMR) spectroscopy in combination with molecular dynamics simulations indicated curcumin is bound in the minor groove, while circular dichroism (CD) spectra suggested minute enhancement in base stacking and a little change in DNA helicity, without significant conformational change of DNA hairpin structure. The DNA:curcumin complex formed with FdU nucleotides rather than Thymidine, demonstrated enhanced cytotoxicity towards oral cancer cells relative to the only FdU substituted hairpin. Fluorescence co-localization demonstrated stability of the complex in biologically relevant conditions, including its cellular uptake. Acridine orange/EtBr staining further confirmed the enhanced cytotoxic effects of the complex, suggesting apoptosis as mode of cell death. Thus, curcumin can be noncovalently complexed to small DNA hairpin for cellular delivery and the complex showed increased cytotoxicity in combination with FdU nucleotides, demonstrating its potential for advanced cancer therapy.
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http://dx.doi.org/10.1016/j.bbagen.2017.10.018DOI Listing
March 2018

Parallel acquisition of slice-selective H-H soft COSY spectra.

J Magn Reson 2017 11 20;284:80-85. Epub 2017 Sep 20.

Centre of Biomedical Research (Formerly Centre of Biomedical Magnetic Resonance), SGPGIMS Campus, Raebareli Road, Lucknow 226014, India. Electronic address:

A method is demonstrated for parallel acquisition of several slice selective soft COSY proton spectra. Application of a slice selective mixing pulse in a selective correlation experiment allows slice selective coherence transfer between different coupled spin pairs. During such slice selective coherence transfer, the spin states of the passive spins are undisturbed. In other words, slice selective coherence transfer executes spin-state selective coherence transfer between a given spin and all its coupled neighbours. This results in a final spectrum which contains multiple soft cosy spectra between a given signal(s) and all its coupled signals, significantly reducing experimental time. This provides access to all the couplings for a given proton site and its coupled partners.
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http://dx.doi.org/10.1016/j.jmr.2017.09.012DOI Listing
November 2017

Analyses of Complex Mixtures by F Homo-Decoupled Diagonal Suppressed Total Correlation Spectroscopy.

Chemphyschem 2017 Nov 9;18(21):3076-3082. Epub 2017 Oct 9.

Centre of Biomedical Research (Formerly Centre of Biomedical Magnetic Resonance), SGPGIMS Campus, Raebareli Road, Lucknow, 226014, U. P., India.

A diagonal suppressed F decoupled total correlation spectroscopy(TOCSY) experiment is developed for analyses of complex mixtures. In 2D homonuclear correlation, assignment of the cross peaks is crucial for structure elucidation. However, when cross peaks are close to the diagonal peaks in overcrowded spectral regions, their assignment becomes tedious. In complex mixtures, the presence of multiple spectra along with broad and complex proton multiplets owing to homonuclear scalar couplings degrade the resolution to the extent that assignment of various cross peaks becomes tedious or impossible. Herein, a diagonal suppressed total correlation technique with F decoupling is presented to improve the resolution of the cross peaks. The resolution of the cross peaks is improved by both diagonal suppression as well as the collapse of the multiplets to singlets. Application of the method to a few mixtures of organic compounds reveals better identification of the cross peaks relative to other TOCSY variants.
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http://dx.doi.org/10.1002/cphc.201700662DOI Listing
November 2017

Altered metabolites of the rat hippocampus after mild and moderate traumatic brain injury - a combined in vivo and in vitro H-MRS study.

NMR Biomed 2017 Oct 31;30(10). Epub 2017 Jul 31.

NMR Research Centre, Institute of Nuclear Medicine and Allied Sciences, Delhi, India.

Traumatic brain injury (TBI) has been shown to affect hippocampus-associated learning, memory and higher cognitive functions, which may be a consequence of metabolic alterations. Hippocampus-associated disorders may vary depending on the severity of injury [mild TBI (miTBI) and moderate TBI (moTBI)] and time since injury. The underlying hippocampal metabolic irregularities may provide an insight into the pathological process following TBI. In this study, in vivo and in vitro proton magnetic resonance spectroscopy ( H-MRS) data were acquired from the hippocampus region of controls and TBI groups (miTBI and moTBI) at D0 (pre-injury), 4 h, Day 1 and Day 5 post-injury (PI). In vitro MRS results indicated trauma-induced changes in both miTBI and moTBI; however, in vivo MRS showed metabolic alterations in moTBI only. miTBI and moTBI showed elevated levels of osmolytes indicating injury-induced edema. Altered levels of citric acid cycle intermediates, glutamine/glutamate and amino acid metabolism indicated injury-induced aberrant bioenergetics, excitotoxicity and oxidative stress. An overall similar pattern of pathological process was observed in both miTBI and moTBI, with the distinction of depleted N-acetylaspartate levels (indicating neuronal loss) at 4 h and Day 1 and enhanced lactate production (indicating heightened energy depletion leading to the commencement of the anaerobic pathway) at Day 5 in moTBI. To the best of our knowledge, this is the first study to investigate the hippocampus metabolic profile in miTBI and moTBI simultaneously using in vivo and in vitro MRS.
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http://dx.doi.org/10.1002/nbm.3764DOI Listing
October 2017

Real time band selective F -decoupled proton NMR for the demixing of overlay spectra of chiral molecules.

Magn Reson Chem 2017 Jun 2;55(6):553-558. Epub 2016 Dec 2.

Centre of Biomedical Research, SGPGIMS Campus, Lucknow, U. P., India.

The small chemical shift dispersion and complex multiplicity pattern in proton NMR limit quantifications, for instance the determination of enantiomeric excess (ee) for an enantiomeric mixture. Herein, we present a simple proton-proton correlation experiment with band selective homonuclear (BASH) decoupling in both F and F dimensions, for the removal of scalar and residual dipolar couplings to provide collapsed singlet for each chemical site. The method has been demonstrated to separate the severely overlapped spectra of enantiomers using both chiral isotropic and anisotropic phases as well as a small biomolecule, particularly for the diastereotopic protons and also for the determination of ee. Copyright © 2016 John Wiley & Sons, Ltd.
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http://dx.doi.org/10.1002/mrc.4547DOI Listing
June 2017

Real-time bilinear rotation decoupling in absorptive mode J-spectroscopy: Detecting low-intensity metabolite peak close to high-intensity metabolite peak with convenience.

J Magn Reson 2016 05 10;266:51-8. Epub 2016 Mar 10.

Centre of Biomedical Research (Formerly Centre of Biomedical Magnetic Resonance), SGPGIMS Campus, Raebareli Road, Lucknow 226014, India. Electronic address:

"Pure shift" NMR spectra display singlet peak per chemical site. Thus, high resolution is offered at the cost of valuable J-coupling information. In the present work, real-time BIRD (BIlinear Rotation Decoupling) is applied to the absorptive-mode 2D J-spectroscopy to provide pure shift spectrum in the direct dimension and J-coupling information in the indirect dimension. Quite often in metabolomics, proton NMR spectra from complex bio-fluids display tremendous signal overlap. Although conventional J-spectroscopy in principle overcomes this problem by separating the multiplet information from chemical shift information, however, only magnitude mode of the experiment is practical, sacrificing much of the potential high resolution that could be achieved. Few J-spectroscopy methods have been reported so far that produce high-resolution pure shift spectrum along with J-coupling information for crowded spectral regions. In the present work, high-quality J-resolved spectrum from important metabolomic mixture such as tissue extract from rat cortex is demonstrated. Many low-intensity metabolite peaks which are obscured by the broad dispersive tails from high-intensity metabolite peaks in regular magnitude mode J-spectrum can be clearly identified in real-time BIRD J-resolved spectrum. The general practice of removing such spectral overlap is tedious and time-consuming as it involves repeated sample preparation to change the pH of the tissue extract sample and subsequent spectra recording.
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http://dx.doi.org/10.1016/j.jmr.2016.03.002DOI Listing
May 2016

Real-time band-selective homonuclear proton decoupling for improving sensitivity and resolution in phase-sensitive J-resolved spectroscopy.

Chemphyschem 2015 Aug 14;16(12):2687-91. Epub 2015 Jul 14.

Centre of Biomedical Research (Formerly Centre of Biomedical Magnetic Resonance), SGPGIMS Campus, Raebareli Road, Lucknow-226014, U. P. (India), Fax: (+91) 522-2668215.

Real-time band-selective homonuclear (1) H decoupling during data acquisition of z-filtered J-resolved spectroscopy produces (1) H-decoupled (1) H NMR spectra and leads to sensitivity enhancement and improved resolution, and thus aids the measurement of J couplings and residual dipolar couplings in crowded regions of (1) H NMR spectrum. High quality spectra from peptides, organic molecules, and also from enantiomers dissolved in weakly aligned chiral media are reported.
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http://dx.doi.org/10.1002/cphc.201500377DOI Listing
August 2015

Diagonal free homonuclear correlation using heteronuclei at natural abundance.

Authors:
Bikash Baishya

J Magn Reson 2015 Jul 7;256:52-59. Epub 2015 May 7.

Center of Biomedical Research (Formerly Centre of Biomedical Magnetic Resonance), SGPGIMS Campus, Raebareli Road, Lucknow 226014, India. Electronic address:

Homonuclear correlated spectroscopy such as COSY and TOCSY provides crucial structural information. In all homonuclear correlation, the most intense peaks are represented by the diagonal. As a result, the useful cross peaks close to the diagonal get obscured by the huge tails of diagonal peaks. Herein, we show that by editing the proton magnetization by a 13C nucleus in natural abundance, it is possible to eliminate the inphase coherence or untransferred magnetization that leads to the diagonal peak while retaining the antiphase coherence or transferred magnetization required for creation of cross peak. After the coherence transfer step, the untransferred magnetization directly attached to 13C evolves under one bond heteronuclear coupling while the transferred transverse magnetization directly attached to remote 12C does not. As a result, the untransferred magnetization directly attached to 13C can be converted to an unobservable heteronuclear multiple quantum coherence leading to a diagonal free correlated spectrum with a sensitivity penalty of two orders of magnitude but comparable to HSQC kind of experiments at natural abundance. The method demonstrated for COSY and TOCSY allows all proton-proton correlations to be observed except the geminal proton-proton correlations. Further, protons directly attached to heteronuclei other than 13C must be scalar coupled to protons directly attached to 13C to have a detectable cross peak.
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http://dx.doi.org/10.1016/j.jmr.2015.04.008DOI Listing
July 2015

Elimination of Zero-Quantum artifacts and sensitivity enhancement in perfect echo based 2D NOESY.

J Magn Reson 2015 Mar 7;252:41-8. Epub 2015 Jan 7.

Center of Biomedical Research (Formerly Centre of Biomedical Magnetic Resonance), SGPGIMS Campus, Raebareli Road, Lucknow 226014, India.

Zero-Quantum artifacts seriously degrade the performance of 2D NOESY. Homonuclear J-evolution during t(1) period generates Zero-Quantum and other higher quantum coherences which represent the magnetization loss and the artifacts created. We demonstrate that creation of such artifacts itself can be prevented for shorter t1 period by a perfect echo based decoupling technique during t1 period in a single scan. This is in contrast to existing methods that create unwanted coherence, and subsequently suppress that to produce a clean spectrum with a sensitivity penalty. Although decoupling performance of the present scheme remains robust for echo time 2τ short compared to 1/2J, we show that even a partial decoupling effect for extended t(1) (=2τ) period up to 100 ms along with a Zero-Quantum filter generates NOE spectrum from Cyclosporine A, in which majority of the cross peaks displayed partial sensitivity enhancement with few exceptions. However, in crowded proton spin systems like menthol, the enhancements were not observed and perfect echo NOESY displays similar performance as Zero-Quantum filtered NOESY.
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http://dx.doi.org/10.1016/j.jmr.2014.12.007DOI Listing
March 2015

"Perfect echo" INEPT: more efficient heteronuclear polarization transfer by refocusing homonuclear J-coupling interaction.

J Magn Reson 2014 May 3;242:143-54. Epub 2014 Mar 3.

Center of Biomedical Research (Formerly Centre of Biomedical Magnetic Resonance), SGPGIMS Campus, Raebareli Road, Lucknow 226014, India.

A "perfect echo" based INEPT experiment that demonstrates more efficient heteronuclear polarization transfer over conventional INEPT has been developed. This scheme refocuses the effect of homonuclear (1)H-(1)H J-evolution and simultaneously allows heteronuclear (13)C-(1)H J-evolution to continue during INEPT. This improves one bond heteronuclear polarization transfer efficiency at longer INEPT transfer delays and also enhances the sensitivity of long range INEPT. The refocusing of homonuclear (1)H-(1)H J-coupling could be achieved by doubling the INEPT transfer period leading to a doubling of T2 losses. Therefore, the sensitivity gain is observed when loss of magnetization due to homonuclear (1)H-(1)H J-modulation is more severe than that of T2 decay. However, in general, INEPT transfer period is rather short compared to the longer T2 observed in small molecules. The long range PE-INEPT transfer to carbonyl carbon in beta-butyrolactone, showed much faster build up of C-13 signal than conventional long range INEPT as the long range heteronuclear J-coupling is comparable in magnitude to homonuclear (1)H-(1)H J-coupling in this case. For one bond heteronuclear polarization transfer at shorter delay, PE-INEPT and conventional INEPT displays equal transfer efficiency. Efficient polarization transfer is observed for small molecules dissolved in isotropic as well as weakly aligned media. Further, simulation results obtained using the full propagator and product operator analysis agree well with the experimental observations.
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http://dx.doi.org/10.1016/j.jmr.2014.02.017DOI Listing
May 2014

Super-resolved parallel MRI by spatiotemporal encoding.

Magn Reson Imaging 2014 Jan 11;32(1):60-70. Epub 2013 Oct 11.

Chemical Physics Department, Weizmann Institute of Science, 76100 Rehovot, Israel.

Recent studies described an "ultrafast" scanning method based on spatiotemporal (SPEN) principles. SPEN demonstrates numerous potential advantages over EPI-based alternatives, at no additional expense in experimental complexity. An important aspect that SPEN still needs to achieve for providing a competitive ultrafast MRI acquisition alternative, entails exploiting parallel imaging algorithms without compromising its proven capabilities. The present work introduces a combination of multi-band frequency-swept pulses simultaneously encoding multiple, partial fields-of-view, together with a new algorithm merging a Super-Resolved SPEN image reconstruction and SENSE multiple-receiving methods. This approach enables one to reduce both the excitation and acquisition times of sub-second SPEN acquisitions by the customary acceleration factor R, without compromises in either the method's spatial resolution, SAR deposition, or capability to operate in multi-slice mode. The performance of these new single-shot imaging sequences and their ancillary algorithms were explored and corroborated on phantoms and human volunteers at 3 T. The gains of the parallelized approach were particularly evident when dealing with heterogeneous systems subject to major T2/T2* effects, as is the case upon single-scan imaging near tissue/air interfaces.
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http://dx.doi.org/10.1016/j.mri.2013.07.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5081100PMC
January 2014

"Perfect echo" HMQC: sensitivity and resolution enhancement by broadband homonuclear decoupling.

J Magn Reson 2013 Sep 19;234:67-74. Epub 2013 Jun 19.

Center of Biomedical Magnetic Resonance, SGPGIMS Campus, Raebareli Road, Lucknow 226 014, India.

Homonuclear (1)H-(1)H J-modulation leads to J-multiplets in F1 dimension of 2D (1)H-(13)C HMQC spectra. This hampers unambiguous signal assignment for overcrowded (13)C spectra. Broadband homonuclear decoupling has been achieved in the indirect t1 evolution period by incorporating blocks of perfect echo. This method of perfect echo HMQC demonstrates better resolution and sensitivity than conventional HMQC spectra. The results on Cyclosporine demonstrate that the method is very efficient for refocusing geminal couplings in weakly coupled -(13)CH2 groups. Partial refocusing of vicinal couplings is also observed for -(13)CH and -(13)CH3 groups. Interpretation of the result based on product operator formalism is also given. Comparison of pe-HMQC, HMQC and HSQC reveals that the F1 linewidth of pe-HMQC is much narrower than HMQC and very close to that of HSQC for CH2 groups.
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http://dx.doi.org/10.1016/j.jmr.2013.06.004DOI Listing
September 2013

Quenching homonuclear couplings in magnetic resonance by trains of non-refocusing pulses.

J Magn Reson 2011 Aug 23;211(2):240-2. Epub 2011 May 23.

Institut des Sciences et Ingénierie Chimiques, Ecole Polytechnique Fédérale de Lausanne, EPFL, Batochime, 1015 Lausanne, Switzerland.

Trains of 2π or 4π pulses fail to refocus offsets but can suppress the effects of bilinear interactions such as homonuclear scalar couplings.
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http://dx.doi.org/10.1016/j.jmr.2011.05.009DOI Listing
August 2011

Transverse relaxation of scalar-coupled protons.

Chemphyschem 2010 Oct;11(15):3343-54

Laboratoire de Résonance Magnétique Biomoléculaire, Institut des Sciences et Ingénierie Chimiques, Ecole Polytechnique Fédérale de Lausanne, BCH, 1015 Lausanne, Switzerland.

In a preliminary communication (B. Baishya, T. F. Segawa, G. Bodenhausen, J. Am. Chem. Soc. 2009, 131, 17538-17539), we recently demonstrated that it is possible to obtain clean echo decays of protons in biomolecules despite the presence of homonuclear scalar couplings. These unmodulated decays allow one to determine apparent transverse relaxation rates R(2) (app) of individual protons. Herein, we report the observation of R(2) (app) for three methyl protons, four amide H(N) protons, and all 11 backbone H(α) protons in cyclosporin A. If the proton resonances overlap, their R(2) (app) rates can be measured by transferring their magnetization to neighboring (13)C nuclei, which are less prone to overlap. The R(2) (app) rates of protons attached to (13)C are faster than those attached to (12)C because of (13)C-(1)H dipolar interactions. The differences of these rates allow the determination of local correlation functions. Backbone H(N) and H(α) protons that have fast decay rates R(2) (app) also feature fast longitudinal relaxation rates R(1) and intense NOESY cross peaks that are typical of crowded environments. Variations of R(2) (app) rates of backbone H(α) protons in similar amino acids reflect differences in local environments.
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http://dx.doi.org/10.1002/cphc.201000350DOI Listing
October 2010

Apparent transverse relaxation rates in systems with scalar-coupled protons.

J Am Chem Soc 2009 Dec;131(48):17538-9

Institut des Sciences et Ingénierie Chimiques, Ecole Polytechnique Fédérale de Lausanne, BCH, 1015 Lausanne, Switzerland.

The modulation of spin echoes by homonuclear scalar couplings render the determination of transverse relaxation rates of individual spins difficult, in particular for molecules that are isotopically enriched in (13)C or (15)N, and for all molecules with scalar-coupled protons. To avoid echo modulations, most studies using refocusing pulses have so far been restricted to isolated (1)H, (13)C, or (15)N spins. We report measurements of apparent (1)H transverse relaxation rates of backbone and side-chain protons in Cyclosporin A (CsA) determined by quenching the echo modulations that arise from homonuclear scalar couplings between protons.
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http://dx.doi.org/10.1021/ja907391zDOI Listing
December 2009

Visualization of enantiomers using natural abundant (13)C-filtered single and double quantum selective refocusing experiments: Application to small chiral molecules.

J Magn Reson 2009 Sep 17;200(1):101-8. Epub 2009 Jun 17.

NMR Research Centre, Indian Institute of Science, Bangalore 560012, India.

The routine use of proton NMR for the visualization of enantiomers, aligned in the chiral liquid crystal solvent poly-gamma-benzyl-l-glutamate (PBLG), is restricted due to severe loss of resolution arising from large number of pair wise interaction of nuclear spins. In the present study, we have designed two experimental techniques for their visualization utilizing the natural abundance (13)C edited selective refocusing of single quantum (CH-SERF) and double quantum (CH-DQSERF) coherences. The methods achieve chiral discrimination and aid in the simultaneous determination of homonuclear couplings between active and passive spins and heteronuclear couplings between the excited protons and the participating (13)C spin. The CH-SERF also overcomes the problem of overlap of central transitions of the methyl selective refocusing (SERF) experiment resulting in better chiral discrimination. Theoretical description of the evolution of magnetization in both the sequences has been discussed using polarization operator formalism.
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http://dx.doi.org/10.1016/j.jmr.2009.06.011DOI Listing
September 2009

Simplifying the complex 1H NMR spectra of fluorine-substituted benzamides by spin system filtering and spin-state selection: multiple-quantum-single-quantum correlation.

J Phys Chem A 2008 Oct 30;112(42):10526-32. Epub 2008 Sep 30.

Solid State and Structural Chemistry Unit and NMR Research Centre, Indian Institute of Science, Bangalore 560 012, India.

The proton NMR spectra of fluorine-substituted benzamides are very complex (Figure 1) due to severe overlap of (1)H resonances from the two aromatic rings, in addition to several short and long-range scalar couplings experienced by each proton. With no detectable scalar couplings between the inter-ring spins, the (1)H NMR spectra can be construed as an overlap of spectra from two independent phenyl rings. In the present study we demonstrate that it is possible to separate the individual spectrum for each aromatic ring by spin system filtering employing the multiple-quantum-single-quantum correlation methodology. Furthermore, the two spin states of fluorine are utilized to simplify the spectrum corresponding to each phenyl ring by the spin-state selection. The demonstrated technique reduces spectral complexity by a factor of 4, in addition to permitting the determination of long-range couplings of less than 0.2 Hz and the relative signs of heteronuclear couplings. The technique also aids the judicious choice of the spin-selective double-quantum-single-quantum J-resolved experiment to determine the long-range homonuclear couplings of smaller magnitudes.
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http://dx.doi.org/10.1021/jp8055174DOI Listing
October 2008

Separation and complete analyses of the overlapped and unresolved 1H NMR spectra of enantiomers by spin selected correlation experiments.

J Phys Chem A 2008 Jun 30;112(25):5658-69. Epub 2008 May 30.

Solid State and Structural Chemistry Unit, Indian Institute of Science, Bangalore 560 012, India.

NMR spectroscopic discrimination of optical enantiomers is most often carried out using (2)H and (13)C spectra of chiral molecules aligned in a chiral liquid crystalline solvent. The use of proton NMR for such a purpose is severely hindered due to the spectral complexity and the significant loss of resolution arising from numerous short- and long-distance couplings and the indistinguishable overlap of spectra from both R and S enantiomers. The determination of all the spectral parameters by the analyses of such intricate NMR spectra poses challenges, such as, unraveling of the resonances for each enantiomer, spectral resolution, and simplification of the multiplet pattern. The present study exploits the spin state selection achieved by the two-dimensional (1)H NMR correlation of selectively excited isolated coupled spins (Soft-COSY) of the molecules to overcome these problems. The experiment provides the relative signs and magnitudes of all of the proton-proton couplings, which are otherwise not possible to determine from the broad and featureless one-dimensional (1)H spectra. The utilization of the method for quantification of enantiomeric excess has been demonstrated. The studies on different chiral molecules, each having a chiral center, whose spectral complexity increases with the increasing number of interacting spins, and the advantages and limitations of the method over SERF and DQ-SERF experiments have been reported in this work.
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http://dx.doi.org/10.1021/jp7102462DOI Listing
June 2008

Spin state selective coherence transfer: a method for discrimination and complete analyses of the overlapped and unresolved 1H NMR spectra of enantiomers.

J Magn Reson 2008 May 12;192(1):101-11. Epub 2008 Feb 12.

Solid State and Structural Chemistry Unit, Indian Institute of Science, Bangalore 560 012, India.

In general, the proton NMR spectra of chiral molecules aligned in the chiral liquid crystalline media are broad and featureless. The analyses of such intricate NMR spectra and their routine use for spectral discrimination of R and S optical enantiomers are hindered. A method is developed in the present study which involves spin state selective two dimensional correlation of higher quantum coherence to its single quantum coherence of a chemically isolated group of coupled protons. This enables the spin state selective detection of proton single quantum transitions based on the spin states of the passive nuclei. The technique provides the relative signs and magnitudes of the couplings by overcoming the problems of enantiomer discrimination, spectral complexity and poor resolution, permitting the complete analyses of the otherwise broad and featureless spectra. A non-selective 180 degrees pulse in the middle of MQ dimension retains all the remote passive couplings. This accompanied by spin selective MQ-SQ conversion leads to spin state selective coherence transfer. The removal of field inhomogeneity contributes to dramatically enhanced resolution. The difference in the cumulative additive values of chemical shift anisotropies and the passive couplings, between the enantiomers, achieved by detecting Nth quantum coherence of N magnetically equivalent spins provides enhanced separation of enantiomer peaks. The developed methodology has been demonstrated on four different chiral molecules with varied number of interacting spins, each having a chiral centre.
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http://dx.doi.org/10.1016/j.jmr.2008.02.005DOI Listing
May 2008

Binuclear spin state selective detection of 1H single quantum transitions using triple quantum coherence: a novel method for enantiomeric discrimination.

J Magn Reson 2008 May 12;192(1):92-100. Epub 2008 Feb 12.

Solid State and Structural Chemistry Unit, Indian Institute of Science, Bangalore, Karnataka 560 012, India.

In the present work a novel methodology is developed for the unambiguous discrimination of enantiomers aligned in chiral liquid crystalline media and the simultaneous determination of 1H-1H and 13C-1H couplings in a single experiment. An INEPT transfer and back transfer of magnetization to protons retain the 13C edited 1H magnetization which is utilized to generate spin selective homonuclear triple quantum coherence of dipolar coupled methyl protons. Spin selective correlation of triple quantum to single quantum coherence results in spin state selective detection by 13C spin and the remaining passive protons. The difference between the successive transitions in the triple quantum dimension pertains to sum of the passive couplings and results in enhanced resolution by a factor of three. This results in unambiguous chiral visualization. The masked 13C satellite transitions in the single quantum spectrum are extracted for chiral discrimination. The technique retains all the passive homo- and heteronuclear couplings in the triple quantum dimension by the application of non-selective refocusing pulse on 1H as well as on 13C spins. This, however, refocuses the chemical shift evolution in the triple quantum dimension, and also overcomes the problem of field inhomogeneity. The method enables the determination of spectral information which is otherwise not possible to derive from the broad and featureless proton spectra. The elegant experimental technique has been demonstrated on different chiral molecules.
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http://dx.doi.org/10.1016/j.jmr.2008.02.006DOI Listing
May 2008

Chemical shift anisotropy edited complete unraveling of overlapped 1H NMR spectra of enantiomers: application to small chiral molecules.

J Magn Reson 2008 Apr 5;191(2):259-66. Epub 2008 Jan 5.

Solid State and Structural Chemistry Unit, Indian Institute of Science, SIF, Bangalore, Karnataka 560012, India.

The differential values of NMR spectral parameters like chemical shift anisotropies, dipolar couplings and quadrupolar couplings of enantiomers in chiral liquid crystalline media are employed not only for their visualization but also for their quantification. Large differences in chemical shift anisotropies and the quadrupolar couplings between the enantiomers enable the use of 13C and extensive 2H NMR detection for such a purpose. In spite of high magnetic moment, high sensitivity and abundant presence of protons in all the chiral molecules, 1H detection is not routinely employed due to severe overlap of unresolved transitions arising from short and long distance couplings. Furthermore, the doubling of the spectra from two enantiomers and their indistinguishable overlap due to negligible difference in chemical shift anisotropies hampers their discrimination. The present study demonstrates the use of proton chemical shift anisotropy as an exclusive parameter for such a discrimination. The method employs the non-selective excitation of homonuclear Nth quantum coherence of N coupled protons. The simultaneous flipping of all the coupled spins results in a single transition in the multiple quantum dimension at the cumulative sum of their anisotropic chemical shifts for each enantiomer, with the measurable difference between them, resulting in their complete unraveling.
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http://dx.doi.org/10.1016/j.jmr.2007.12.019DOI Listing
April 2008

Spin selective multiple quantum NMR for spectral simplification, determination of relative signs, and magnitudes of scalar couplings by spin state selection.

J Chem Phys 2007 Dec;127(21):214510

Solid State and Structural Chemistry Unit, Indian Institute of Science, Bangalore 560012, India.

In the present work we demonstrate a novel method for spectral simplification and determination of the relative signs of the scalar couplings using a spin selective multiple quantum NMR experiment. A spin selective excitation of double quantum coherence of A and M spins in a weakly coupled three spin system of the type AMX, results in a doublet in the double quantum dimension whose separation corresponds to the sum of couplings of the active spins to the passive spin X. One component of the doublet has the passive spin X in mid R:alpha state while the other component has the passive spin X in mid R:beta state. The spin selective conversion of double quantum coherence to single quantum coherence does not disturb the spin states of the passive spin thereby providing the spin state selection. There will be two domains of single quantum transitions in single quantum dimension at the chemical shift positions of A and M spins. The mid R:alpha domain of A spin is a doublet because of mid R:alpha and mid R:beta states of M spin only, while that of mid R:beta domain is another doublet in a different cross section of the spectra. The scalar coupling J(AM) can be extracted from any of the mid R:alpha and mid R:beta domain transitions while the relative displacements of the two doublets between the two domains at the two chemical shifts provides the magnitude and sign of the scalar coupling J(AX) relative to the coupling J(MX). Similar result is obtained for zero quantum studies on AMX spin system. The proposed technique is discussed theoretically using product operator approach. The new spin state selective double quantum J-resolved sequence has also been developed. The methodology is confirmed experimentally on a homonuclear weakly coupled three spin system and applied to two different heteronuclear five spin systems.
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http://dx.doi.org/10.1063/1.2803900DOI Listing
December 2007

Enantiomeric discrimination by double quantum excited selective refocusing (DQ-SERF) experiment.

J Phys Chem B 2007 Nov 11;111(43):12403-10. Epub 2007 Oct 11.

Solid State and Structural Chemistry Unit and NMR Research Centre, Indian Institute of Science, Bangalore 560 012, India.

The differences in chemical shift anisotropies, dipolar couplings, and quadrupolar couplings of two enantiomers in the chiral liquid crystalline media are employed to visualize enantiomers. In spite of the fact that proton has high magnetic moment and is abundantly present in all the chiral molecules, 1H NMR is not exploited to its full potential because of severe overlap of unresolved transitions arising from long- and short-distance couplings. Furthermore, the two spectra from R and S enantiomers result in doubling of the number of observable transitions. The present study demonstrates the application of the selectively excited homonuclear double quantum (DQ) coherence correlated to its single quantum coherence of an isolated methyl group in a chiral molecule. The DQ dimension retains only the passive couplings within the protons of the methyl group while the long-distance passive couplings are refocused, removing the overlap of central transitions, and each enantiomer displays a doublet instead of a triplet unlike in regular selective refocusing experiment. The doublet separation being different for each enantiomer results in their discrimination. The cross section taken along the single quantum dimension pertaining to each transition in the DQ dimension provides the one-dimensional spectra for each individual enantiomer with the complete removal of the overlapped transitions from the other enantiomer. The experiment is robust, the pulse sequence is easy to implement, and the methodology has been demonstrated on different chiral molecules.
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http://dx.doi.org/10.1021/jp074873sDOI Listing
November 2007
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