31 results on '"Harish Jangra"'
Search Results
2. Radical chain monoalkylation of pyridines†
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Harish Jangra, Kleni Mulliri, Fabrice Dénès, Philippe Renaud, Samuel Rieder, Camilo Meléndez, and Hendrik Zipse
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chemistry.chemical_classification ,010405 organic chemistry ,Alkene ,Radical ,General Chemistry ,010402 general chemistry ,01 natural sciences ,Medicinal chemistry ,Enol ,3. Good health ,0104 chemical sciences ,Lepidine ,chemistry.chemical_compound ,Hydroboration ,Chemistry ,Reaction rate constant ,chemistry ,Catecholborane ,Alkyl - Abstract
The monoalkylation of N-methoxypyridinium salts with alkyl radicals generated from alkenes (via hydroboration with catecholborane), alkyl iodides (via iodine atom transfer) and xanthates is reported. The reaction proceeds under neutral conditions since no acid is needed to activate the heterocycle and no external oxidant is required. A rate constant for the addition of a primary radical to N-methoxylepidinium >107 M−1 s−1 was experimentally determined. This rate constant is more than one order of magnitude larger than the one measured for the addition of primary alkyl radicals to protonated lepidine demonstrating the remarkable reactivity of methoxypyridinium salts towards radicals. The reaction has been used for the preparation of unique pyridinylated terpenoids and was extended to a three-component carbopyridinylation of electron-rich alkenes including enol esters, enol ethers and enamides., N-Methoxypyridinium salts are exceptionally reactive radical traps that can be used in efficient radical chain reactions with organoboranes.
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- 2021
3. Detour matrix-based adjacent path eccentric distance sum indices for QSAR/QSPR. Part I: development and evaluation.
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Monika Singh 0003, Harish Jangra, Prasad V. Bharatam, and A. K. Madan
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- 2014
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4. Stereoselective and Stereospecific Triflate‐Mediated Intramolecular Schmidt Reaction: Ready Access to Alkaloid Skeletons**
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Philippe Renaud, Hendrik Zipse, Remo Arnold, Robin Marc Schärer, Ajoy Kapat, Harish Jangra, Florence Giornal, Erich Nyfeler, and Lars Gnägi
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Stereochemistry ,alkaloids ,010402 general chemistry ,01 natural sciences ,azides ,Catalysis ,chemistry.chemical_compound ,Stereospecificity ,540 Chemistry ,Schmidt reaction ,Azepine ,Racemization ,Research Articles ,azabicyclic compounds ,010405 organic chemistry ,stereochemistry ,Iminium ,General Chemistry ,General Medicine ,Alkaloid Synthesis ,0104 chemical sciences ,3. Good health ,chemistry ,Intramolecular force ,570 Life sciences ,biology ,Stereoselectivity ,Azide ,Research Article - Abstract
The stereoselectivity and stereospecificity of the triflate‐mediated intramolecular Schmidt reaction of substituted 3‐(1‐azidocyclohexyl)propanol derivatives leading to octahydro‐1H‐pyrrolo[1,2‐a]azepine, the structural skeleton of several important families of alkaloids such as the Stemona alkaloids, has been examined. The reaction involves an initial intramolecular SN2 reaction between the azide moiety and the triflate affording an intermediate spirocyclic aminodiazonoium salt that undergoes the expected 1,2‐shift/N2‐elimination followed by hydride‐mediated iminium salt reduction. Remarkably, chiral alcohols are converted to the azabicyclic derivative with no or limited racemization. The initial asymmetric alcohol center controls the diastereoselectivity of the whole process, leading to the formation of one out of the four possible diastereoisomers of disubstituted octahydro‐1H‐pyrrolo[1,2‐a]azepine. The origin of the stereoselectivity is rationalized based on theoretical calculations. The concise synthesis of (−)‐(cis)‐3‐propylindolizidine and (−)‐(cis)‐3‐butyllehmizidine, two alkaloids found in the venom of workers of the ant Myrmicaria melanogaster, is reported., Enantiomerically enriched azabicyclic compounds found in several important families of alkaloids can be prepared by a remarkably stereospecific and stereoselective intramolecular Schmidt reaction. The initial asymmetric alcohol center controls the whole process, leading to the formation of one out of up to four possible diastereoisomers with inversion of the configuration at the original asymmetric center.
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- 2021
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5. Fourth generation detour matrix-based topological indices for QSAR/QSPR - Part-1: development and evaluation.
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Rakesh Kumar Marwaha, Harish Jangra, Kinkar Chandra Das, Prasad V. Bharatam, and A. K. Madan
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- 2012
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6. A Predictive Model Towards Site‐Selective Metalations of Functionalized Heterocycles, Arenes, Olefins, and Alkanes using TMPZnCl⋅LiCl
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Paul Knochel, Shu‐Mei Yang, Moritz Balkenhohl, Ilya S. Makarov, Hendrik Zipse, and Harish Jangra
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010405 organic chemistry ,Metalation ,Chemistry ,Regioselectivity ,heteroarenes ,General Chemistry ,General Medicine ,010402 general chemistry ,01 natural sciences ,Medicinal chemistry ,Catalysis ,0104 chemical sciences ,amides ,Deprotonation ,Predictive Models ,Site selective ,acidity ,Research Articles ,Research Article ,zinc organometallics - Abstract
The development of a predictive model towards site‐selective deprotometalation reactions using TMPZnCl⋅LiCl is reported (TMP=2,2,6,6‐tetramethylpiperidinyl). The pK a values of functionalized N‐, S‐, and O‐heterocycles, arenes, alkenes, or alkanes were calculated and compared to the experimental deprotonation sites. Large overlap (>80 %) between the calculated and empirical deprotonation sites was observed, showing that thermodynamic factors strongly govern the metalation regioselectivity. In the case of olefins, calculated frozen state energies of the deprotonated substrates allowed a more accurate prediction. Additionally, various new N‐heterocycles were analyzed and the metalation regioselectivities rationalized using the predictive model., Metalation site prediction: The use of simple pK a calculations allowed a reliable prediction of metalation sites in various heterocycles, arenes, olefins, and alkanes, employing the mild base TMPZnCl⋅LiCl. Using this predictive model, also unexplored N‐heterocycles were investigated, and the obtained deprotonation sites rationalized readily.
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- 2020
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7. Molekül‐induzierte Radikalbildung – eine Neubewertung
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Harish Jangra, Hendrik Zipse, and L. Sandhiya
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Chemistry ,General Medicine - Published
- 2020
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8. Construction of α,α‐disubstituted α‐Amino Acid Derivatives via aza‐Morita‐Baylis‐Hillman Reactions of 2‐Aminoacrylates with Activated Olefins
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Harish Jangra, Heng Yi, Qin Xu, Tian‐Yu Wang, Hou-Ze Gui, Yin Wei, Min Shi, Ben Mao, and Hendrik Zipse
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Inorganic Chemistry ,chemistry.chemical_classification ,010405 organic chemistry ,Chemistry ,Organic Chemistry ,Physical and Theoretical Chemistry ,010402 general chemistry ,01 natural sciences ,Medicinal chemistry ,Catalysis ,0104 chemical sciences ,Amino acid - Abstract
A useful and convenient strategy for the synthesis of α,α‐disubstituted α‐amino acid (α‐AA) derivatives via aza‐Morita‐Baylis‐Hillman reaction of 2‐aminoacrylates with activated olefins has been developed. A variety of α‐AA derivatives containing an α‐amino tertiary center were synthesized in good to excellent yields. The kinetic profiles and calculated methyl anion affinity (MAA) values were employed to rationalize the reactivities of different Michael acceptors used in the reaction.
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- 2020
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9. Reliable Functionalization of 5,6-Fused Bicyclic N-Heterocycles Pyrazolopyrimidines and Imidazopyridazines via Zinc and Magnesium Organometallics
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Saroj Kumar Rout, Agonist Kastrati, Harish Jangra, Kuno Schwärzer, Alisa S. Sunagatullina, Maximilien Garny, Fabio Lima, Cara E. Brocklehurst, Konstantin Karaghiosoff, Hendrik Zipse, and Paul Knochel
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Zinc ,Pyrimidines ,Organic Chemistry ,Indicators and Reagents ,Magnesium ,General Chemistry ,Catalysis - Abstract
DFT-calculations allow prediction of the reactivity of uncommon N-heterocyclic scaffolds of pyrazolo[1,5-a]pyrimidines and imidazo[1,2-b]pyridazines and considerably facilitate their functionalization. The derivatization of these N-heterocycles was realized using Grignard reagents for nucleophilic additions to 5-chloropyrazolo[1,5-a]pyrimidines and TMP
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- 2022
10. Reactivities of allenic and olefinic Michael acceptors towards phosphines
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Feng An, Harish Jangra, Yin Wei, Min Shi, Hendrik Zipse, and Armin R. Ofial
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Materials Chemistry ,Metals and Alloys ,Ceramics and Composites ,General Chemistry ,Catalysis ,Surfaces, Coatings and Films ,Electronic, Optical and Magnetic Materials - Abstract
The kinetics of the reactions of tributylphosphine with allenic and olefinic Michael acceptors in dichloromethane at 20 °C was followed by photometric and NMR spectroscopic methods. Combination with DFT-calculated methyl anion affinities revealed the relevance of retroaddition barriers in phosphine-catalysed reactions when mixtures of allenic and olefinic substrates are used.
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- 2022
11. Phosphine-catalyzed [3 + 2] annulation of 2-aminoacrylates with allenoates and mechanistic studies
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Min Shi, Yin Wei, Xiao-Yun Wu, Hou-Ze Gui, Hendrik Zipse, and Harish Jangra
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chemistry.chemical_compound ,Annulation ,Chemistry ,Combinatorial chemistry ,Catalysis ,Phosphine ,Stereocenter - Abstract
A convenient and efficient strategy for the synthesis of 3-pyrrolines containing an amino quaternary stereogenic center via phosphine-catalyzed formal [3 + 2] annulation of 2-aminoacrylates with allenoates is disclosed. A wide range of substrates underwent this reaction smoothly, affording a series of 3-pyrrolines in good to excellent yields, and it could be extended to a gram-scale reaction. The kinetic profiles and the calculated methyl anion affinity (MAA) values were employed to explain the reactivities of different allenoates used in the reaction, which provides deep understanding for the catalytic mechanism of this type of reaction.
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- 2020
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12. Ferrocenes with a Persulfurated Cyclopentadienyl Ring: Synthesis, Structural Studies, and Optoelectronic Properties
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Harish Jangra, Konstantin Karaghiosoff, Peter M. Zehetmaier, Tobias Blockhaus, Karlheinz Sünkel, Fabian L. Zott, and Christian Klein-Heßling
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010405 organic chemistry ,Metalation ,Chemistry ,Communication ,Organic Chemistry ,Intermolecular force ,metalation ,General Chemistry ,Crystal structure ,metallocenes ,010402 general chemistry ,Ring (chemistry) ,Electrochemistry ,01 natural sciences ,Communications ,Catalysis ,persulfurated arenes ,X-ray diffraction ,0104 chemical sciences ,Crystallography ,Cyclopentadienyl complex ,Intramolecular force ,X-ray crystallography - Abstract
Persulfurated arenes are a fascinating class of functional molecules with a wide range of potential applications. Ferrocenes are also a multifaceted class of aromatic compounds that can easily be finetuned for an enormous variety of desired properties. A combination of both substance classes might yield an even wider field of applications. Herein, we describe the synthesis of two ferrocenes with one persulfurated cyclopentadienyl ring [C5(SR)5], with R=Me or Ph, together with their crystal structures, optical, and electrochemical properties. Both crystal structures show significant intramolecular sulfur‐iron interactions as well as weak intermolecular sulfur– contacts. Cyclovoltammetry of the [C5(SPh)5] compound shows a high oxidation potential of 651 mV vs. FcH/FcH+., Metalation: Ferrocenes with one persulfurated cyclopentadienyl ring [C5(SR)5]FeCp have been prepared from monobromoferrocene by a sequence of deprotonations and electrophilic thiolations. In their crystal structures, all cyclopentadienyl rings have their thiolate substituents in axial positions away from the iron atom. Cyclovoltammetric studies show that the sulfur substituents lead to significantly enhanced oxidative stability (see figure).
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- 2019
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13. Lewis‐Säure‐dirigierte regioselektive Metallierungen an Pyridazin
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Marian Ebeling, Moritz Balkenhohl, Konstantin Karaghiosoff, Paul Knochel, Harish Jangra, Hendrik Zipse, and Tobias Lenz
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Chemistry ,General Medicine - Published
- 2019
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14. Lewis Acid Directed Regioselective Metalations of Pyridazine
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Marian Ebeling, Moritz Balkenhohl, Paul Knochel, Harish Jangra, Konstantin Karaghiosoff, Tobias Lenz, and Hendrik Zipse
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Denticity ,010405 organic chemistry ,Metalation ,Regioselectivity ,chemistry.chemical_element ,General Chemistry ,010402 general chemistry ,01 natural sciences ,Medicinal chemistry ,Catalysis ,Frustrated Lewis pair ,0104 chemical sciences ,Pyridazine ,chemistry.chemical_compound ,chemistry ,Lewis acids and bases ,Boron - Abstract
Mono- or bidentate boron Lewis acids trigger a regioselective magnesiation or zincation of pyridazine in position C3 (ortho product) or C4 (meta product). The regioselectivity of the metalation was rationalized with the help of calculated pKa values of both pyridazine and pyridazine/Lewis acid complexes.
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- 2019
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15. Stereoselective and Stereospecific Triflate Mediated Intramolecular Schmidt Reaction: Easy Access to Alkaloid Skeletons
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Florence Giornal, Remo Arnold, Lars Gnägi, Harish Jangra, Robin Marc Schärer, Ajoy Kapat, Hendrik Zipse, Erich Nyfeler, and Philippe Renaud
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chemistry.chemical_compound ,Stereospecificity ,chemistry ,Stereochemistry ,Intramolecular force ,Iminium ,Schmidt reaction ,Stereoselectivity ,Azide ,Azepine ,Trifluoromethanesulfonate - Abstract
The stereoselectivity and stereospecificity of the triflate mediated intramolecular Schmidt reaction of substituted 3-(1-azidocyclohexyl)propanol derivatives leading to octahydro-1H-pyrrolo[1,2-a]azepine, the structural skeleton of several important families of alkaloids such as the Stemona alkaloids, has been examined. The reaction involves an initial intramolecular SN2 reaction between the azide moiety and the triflate affording an intermediate spirocyclic aminodiazonoium salt that undergoes the expected 1,2-shift/N2-elimination followed by hydride mediated iminium salt reduction. Remarkably, chiral alcohols are converted to the azabicylic derivative with no or limited racemization. The initial asymmetric alcohol center controls the diastereoselectivity of the whole process leading to the formation of one out of the four possible diastereoisomers of disubstituted octahydro-1H-pyrrolo[1,2-a]azepine. The origin of the stereoselectivity is rationalized based on theoretical calculations. The concise synthesis of (–)-(cis)-3-propylindolizidine and (–)-(cis)-3-butyllehmizidine, two alkaloids found in the venom of workers of the ant Myrmicaria melanogaster, is reported.
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- 2020
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16. Stereochemical Control of the Triflate Mediated Intramolecular Schmidt Reaction
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Lars Gnägi, Florence Giornal, Harish Jangra, Ajoy Kapat, Erich Nyfeler, Hendrik Zipse, Robin Marc Schärer, and Philippe Renaud
- Abstract
The stereoselectivity of the triflate mediated intramolecular Schmidt reaction of substituted 3-(1-azidocyclohexyl)propanol derivatives leading to octahydro-1H-pyrrolo[1,2-a]azepine, the structural skeleton of several important families of alkaloids such as the Stemona alkaloids, has been examined. The reaction involves an initial intramolecular SN2 reaction between the azide moiety and the triflate affording an intermediate spirocyclic aminodiazonoium salt that undergoes the expected 1,2-shift/N2-elimination followed by hydride mediated iminium salt reduction. Remarkably, chiral alcohols are converted to the azabicylic derivative with no or limited racemization. The initial asymmetric alcohol center controls the diastereoselectivity of the whole process leading to the formation of one out of the four possible diastereoisomers of disubstituted octahydro-1H-pyrrolo[1,2-a]azepine. The origin of the stereoselectivity of is rationalized based on theoretical calculations.
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- 2020
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17. Quantification and Theoretical Analysis of the Electrophilicities of Michael Acceptors
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Quan Chen, Hendrik Zipse, Haruyasu Asahara, Harish Jangra, Herbert Mayr, Armin R. Ofial, Zhen Li, and Dominik S. Allgäuer
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chemistry.chemical_classification ,010405 organic chemistry ,Stereochemistry ,Sulfonium ,Kinetics ,General Chemistry ,010402 general chemistry ,01 natural sciences ,Biochemistry ,Medicinal chemistry ,Catalysis ,0104 chemical sciences ,Ion ,chemistry.chemical_compound ,Colloid and Surface Chemistry ,Reaction rate constant ,chemistry ,Nucleophile ,Ylide ,Electrophile ,Pyridinium - Abstract
In order to quantify the electrophilic reactivities of common Michael acceptors, we measured the kinetics of the reactions of monoacceptor-substituted ethylenes (H2C═CH-Acc, 1) and styrenes (PhCH═CH-Acc, 2) with pyridinium ylides 3, sulfonium ylide 4, and sulfonyl-substituted chloromethyl anion 5. Substitution of the 57 measured second-order rate constants (log k) and the previously reported nucleophile-specific parameters N and sN for 3–5 into the correlation log k = sN(E + N) allowed us to calculate 15 new empirical electrophilicity parameters E for Michael acceptors 1 and 2. The use of the same parameters sN, N, and E for these different types of reactions shows that all reactions proceed via a common rate-determining step, the nucleophilic attack of 3–5 at the Michael acceptors with formation of acyclic intermediates, which subsequently cyclize to give tetrahydroindolizines (stepwise 1,3-dipolar cycloadditions with 3) and cyclopropanes (with 4 and 5), respectively. The electrophilicity parameters E th...
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- 2017
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18. Path Pendeccentric Connectivity Indices: Detour Matrix Based Molecular Descriptors for QSAR/QSPR Studies, Part 1
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Harish Jangra, A. K. Madan, and Naveen Khatri
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Matrix (mathematics) ,Quantitative structure–activity relationship ,Development (topology) ,Molecular descriptor ,Path (graph theory) ,Biological system ,Mathematics - Abstract
In the present study, highly sensitive detour matrix based molecular descriptors (MDs) termed as path pendeccentric connectivity indices 1-4 as well as their topochemical variants have been conceptualized. Proposed MDs are unique because they simultaneously take into consideration the cyclicity, path pendenticity, path eccentricity and augmented adjacency of each vertex in a hydrogen depleted molecular structure. An in-house computer program was also developed to calculate values of proposed MDs. Proposed MDs were evaluated for degeneracy, discriminating power, sensitivity towards relative position of substituent(s) in cyclic structures, branching and correlation with existing MDs. Highly encouraging results offer proposed MDs a vast potential for similarity/dissimilarity studies, characterization of structures, combinatorial library design, lead identification/optimization, pharmacokinetic relationship studies and QSAR/QSPR/QSTR studies. Proposed MDs will also take due care of shape factor, relative position (s) and presence of hetero atoms in chemical structures.
- Published
- 2017
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19. Assessing therapeutic potential of molecules: molecular property diagnostic suite for tuberculosis $$(\mathbf{MPDS}^{\mathbf{TB}})$$ ( MPDS TB )
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Subramanian Venkatesan, Neeraj Kumar Rajput, Pankaj Narang, Aparna Singh, Prasun Dutta, D Arun Kumar, Karunakar Tanneeru, Anurag Passi, Anshu Bhardwaj, Harish Jangra, Kaamini Raithatha, Uca Jaleel, Anamika Singh Gaur, Prasad V. Bharatam, G. Narahari Sastry, Anmol J. Hemrom, Ruchi Mishra, S Hemasri, Deepak R. Bharti, Gajendra Ps Raghava, Yogesh M. Joshi, Hari Sailaja, Rakesh Kumar, P Sri Saranya, Suresh Kumar, M Prasanthi, Deepak Pandit, Kumardeep Chaudhary, N Yedukondalu, M. Karthikeyan, R. Venkata Krishnan, Sridhara Janardhan, Devesh Kumar, M Ram Vivek, Neha Tripathi, E. R. Azhagiya Singam, Reetu Sharma, Asheesh Kumar, R Srinithi, Lijo John, Chinmayee Choudhury, Andrew M. Lynn, Arun Sharma, Abhaysinh Mori, Nandan Kumar, Vijay M. Khedkar, Charuvaka Muvva, Sandeep Singh, Chinmai Madhuri, and Anirban Banerji
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0301 basic medicine ,Discrete mathematics ,Computer science ,Suite ,Nanotechnology ,General Chemistry ,File format ,01 natural sciences ,0104 chemical sciences ,Autodock vina ,010404 medicinal & biomolecular chemistry ,03 medical and health sciences ,030104 developmental biology ,Open source ,Molecular property ,Data library ,Model development ,Protein target - Abstract
Molecular Property Diagnostic Suite ( $$\text {MPDS}^{\mathrm{TB}}$$ ) is a web tool ( http://mpds.osdd.net ) designed to assist the in silico drug discovery attempts towards Mycobacterium tuberculosis (Mtb). $$\text {MPDS}^{\mathrm{TB}}$$ tool has nine modules which are classified into data library (1–3), data processing (4–5) and data analysis (6–9). Module 1 is a repository of literature and related information available on the Mtb. Module 2 deals with the protein target analysis of the chosen disease area. Module 3 is the compound library consisting of 110.31 million unique molecules generated from public domain databases and custom designed search tools. Module 4 contains tools for chemical file format conversions and 2D to 3D coordinate conversions. Module 5 helps in calculating the molecular descriptors. Module 6 specifically handles QSAR model development tools using descriptors generated in the Module 5. Module 7 integrates the AutoDock Vina algorithm for docking, while module 8 provides screening filters. Module 9 provides the necessary visualization tools for both small and large molecules. The workflow-based open source web portal, $$\text {MPDS}^{\mathrm{TB}}$$ 1.0.1 can be a potential enabler for scientists engaged in drug discovery in general and in anti-TB research in particular. SYNOPSIS: A web-based $$\text {MPDS}^{\mathrm{TB}}$$ Galaxy tool is developed for assessing therapeutic potential of molecules. $$\text {MPDS}^{\mathrm{TB}}$$ is categorized into Data Library, Data Processing and Data Analysis. It can be a potential enabler for scientists engaged in drug discovery in general and in anti-TB research in particular.
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- 2017
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20. Molecule-Induced Radical Formation (MIRF) Reactions-A Reappraisal
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Harish Jangra, Hendrik Zipse, and L. Sandhiya
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Reaction mechanism ,010405 organic chemistry ,Chemistry ,Radical ,radical formation ,Minireviews ,General Chemistry ,010402 general chemistry ,Photochemistry ,01 natural sciences ,Redox ,Catalysis ,0104 chemical sciences ,Mirf ,reaction mechanisms ,Thermochemistry ,Molecule ,Radical formation ,thermochemistry ,Minireview ,Chain reaction - Abstract
Radical chain reactions are commonly initiated through the thermal or photochemical activation of purpose‐built initiators, through photochemical activation of substrates, or through well‐designed redox processes. Where radicals come from in the absence of these initiation strategies is much less obvious and are often assumed to derive from unknown impurities. In this situation, molecule‐induced radical formation (MIRF) reactions should be considered as well‐defined alternative initiation modes. In the most general definition of MIRF reactions, two closed‐shell molecules react to give a radical pair or biradical. The exact nature of this transformation depends on the σ‐ or π‐bonds involved in the MIRF process, and this Minireview specifically focuses on reactions that transform two σ‐bonds into two radicals and a closed‐shell product molecule., Where radicals come from: Molecule‐induced radical formation (MIRF) processes, where one closed‐shell molecule helps another one dissociate, are viable alternatives for simple unimolecular homolytic bond breaking events.
- Published
- 2019
21. Conformational Preferences in Small Peptide Models: The Relevance ofcis/trans-Conformations
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Harish Jangra, Ruth M. Gschwind, Johnny Hioe, Hendrik Zipse, Michael H. Haindl, and Florian Achrainer
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Models, Molecular ,Magnetic Resonance Spectroscopy ,Protein Conformation ,Implicit solvation ,010402 general chemistry ,01 natural sciences ,Catalysis ,Structure-Activity Relationship ,chemistry.chemical_compound ,Protein structure ,Isomerism ,Computational chemistry ,0103 physical sciences ,Computer Simulation ,Dimethyl Sulfoxide ,Conformational isomerism ,Dipeptide ,010304 chemical physics ,Chemistry ,Organic Chemistry ,Dipeptides ,General Chemistry ,Protein structure prediction ,0104 chemical sciences ,Crystallography ,Thermodynamics ,Protein folding ,Two-dimensional nuclear magnetic resonance spectroscopy ,Cis–trans isomerism - Abstract
The accurate description of cis/trans peptide structures is of fundamental relevance for the field of protein modeling and protein structure determination. A comprehensive conformational analysis of dipeptide model Ace-Gly-NMe (1) has been carried out by using a combination of theoretical calculations and experimental ((1) H and (13) C NMR and NOESY) spectroscopic measurements to assess the relevance of cis-peptide conformers. NMR measurements in dimethyl sulfoxide (DMSO) solution and calculations employing a continuum solvation model both point to the extended trans,trans conformer C5_tt as the global minimum. The cis-peptide structures C5_ct and C5_tc, with the N- or C-terminal amide group in cis-conformation, are observed separately and located 13.0±2 kJ mol(-1) higher in energy. This is in close agreement with the theoretical prediction of around 12 kJ mol(-1) in DMSO. The ability of common protein force fields to reproduce the energies of the cis-amide conformers C5_ct and C5_tc in 1 is limited, making these methods unsuitable for the description of cis-peptide structures in protein simulations.
- Published
- 2016
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22. Nucleophilicity and Electrophilicity Parameters for Predicting Absolute Rate Constants of Highly Asynchronous 1,3-Dipolar Cycloadditions of Aryldiazomethanes
- Author
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Harish Jangra, Elina Fuks, Peter Mayer, Quan Chen, Ivo Zenz, Hendrik Zipse, Armin R. Ofial, and Herbert Mayr
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010405 organic chemistry ,Chemistry ,Kinetics ,General Chemistry ,010402 general chemistry ,01 natural sciences ,Biochemistry ,Catalysis ,0104 chemical sciences ,Ion ,chemistry.chemical_compound ,Colloid and Surface Chemistry ,Reaction rate constant ,Nucleophile ,Computational chemistry ,Electrophile ,Diazo ,Spectroscopy ,Dichloromethane - Abstract
Kinetics of the reactions of aryldiazomethanes (ArCHN2) with benzhydrylium ions (Ar2CH+) have been measured photometrically in dichloromethane. The resulting second-order rate constants correlate linearly with the electrophilicities E of the benzhydrylium ions which allowed us to use the correlation lg k = sN(N + E) (eq 1) for determining the nucleophile-specific parameters N and sN of the diazo compounds. UV–vis spectroscopy was analogously employed to measure the rates of the 1,3-dipolar cycloadditions of these aryldiazomethanes with acceptor-substituted ethylenes of known electrophilicities E. The measured rate constants for the reactions of the diazoalkanes with highly electrophilic Michael acceptors (E > −11, for example 2-benzylidene Meldrum’s acid or 1,1-bis(phenylsulfonyl)ethylene) agreed with those calculated by eq 1 from the one-bond nucleophilicities N and sN of the diazo compounds and the one-bond electrophilicities of the dipolarophiles, indicating that the incremental approach of eq 1 may al...
- Published
- 2018
23. Electrostatic Effects on the Stability of Peptide Radicals
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Hendrik Zipse and Harish Jangra
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Models, Molecular ,Free Radicals ,Protein Conformation ,Radical ,Static Electricity ,Peptide ,02 engineering and technology ,010402 general chemistry ,01 natural sciences ,Stability (probability) ,Ion ,chemistry.chemical_compound ,Chlorides ,Electric field ,Materials Chemistry ,Side chain ,Physical and Theoretical Chemistry ,chemistry.chemical_classification ,Dipeptide ,Glycylglycine ,Protein Stability ,Sodium ,Charge (physics) ,Dipeptides ,021001 nanoscience & nanotechnology ,0104 chemical sciences ,Surfaces, Coatings and Films ,chemistry ,Models, Chemical ,Chemical physics ,Quantum Theory ,Thermodynamics ,0210 nano-technology - Abstract
We explored the influence of external electric fields (EEFs) on the stability of a glycine dipeptide model radical using high-level quantum chemical methods. Remotely located ions (Cl-/Na+) are used to implement EEF effects. The effects of these ions are reproduced using background point charges and oriented EEFs. Remote charges as far as 900 pm from the C-alpha radical center can be significantly stabilizing or destabilizing as a function of their relative orientation. The magnitude of these effects is also strongly dependent on the distance between the radical center and the charge location. After examining the strengths and weaknesses of some frequently used quantum mechanics methods in describing these effects properly, a comparison is made on the stability of dipeptide radicals bearing protonable or deprotonable side chains. In this group, the stability of the respective C-alpha radicals mainly depends on the preferred orientation of the charge-carrying side chain.
- Published
- 2018
24. Unique Stereoselective Homolytic C-O Bond Activation in Diketopiperazine-Derived Alkoxyamines by Adjacent Amide Pyramidalization
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Harish Jangra, Hendrik Zipse, Ivana Císařová, Radek Pohl, Ullrich Jahn, and Tynchtyk Amatov
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Steric effects ,010405 organic chemistry ,Chemistry ,Stereochemistry ,Radical ,Organic Chemistry ,Diastereomer ,General Chemistry ,010402 general chemistry ,01 natural sciences ,Catalysis ,0104 chemical sciences ,Homolysis ,chemistry.chemical_compound ,Amide ,Peptide bond ,Stereoselectivity ,Isomerization - Abstract
Simple monocyclic diketopiperazine (DKP)-derived alkoxyamines exhibit unprecedented activation of a remote C-O bond for homolysis by amide distortion. The combination of strain-release-driven amide planarization and the persistent radical effect (PRE) enables a unique, irreversible, and quantitative trans→cis isomerization under much milder conditions than typically observed for such homolysis-limited reactions. This isomerization is shown to be general and independent of the steric and electronic nature of both the amino acid side chains and the substituents at the DKP nitrogen atoms. Homolysis rate constants are determined, and they significantly differ for both the labile trans diastereomers and the stable cis diastereomers. To reveal the factors influencing this unusual process, structural features of the kinetic trans diastereomers and thermodynamic cis diastereomers are investigated in the solid state and in solution. X-ray crystallographic analysis and computational studies indicate substantial distortion of the amide bond from planarity in the trans-alkoxyamines, and this is believed to be the cause for the facile and quantitative isomerization. Thus, these amino-acid-derived alkoxyamines are the first examples that exhibit a large thermodynamic preference for one diastereomer over the other upon thermal homolysis, and this allows controlled switching of configurations and configurational cycling.
- Published
- 2018
25. Kinetics and Mechanism of Oxirane Formation by Darzens Condensation of Ketones: Quantification of the Electrophilicities of Ketones
- Author
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Quan Chen, Armin R. Ofial, Peter Mayer, Hendrik Zipse, Harish Jangra, Herbert Mayr, and Zhen Li
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010405 organic chemistry ,Epoxide ,Protonation ,General Chemistry ,010402 general chemistry ,01 natural sciences ,Biochemistry ,Medicinal chemistry ,Catalysis ,0104 chemical sciences ,chemistry.chemical_compound ,Colloid and Surface Chemistry ,Deprotonation ,Reaction rate constant ,chemistry ,Nucleophile ,Darzens reaction ,Halohydrin ,Carbanion - Abstract
The kinetics of epoxide formation by Darzens condensation of aliphatic ketones 1 with arylsulfonyl-substituted chloromethyl anions 2 (ArSO2CHCl–) have been determined photometrically in DMSO solution at 20 °C. The reactions proceed via nucleophilic attack of the carbanions at the carbonyl group to give intermediate halohydrin anions 4, which subsequently cyclize with formation of the oxiranes 3. Protonation of the reaction mixture obtained in THF solution at low temperature allowed the intermediates to be trapped and the corresponding halohydrins 4-H to be isolated. Crossover experiments, i.e., deprotonation of the halohydrins 4-H in the presence of a trapping reagent for the regenerated arylsulfonyl-substituted chloromethyl anions 2, provided the relative rates of backward (k–CC) and ring closure (krc) reactions of the intermediates. Combination of the kinetic data (k2exptl) with the splitting ratio (k–CC/krc) gave the second-order rate constants kCC for the attack of the carbanions 2 at the ketones 1. T...
- Published
- 2018
26. Detour Cum Distance Matrix Based Topological Descriptors for QSAR/QSPR Part-I: Development and Evaluation
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Harish Jangra, Anil Kumar Madan, Prasad V. Bharatam, and Monika Gupta
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Quantitative structure–activity relationship ,Development (topology) ,Theoretical computer science ,Distance matrix ,Chemistry ,Drug Discovery ,Pharmaceutical Science ,Molecular Medicine - Published
- 2014
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27. Relative Eccentric Distance Sum/Product Indices for QSAR/QSPR: Development, Evaluation, and Application
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A. K. Madan, Prasad V. Bharatam, Harish Jangra, and Monika Gupta
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Quantitative structure–activity relationship ,Molecular Structure ,Chemistry ,Stereochemistry ,Thiourea ,Quantitative Structure-Activity Relationship ,General Chemistry ,General Medicine ,Aminoacyltransferases ,Branching (polymer chemistry) ,Combinatorics ,Distance matrix ,Moving average ,Position (vector) ,Molecular descriptor ,Product (mathematics) ,Humans ,Degeneracy (mathematics) - Abstract
In the present study, five detour/distance matrix based molecular descriptors (MDs) termed as relative eccentric distance sum/product indices (denoted by Rξ1SV, Rξ2SV, Rξ3SV, RPξ1SV, and RPξ2SV), as well as their topochemical versions denoted by (Rξ1cSV, Rξ2cSV, Rξ3cSV, RPξ1cSV, and RPξ2cSV) have been conceptualized for exclusive use for molecules containing cyclic moieties. The said MDs exhibited exceptionally high discriminating power and high sensitivity toward branching/relative position of substituents in cyclic structures amalgamated with negligible degeneracy. Subsequently, the proposed MDs along with other MDs were successfully utilized for the development of models for the prediction of human glutaminyl cyclase (hQC) inhibitory activity using decision tree (DT), random forest (RF) and moving average analysis (MAA). A data set comprising of 45 analogues of substituted 3-(1H-imidazol-1-yl) propyl thiourea derivatives was used. DT identified proposed relative eccentric distance sum topochemical inde...
- Published
- 2014
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28. Cover Feature: Ferrocenes with a Persulfurated Cyclopentadienyl Ring: Synthesis, Structural Studies, and Optoelectronic Properties (Chem. Eur. J. 55/2019)
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Christian Klein-Heßling, Fabian L. Zott, Harish Jangra, Konstantin Karaghiosoff, Tobias Blockhaus, Karlheinz Sünkel, and Peter M. Zehetmaier
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Crystallography ,Cyclopentadienyl complex ,Metalation ,Chemistry ,Organic Chemistry ,Cover (algebra) ,General Chemistry ,Ring (chemistry) ,Catalysis - Published
- 2019
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29. Formation/Fate of Reactive Metabolites from General Anesthetics and A Comparison of Toxic and Non-Toxic Analogues: A DFT Study
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Prasad V. Bharatam, Vaibhav A. Dixit, Sonam Bhatia, and Harish Jangra
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Chloroform ,Anesthetics, General ,Biochemistry (medical) ,Clinical Biochemistry ,Enthalpy ,Pharmaceutical Science ,Medicinal chemistry ,Bond-dissociation energy ,Catalysis ,chemistry.chemical_compound ,chemistry ,General chemistry ,medicine ,Thermodynamics ,Organic chemistry ,Pharmacology (medical) ,Reactivity (chemistry) ,Phosgene ,Halothane ,medicine.drug - Abstract
Chloroform and Halothane are well known hepatotoxic anesthetics for which toxicity is attributed to their reactive metabolites. The molecular level details of reactions leading to the formation of reactive metabolites from chloroform and halothane have not been explored. Potential energy surface (PES) for the formation of phosgene (a toxic intermediate) from Chloroform has been studied using quantum chemical methods. The HOOH mediated reaction of chloroform to give phosgene has been found to be exothermic by 81.24 kcal/mol with a barrier of ~ 3 kcal/mol through the water catalyzed transition sate. The quantum chemical studies on the reactivity profile of phosgene indicated that urea derivatives need to be considered on the mechanism leading to toxicity. Similarly, metabolic pathways of Halothane oxidation have been studied. The C-H bond dissociation energies (BDE) and radical stabilization energies (RSE) for Chloroform and Halothane (95 kcal/mol and10 kcal/mol) were found to be significantly different for these toxic anesthetics in comparison to their safer analogues (100 kcal/mol and5 kcal/mol) respectively; thus these parameters can be employed to distinguish toxic and non-toxic general anesthetics. Enthalpy for the Cpd I, a widely used model for CYP450 enzymes, mediated reactions also agreed well with these results.
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- 2013
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30. Fourth generation detour matrix-based topological indices for QSAR/QSPR - Part-1: development and evaluation
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Kinkar Chandra Das, Rakesh Kumar Marwaha, Harish Jangra, A. K. Madan, and Prasad V. Bharatam
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Path (topology) ,Quantitative structure–activity relationship ,Reduction (recursion theory) ,Computational Biology ,Quantitative Structure-Activity Relationship ,Randić's molecular connectivity index ,Models, Theoretical ,Topology ,Computer Science Applications ,Combinatorics ,Matrix (mathematics) ,Models, Chemical ,Similarity (network science) ,Position (vector) ,Drug Design ,Drug Discovery ,Combinatorial Chemistry Techniques ,Humans ,Degeneracy (mathematics) ,Software ,Mathematics - Abstract
In the present study, four detour matrix-based Topological Indices (TIs) termed as augmented path eccentric connectivity indices 1-4 (denoted by (AP)ξ(1)(C), (AP)ξ(2)(C), (AP)ξ(3)(C) and (AP)ξ(4)(C)) as well as their topochemical versions (denoted by (AP)ξ(1c)(C), (AP)ξ(2c)(C), (AP)ξ(3c)(C) and (AP)ξ(4c)(C)) have been conceptualised. A modified detour matrix termed as chemical detour matrix (Δ(c)) has also been proposed so as to facilitate computation of index values of topochemical versions of the said TIs. Values of the proposed TIs were computed for all the possible structures containing three, four and five vertices using an in-house computer program. The said TIs exhibited exceptionally high discriminating power and high sensitivity towards branching/relative position of substituent(s) in cyclic structures amalgamated with negligible degeneracy. Due care was taken during the development of TIs so as to ensure that reduction in index values of complex chemical structures to be within reasonable limits without compromising discriminating power. The mathematical properties of one of the proposed TIs have also been studied. With exceptionally high discriminating power, high sensitivity towards branching as well as relative position(s) of substituents in cyclic structures and negligible degeneracy, the proposed indices offer a vast potential for use in characterisation of structures, similarity/dissimilarity studies, lead identification and optimisation, combinatorial library design and quantitative structure-activity/property/toxicity/pharmacokinetic relationship studies.
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- 2012
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31. Fast Microsecond Dynamics of the Protein–Water Network in the Active Site of Human Carbonic Anhydrase II Studied by Solid-State NMR Spectroscopy
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Petra Rovó, Suresh K. Vasa, Lars V. Schäfer, Chandan K. Das, Rasmus Linser, Himanshu Singh, Christopher Päslack, Hendrik Zipse, and Harish Jangra
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Protein Conformation ,Carbonic anhydrase II ,Molecular Dynamics Simulation ,010402 general chemistry ,Carbonic Anhydrase II ,01 natural sciences ,Biochemistry ,Catalysis ,Enzyme catalysis ,Molecular dynamics ,Colloid and Surface Chemistry ,Protein structure ,Catalytic Domain ,Escherichia coli ,Humans ,Nuclear Magnetic Resonance, Biomolecular ,biology ,Chemistry ,Chemical shift ,Relaxation (NMR) ,Water ,Active site ,Hydrogen Bonding ,General Chemistry ,0104 chemical sciences ,Solid-state nuclear magnetic resonance ,biology.protein ,Biophysics ,Protein Binding - Abstract
Protein-water interactions have widespread effects on protein structure and dynamics. As such, the function of many biomacromolecules can be directly related to the presence and exchange of water molecules. While the presence of structural water sites can be easily detected by X-ray crystallography, the dynamics within functional water-protein network architectures is largely elusive. Here we use solid-state NMR relaxation dispersion measurements with a focus on those active-site residues in the enzyme human carbonic anhydrase II (hCAII) that constitute the evolutionarily conserved water pocket, key for CAs' enzymatic catalysis. Together with chemical shifts, peak broadening, and results of molecular dynamics (MD) and DFT shift calculations, the relaxation dispersion data suggest the presence of a widespread fast μs-time-scale dynamics in the pocket throughout the protein-water network. This process is abrogated in the presence of an inhibitor which partially disrupts the network. The time scale of the protein-water pocket motion coincides both with the estimated residence time of Zn-bound water/OH- in the pocket showing the longest lifetimes in earlier magnetic relaxation dispersion experiments as well as with the rate-limiting step of catalytic turnover. As such, the reorganization of the water pocket:enzyme architecture might constitute an element of importance for enzymatic activity of this and possibly other proteins.
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