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Noncovalent Interactions between Trimethylamine N-Oxide (TMAO), Urea, and Water

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    Noncovalent Interactions between Trimethylamine N-Oxide (TMAO), Urea, and Water
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    • Sarah G. Zetterholm
      Sarah G. Zetterholm
      Department of Chemistry and Biochemistry, Mississippi College, P.O. Box 4036, Clinton, Mississippi 39058, United States
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    • Genevieve A. Verville
      Genevieve A. Verville
      Department of Chemistry and Biochemistry, University of Mississippi, P.O. Box 1848, University, Mississippi 38655, United States
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    • Leeann Boutwell
      Leeann Boutwell
      Department of Chemistry and Biochemistry, Mississippi College, P.O. Box 4036, Clinton, Mississippi 39058, United States
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    • Christopher Boland
      Christopher Boland
      Department of Chemistry and Biochemistry, University of Mississippi, P.O. Box 1848, University, Mississippi 38655, United States
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    • John C. Prather
      John C. Prather
      Department of Chemistry and Biochemistry, University of Mississippi, P.O. Box 1848, University, Mississippi 38655, United States
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    • Jonathan Bethea
      Jonathan Bethea
      Department of Chemistry and Biochemistry, Mississippi College, P.O. Box 4036, Clinton, Mississippi 39058, United States
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    • Jordan Cauley
      Jordan Cauley
      Department of Chemistry and Biochemistry, University of Mississippi, P.O. Box 1848, University, Mississippi 38655, United States
      Department of Chemistry and Biochemistry, Mississippi College, P.O. Box 4036, Clinton, Mississippi 39058, United States
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    • Kayla E. Warren
      Kayla E. Warren
      Department of Chemistry and Biochemistry, University of Mississippi, P.O. Box 1848, University, Mississippi 38655, United States
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    • Shelley A. Smith
      Shelley A. Smith
      Department of Chemistry and Biochemistry, Mississippi College, P.O. Box 4036, Clinton, Mississippi 39058, United States
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    • David H. Magers
      David H. Magers
      Department of Chemistry and Biochemistry, Mississippi College, P.O. Box 4036, Clinton, Mississippi 39058, United States
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      Orcidhttp://orcid.org/0000-0002-8822-947X
    • Nathan I. Hammer*
      Nathan I. Hammer
      Department of Chemistry and Biochemistry, University of Mississippi, P.O. Box 1848, University, Mississippi 38655, United States
      *E-mail: [email protected]
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      Orcidhttp://orcid.org/0000-0002-6221-2709
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    The Journal of Physical Chemistry B

    Cite this: J. Phys. Chem. B 2018, 122, 38, 8805–8811
    Click to copy citationCitation copied!
    https://doi.org/10.1021/acs.jpcb.8b04388
    Published August 30, 2018
    Copyright © 2018 American Chemical Society
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    Abstract

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    Trimethylamine N-oxide (TMAO) and urea are two important osmolytes with their main significance to the biophysical field being in how they uniquely interact with proteins. Urea is a strong protein destabilizing agent, whereas TMAO is known to counteract urea’s deleterious effects. The exact mechanisms by which TMAO stabilizes and urea destabilizes folded proteins continue to be debated in the literature. Although recent evidence has suggested that urea binds directly to amino acid side chains to make protein folding less thermodynamically favored, it has also been suggested that urea acts indirectly to denature proteins by destabilizing the surrounding hydrogen bonding water networks. Here, we elucidate the molecular level mechanism of TMAO’s unique ability to counteract urea’s destabilizing nature by comparing Raman spectroscopic frequency shifts to the results of electronic structure calculations of microsolvated molecular clusters. Experimental and computational data suggest that the addition of TMAO into an aqueous solution of urea induces blue shifts in urea’s H-N-H symmetric bending modes, which is evidence for direct interactions between the two cosolvents.

    Copyright © 2018 American Chemical Society

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    Supporting Information

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    The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.jpcb.8b04388.

    • Raman spectra of 4 M aqueous urea compared to an aqueous solution that is 4 M urea and 4 M TMAO (PDF)

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    This article is cited by 24 publications.

    1. Pamina M. Winkler, Cécilia Siri, Johann Buczkowski, Juliana V. C. Silva, Lionel Bovetto, Christophe Schmitt, Francesco Stellacci. Modulating Weak Protein–Protein Cross-Interactions by the Addition of Free Amino Acids at Millimolar Concentrations. The Journal of Physical Chemistry B 2024, 128 (29) , 7199-7207. https://doi.org/10.1021/acs.jpcb.4c01086
    2. Ruey Leng Loo, Queenie Chan, Jeremy K. Nicholson, Elaine Holmes. Balancing the Equation: A Natural History of Trimethylamine and Trimethylamine-N-oxide. Journal of Proteome Research 2022, 21 (3) , 560-589. https://doi.org/10.1021/acs.jproteome.1c00851
    3. Archita Maiti, Snehasis Daschakraborty. Can Urea and Trimethylamine-N-oxide Prevent the Pressure-Induced Phase Transition of Lipid Membrane?. The Journal of Physical Chemistry B 2022, 126 (7) , 1426-1440. https://doi.org/10.1021/acs.jpcb.1c08891
    4. Archita Maiti, Snehasis Daschakraborty. How Do Urea and Trimethylamine N-Oxide Influence the Dehydration-Induced Phase Transition of a Lipid Membrane?. The Journal of Physical Chemistry B 2021, 125 (36) , 10149-10165. https://doi.org/10.1021/acs.jpcb.1c05852
    5. Pritam Ganguly, Jakub Polák, Nico F. A. van der Vegt, Jan Heyda, Joan-Emma Shea. Protein Stability in TMAO and Mixed Urea–TMAO Solutions. The Journal of Physical Chemistry B 2020, 124 (29) , 6181-6197. https://doi.org/10.1021/acs.jpcb.0c04357
    6. Ewa Anna Oprzeska-Zingrebe, Jens Smiatek. Aqueous Mixtures of Urea and Trimethylamine-N-oxide: Evidence for Kosmotropic or Chaotropic Behavior?. The Journal of Physical Chemistry B 2019, 123 (20) , 4415-4424. https://doi.org/10.1021/acs.jpcb.9b02598
    7. Zi‐feng Lu, Chou‐Yi Hsu, Nada Khairi Younis, Mohammed Ahmed Mustafa, Elena A. Matveeva, Yassien Hussain Owaied Al‐Juboory, Mohaned Adil, Zainab H. Athab, Mustafa Nasrat Abdulraheem. Exploring the significance of microbiota metabolites in rheumatoid arthritis: uncovering their contribution from disease development to biomarker potential. APMIS 2024, 132 (6) , 382-415. https://doi.org/10.1111/apm.13401
    8. Pankaj Adhikary, Kambham Devendra Reddy, Rajib Biswas. Why does urea not alter the vibrational spectroscopic signatures of water?. Chemical Physics Impact 2024, 8 , 100609. https://doi.org/10.1016/j.chphi.2024.100609
    9. Tsung-Han Liu, Masanari Okuno. TMAO perturbs intermolecular vibrational motions of water revealed by low-frequency modes. Physical Chemistry Chemical Physics 2024, 26 (16) , 12397-12405. https://doi.org/10.1039/D4CP01025F
    10. Mohd Younus Bhat, Irfan Ahmad Mir, Mahboob Ul Hussain, Laishram Rajendrakumar Singh, Tanveer Ali Dar. Urea ameliorates trimethylamine N-oxide-Induced aggregation of intrinsically disordered α-casein protein: the other side of the urea-methylamine counteraction. Journal of Biomolecular Structure and Dynamics 2023, 41 (8) , 3659-3666. https://doi.org/10.1080/07391102.2022.2053744
    11. Mayank M. Boob, Shahar Sukenik, Martin Gruebele, Taras V. Pogorelov. TMAO: Protecting proteins from feeling the heat. Biophysical Journal 2023, 122 (7) , 1414-1422. https://doi.org/10.1016/j.bpj.2023.03.008
    12. Ashley K. Borkowski, N. Ian Campbell, Ward H. Thompson. Direct calculation of the temperature dependence of 2D-IR spectra: Urea in water. The Journal of Chemical Physics 2023, 158 (6) https://doi.org/10.1063/5.0135627
    13. Harrison Laurent, Tristan G. A. Youngs, Thomas F. Headen, Alan K. Soper, Lorna Dougan. The ability of trimethylamine N-oxide to resist pressure induced perturbations to water structure. Communications Chemistry 2022, 5 (1) https://doi.org/10.1038/s42004-022-00726-z
    14. Mazin Nasralla, Harrison Laurent, Daniel L. Baker, Michael E. Ries, Lorna Dougan. A study of the interaction between TMAO and urea in water using NMR spectroscopy. Physical Chemistry Chemical Physics 2022, 24 (35) , 21216-21222. https://doi.org/10.1039/D2CP02475F
    15. José Fabián Villa-Manríquez, Roberto Y Sato-Berrú, Jorge Castro-Ramos, Jose L Flores-Guerrero. Classification of trimethylamine-N-oxide, a cardiometabolic disease biomarker, by Raman spectroscopy and support vector machines. Journal of Physics D: Applied Physics 2022, 55 (36) , 365401. https://doi.org/10.1088/1361-6463/ac79dc
    16. Tao Li, Wei Fan, Jin Sun, Yuanqin Yu, Xiaoguo Zhou, Chuanmei Xie, Shilin Liu. The role of weak C–H···O hydrogen bond in alcohol–water mixtures. Journal of Raman Spectroscopy 2022, 53 (9) , 1551-1559. https://doi.org/10.1002/jrs.6413
    17. Zhao Yang, Paul Stemmer, Michael Petriello. Proteomics-Based Identification of Interaction Partners of the Xenobiotic Detoxification Enzyme FMO3 Reveals Involvement in Urea Cycle. Toxics 2022, 10 (2) , 60. https://doi.org/10.3390/toxics10020060
    18. Xiaoyu Shi, Wei Lu, Yichun Xue, Hang Zhou, Fei Xue, Hui He, Songlin Wang, Shuangfei Wang. Design of thermo-responsive hyperbranched nanofibre-based adsorbent with high CO2 adsorption capacity and analysis of its ultra-low temperature regeneration mechanism. Chemical Engineering Journal 2021, 424 , 130362. https://doi.org/10.1016/j.cej.2021.130362
    19. Genevieve A. Verville, Mary Hannah Byrd, Andrew Kamischke, Shelly A. Smith, David H. Magers, Nathan I. Hammer. Raman spectroscopic and quantum chemical investigation of the effects of trimethylamine N‐oxide on hydrated guanidinium and hydrogen‐bonded water networks. Journal of Raman Spectroscopy 2021, 52 (4) , 788-795. https://doi.org/10.1002/jrs.6061
    20. Olga M. Zarechnaya, Aleksei A. Anisimov, Eugenii Yu Belov, Nikolai I. Burakov, Alexander L. Kanibolotsky, Vasilii A. Mikhailov. Polycentric binding in complexes of trimethylamine- N -oxide with dihalogens. RSC Advances 2021, 11 (11) , 6131-6145. https://doi.org/10.1039/D0RA08165E
    21. D. Vijay Anand, Zhenyu Meng, Kelin Xia, Yuguang Mu. Weighted persistent homology for osmolyte molecular aggregation and hydrogen-bonding network analysis. Scientific Reports 2020, 10 (1) https://doi.org/10.1038/s41598-020-66710-6
    22. Christoph J. Sahle, Martin A. Schroer, Johannes Niskanen, Mirko Elbers, Cy M. Jeffries, Christian Sternemann. Hydration in aqueous osmolyte solutions: the case of TMAO and urea. Physical Chemistry Chemical Physics 2020, 22 (20) , 11614-11624. https://doi.org/10.1039/C9CP06785J
    23. Zhaoqian Su, Cristiano L. Dias. Individual and combined effects of urea and trimethylamine N-oxide (TMAO) on protein structures. Journal of Molecular Liquids 2019, 293 , 111443. https://doi.org/10.1016/j.molliq.2019.111443
    24. Marion M. Chan, Xiaofeng Yang, Hong Wang, Fatma Saaoud, Yu Sun, Dunne Fong. The Microbial Metabolite Trimethylamine N-Oxide Links Vascular Dysfunctions and the Autoimmune Disease Rheumatoid Arthritis. Nutrients 2019, 11 (8) , 1821. https://doi.org/10.3390/nu11081821
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    The Journal of Physical Chemistry B

    Cite this: J. Phys. Chem. B 2018, 122, 38, 8805–8811
    Click to copy citationCitation copied!
    https://doi.org/10.1021/acs.jpcb.8b04388
    Published August 30, 2018
    Copyright © 2018 American Chemical Society
    Request reuse permissions

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