Calculation of Dynamic Properties of Drug-Added Aqueous Solutions with T1 and T2 Relaxation Times

Öz

The development of modern spectroscopic methods has facilitated and accelerated structure analysis. The NMR method is the most popular way to perform structural analysis of compounds with very complex structures. D2O is a solvent that is frequently used in NMR analysis of both chemical molecules and many biological molecules such as drugs, proteins, and enzymes. In this paper, the study of residual water in proton drug-added protein solutions was carried out via NMR relaxation. The spin-lattice (T1) and the spin-spin relaxation (T2) times of residual water in drug-added protein solutions were studied depending on temperature by Avance Bruker 400 MHz 1H-NMR Spectrometer, and activation energies (E_a) and rotational correlation times (τ_0 and τ_c) have been determined for T1 and T2 relaxation times.

Anahtar Kelimeler

• D2O
• Proton NMR
• Relaxation times
• Activation energy
• Flurouacil

İlaç Katkılı Sulu Çözeltilerin Dinamik Özelliklerinin T1 ve T2 Rölaksasyon Zamanları ile Hesaplanması

Öz

Modern spektroskopik yöntemlerin gelişimi, yapı analizini kolaylaştırmış ve hızlandırmıştır. NMR yöntemi, çok karmaşık yapılara sahip bileşiklerin yapısal analizini gerçekleştirmenin en popüler yoludur. D2O, hem kimyasal moleküllerin hem de ilaçlar, proteinler, enzimler gibi birçok biyolojik molekülün NMR analizinde sıklıkla kullanılan bir çözücüdür. Bu çalışmada, ilaç katkılı protein çözeltilerinde residual su çalışması, proton NMR rölaksasyonu yoluyla gerçekleştirilmiştir. Avance Bruker 400 MHz 1H-NMR Spektrometresi ile ilaç katkılı protein çözeltilerinde residual suyun spin-örgü (T1) ve spin-spin rölaksasyon (T2) süreleri sıcaklığa bağlı olarak ölçülmüş, T1 ve T2 rölaksasyon süreleri için aktivasyon enerjileri (E_a) ile τ_0 ve τ_c dönme korelasyon zamanları belirlenmiştir.

Kaynakça

1. Abragam, A., The Principles of Nuclear Magnetism. Oxford: Clarendon Press, 32 ed., 599p. 1961.
2. Mathur, R., Vré, D., The NMR studies of water in biological systems, Progress in Biophysics and Molecular Biology, 35, 103-134, 1980.
3. Traficante, D.D., Relaxation. Can T2 be longer than T1?, Concepts in Magnetic Resonance, 3, 171-177, 1991.
4. Lankhorst, D., Schriever, J., Leyte, J.C., Determination of the Rotational Correlation Time of Water by Proton NMR Relaxation in H217O and Some Related Results, Berichte der Bunsengesellschaft für physikalische Chemie, 86(3), 215–221, 1982.
5. Bulla, I., Törmälä, P., Lindberg, J.J., Spin Probe Studies on the Dynamic Structure of Dimethyl Sulfoxide-Water Mixtures, Acta Chemica Scandinavica A, 29, 89–92, 1975.
6. Reich, H.J. (2017). 8.1 Relaxation in NMR Spectroscopy
7. Marchi, M., Sterpone, F., Ceccarelli, M., Water Rotational Relaxation and Diffusion in Hydrated Lysozyme, Journal of the American Chemical Society, 124(23), 6787–6791, 2002.
8. Fung, B.M., Mcgaughy, T.W., Study of Spin-Lattice and Spin-Spin Relaxation Times of 1H, 2H, and 17O in Muscle Water, Biophysical Journal, 28, 293- 304, 1979.

9. Kiihne, S., Bryant, R.G., Protein-bound water molecule counting by resolution of (1)H spin-lattice relaxation mechanisms, Biophysical Journal, 78(4), 2163-2169, 2000.
10. Kivelson, D., Rotational correlation times for small molecules in liquids, In: Dorfmüller, T., Pecora, R. Eds., Rotational Dynamics of Small and Macromolecules. Lecture Notes in Physics, 293. Springer, Berlin, Heidelberg, 1987.
11. Cope, F.W., Nuclear Magnetic Resonance Evidence using D2O for Structured Water in Muscle and Brain, Biophysical Journal, 9, 303-319, 1969.
12. Woessner, D.E., Pettegrew, J.W. eds., Relaxation Theory with Applications to Biological Studies. In: NMR: Principles and Applications to Biomedical Research, Springer, New York, 618p. 1990.
13. Solomon, I., Relaxation Processes in a System of Two Spins, Physical Review, 99(2), 559-565, 1955.
14. Bloembergen, N., Purcell, E.M., Pound, R.V., Relaxation Effects in Nuclear Magnetic Resonance Absorption, Physical Review, 73(7), 679-712, 1948.
15. Güven, M., Köylü, M.Z., Dynamic Investigation of β-Hydroxy Amide Derivatives by 400 MHz 1H-NMR, International Journal of Science and Research, 7(10), 1130-1133, 2018.
16. Bryant, R.G., Korb, J.P., Nuclear magnetic resonance and spin relaxation in biological systems, Magnetic Resonance Imaging, 23(2), 167-173, 2005.
17. Van-Quynh, A., Willson, S., Bryant R.G., Protein Reorientation and Bound Water Molecules Measured by 1H Magnetic Spin-Lattice Relaxation, Biophysical Journal, 84(1), 558-563, 2003.
18. Halle, B., Protein hydration dynamics in solution: a critical survey, Philosophical Transactions of the Royal Society B, 359 (81448), 1207-1224, 2004.
19. Venu, K., Denisov, V.P., Halle, B., Water 1H Magnetic Relaxation Dispersion in Protein Solutions. A Quantitative Assessment of Internal Hydration, Proton Exchange, and Cross-Relaxation, Journal of the American Chemical Society, 119(13), 3122–3134, 1997.
20. Tadimalla, S., Momot, K.I., Effect of partial H2O-D2O replacement on the anisotropy of transverse proton spin relaxation in bovine articular cartilage, PLoS One, 9(12), 2014.
21. Gultekin, D.H., Gore, J.C., Temperature dependence of nuclear magnetization and relaxation, Journal of Magnetic Resonance, 172(1), 133- 141, 2005.
22. Singer, P.M., Asthagiri, D., Chapman, W.G., Hirasaki, G.J., Molecular dynamics simulations of NMR relaxation and diffusion of bulk hydrocarbons and water, Journal of Magnetic Resonance, 277, 15-24, 2017.
23. Zhang, L., Bouguet-Bonnet, S., Buck, M., Combining NMR and molecular dynamics studies for insights into the allostery of small GTPase-protein interactions, Methods in Molecular Biology, 796, 235-59, 2012.
24. Korb, J.P., Bryant, R.G., Magnetic Field Dependence of Proton Spin-Lattice Relaxation Times, Magnetic Resonance in Medicine, 48, 21–26, 2002.
25. Noskov, S.Y., Kiselev, M., Kolker, A.M., Role of bound water in protein-ligand association processes, Biophysics, 55(1), 29-34, 2010.
26. Rezus, Y.L.A., Bakker, H.J., On the orientational relaxation of HDO in liquid water, The Journal of Chemical Physics, 123, 114502, 2005.
27. Lawrence, C.P., Skinner, J.L., Vibrational spectroscopy of HOD in liquid D2O. III. Spectral diffusion, and hydrogen-bonding and rotational Dynamics, The Journal of Chemical Physics, 118, 264, 2003.
28. Duplan, J.C., Mahi, L., Brunet, J.L., NMR determination of the equilibrium constant for the liquid H2O–D2O mixture, Chemical Physics Letters, 413, 400-403, 2005.
29. Thuduppathy, G.R., Hill, R.B., Applications of NMR spin relaxation methods for measuring biological motions, Methods in Enzymology, 384, 243-64, 2004.
30. Gallot, G., Lascoux, N., Gale, G.M., Leicknam, J-Cl., Bratos, S., Pommeret, S., Non-monotonic decay of transient infrared absorption in dilute HDO/D2O solutions, Chemical Physics Letters, 341, 535-539, 2001.
31. Korunur, S., Zengin, B., Yilmaz, A., Investigation of relaxation times in 5-fluorouracil and human serum albumin mixtures, Turkish Journal of Biochemistry, 44(4), 524-529, 2019.
32. Reuhl, M., Vogel, M., Temperature-dependent dynamics at protein-solvent interfaces, The Journal of Chemical Physics, 157(7), 074705, 2022.
33. Halle, B., Denisov, V.P., A new view of water dynamics in immobilized proteins, Biophysical Journal, 69(1), 242-9, 1995.
34. Goddard, Y.A., Korb, J.P., Bryant R.G., Water molecule contributions to proton spin-lattice relaxation in rotationally immobilized proteins, Journal of Magnetic Resonance, 199(1), 68-74, 2009.
35. Charlier, C., Cousin, S.F., Ferrage, F., Protein dynamics from nuclear magnetic relaxation, Chemical Society Reviews, Royal Society of Chemistry, 45(9), 2410-2422, 2016.
36. Mallamace, F., Corsaro, C., Mallamace, D., Baglioni, P., Stanley, H.E., Chen S.H., A possible role of water in the protein folding process, The Journal of Physical Chemistry B, 115(48), 14280-94, 2011.
37. Köylü, M.Z., Temperature Dependences of T1 and T2 of Residual Water in D2O Determined at 400 MHz 1H-NMR, International Journal of Science and Research, 7(10), 40-43, 2018.