LIGHT SCATTERING IN RESEARCH AND QUALITY CONTROL OF DEUTERIUM DEPLETED WATER FOR PHARMACEUTICAL APPLICATION
Objective: Development of a methodology for measuring the deuterium content in water for pharmaceutical purposes by laser light scattering on the basis of ideas about the cluster structure of water.
Methods: Samples of industrially manufactured drinking water from different manufacturers with varying deuterium content from 10 ppm to 115 ppm. For the titration of laboratory samples of deuterium depleted water in increments of 5 ppm the following reagents were used: Water, deuterium-depleted (≤1 ppm (D2O, ALDRICH); Deuterium oxide/ Heavy water/Water-d2 (99.9 atom % D, ALDRICH; water Mili-Q (specific resistance 18.2 MΩ·cm at 25оС, ТОС ≤ 5 ppb, Merck Millipore). The determination of deuterium content in samples of industrially manufactured water and water obtained in a laboratorial manner was carried out by the method of low-angle laser light scattering (LALLS) at the Mastersizer (Malvern Instruments) analyser and using a working measuring tool – laser dispersion meter/ MDL («Cluster-1», Russia/Ukraine). The statistical methods – packages OriginPro®9.
Results: It was found that the content of isotopologues in water leads to changes in the morphology of giant heterogeneous water clusters (GHC). The results of low-angle laser light scattering in the water samples under investigation showed the dependence of the GHC "dispersability" expressed in the differentiation of the laser obscuration values (I ‒I0), the volume concentration, w,% and the curves of the volume size distribution function of the variations of the isotopic composition of water. The results of the LALLS-method correlate with the calculations made by us using a computer model and reliably describe the analytical characteristics of the samples for the comparative research using physical and chemical descriptors.
Conclusion: When identifying deuterium depleted water, it should be taken into account not only the indicators that determine its pharmacopoeial quality, but also the D/H ratio, because even small changes in the natural isotopic composition of water lead to significant biological effects. Our proposed approach using physical and mathematical model makes possible the exact calculation of individual signs of deuterium depleted water as the pharmaceutical object of study.
2. Guideline on the quality of water for pharmaceutical use. European Medicines Agency: London; United Kingdom; 2018. 10 p.
3. Xiao W, Wen X, Wang W, Xiao Q, Xu J, Cao C, Xu J, Hu C, Shen J, Liu, Lee X. Spatial distribution and temporal variability of stable water isotopes in a large and shallow lake. Isotopes in Environmental and Health Studies 2016; 2:443-454.
4. Gabriel JB, James RE, Lesley AC, Erik, Thure E. Stable isotope ratios of tap water in the contiguous United States. Water resources research 2007; 43: 45-65.
5. Schoenemann SW, Schauer AJ, Steig EJ. Measurement of SLAP and GISP ?17O and proposed VSMOW-SLAP normalization for ?17O and 17O(excess). Rapid Commun Mass Spectrom 2013; 27(5):582-90.
6. Gehre M, Höfling R, Kowski P. Methodical studies for d/h-isotope analysis - a new technique for the direct coupling of sample preparation to an irms. Isotopes Environ Health Stud 1996; 32(4):335-40.
7. Barkan E, Luz B. High precision measurements of 17O/16O and 18O/16O ratios in H2O.Rapid Commun Mass Spectrom 2005; 19(24):3737-42.
8. Mladin C, Popescu AL, Stefanescu I, Oubraham A. Deuterium Depleted Water-New Studies About Isotopic Distillation Obtaining Process. Asian Journal of Chemistry 2013; 25 (14): 7976-7978.
9. Rehakova R, Klimentova J, Cebova M, Barta A, Matuskova Z, Labas P, Pechanova O. Effect of deuterium-depleted water on selected cardiometabolic parameters in fructose-treated rats. Physiol Res. 2016:S401-S407.
10. Christopher MH, Pollegioni L, Ghisla S. pH and kinetic isotope effects in d?amino acid oxidase catalysis. European Journal of Biochemistry 2001:268 (21): 5504-20.
11. Gorokhov VV, Knox PP, Korvatovsky BN, Paschenko VZ, Zakharova NI, Rubin AB. Effect of deuteration and cryosolvents on the energy transduction in primary processes of photosynthesis. Membr Cell Biol 1998; 12(5):593-608.
12. Makhatadze GI, Clore GM, Gronenborn AM. Solvent isotope effect and protein stability. Nat Struct Biol. 1995; 2(10):852-5.
13. Mei M. Whittaker, David P. Ballou, James W. Whittaker Kinetic Isotope Effects as Probes of the Mechanism of Galactose Oxidase. Biochemistry 1998; 37 (23), 8426-8436.
14. Somlyai G, Jancsbb G, Jhklib G, Vass K, Barna B, Lakicsd V, Gahld T. Naturally occurring deuterium is essential for the normal growth rate of cells. European Biochemical Societies 1993; 317 (1): 2- 14.
15. Vorozhtsova SV, Abrosimova AN, Kulikova EI, Dorozhkina OV, Kovalenko MA, Kriuchkova DM, Severiukhin IuS, Gaevski? VN, Siniak IuE, Ivanov AA. Modification of the cytogenetic effects of irradiation by water with the reduced content of deuterium and heavy isotopes of oxygen. Radiats Biol Radioecol 2014; 54(1):21-6.
16. Somlyai G., Laskay G., Berkényi T. et al. The biological effects of deuterium-depleted water, a possible new tool in cancer therapy. Journal of Oncology 2001; 30: 91-94.
17. Somlyai G. The biological effect of deuterium-depleted water. A possible new tool in cancer therapy. Anticancer Research Intern. J. 2002: 21(3): 23-33
18. Somlyai G., Molnár M, Laskay G, Szabó M, Berkényi T, Guller I, Kovács A. Biological significance of naturally occurring deuterium: the antitumor effect of deuterium depletion. Orv Hetil. 2010:151(36):1455-60
19. Gyöngyi Z, Budán F, Szabó I, Ember I, Kiss I, Krempels K, Somlyai I, Somlyai G. Deuterium depleted water effects on survival of lung cancer patients and expression of Kras, Bcl2, and Myc genes in mouse lung. Nutr Cancer. 2013 65(2):240-6.
20. Stom DI, Ponomareva AK, Vyatchina OF. Deuterium depletion from tissue culture to human clinical studies. In: 2nd International Congress on Deuterium Depletion 2006: 12(4): 20 -21.
21. Török G, Cskí M, Pinté, A. Influense of water with varying content of deuterium on red Californian hybride (Eusenia fetida Andrei Bouche). Bull. RAS 2000: 6(52): 167–169.
22. Thomson JF. Effects of different deuterium concentrations of the media on the bacterial growth and mutagenesis. Egészségtudomány/Health Science 1960: 44: 331-338.
23. Tsukamoto H. Physiological effects of D2O in mammals. Deuterium isotope effects in chemistry and biology. Annals of the New York Academy of Sciences 2009: 84: 736-744.
24. Rehakova R, Klimentova J, Cebova M, Barta A, Matuskova Z, Labas P, Pechanova O. Age-associated increase in lifespan of navïe CD4 T cells contributes to T-cell homeostasis but facilitates development of functional defects. Proc. Natl. Acad. Sci. USA 2009: 106(43): 18333–18338.
25. Rehakova R, Klimentova J, Cebova M, Barta A, Matuskova Z, Labas P, Pechanova O. Effect of deuterium-depleted water on selected cardiometabolic parameters in fructose-treated rats. Physiol. Res. 2016: S401-S407.
26. Nelson D, William F. Trager the use of deuterium isotope effects to probe the active site properties, mechanism of cytochrome p450-catalyzed reactions, and mechanisms of metabolically dependent toxicity Sidney. Drug metabolism and disposition 2003: 31 (12): 1481–1498.
27. Ding Z, Hou Y, Wang S, Sun T, Ma M, Guan H, Li W. Synthesis of deuterium-enriched and fluorine-substitutedplinabulin derivatives and evaluation of their antitumor activities Mol Divers. 2017: 21(3):577-583.
28. Kaur S, Gupta M. Deuteration as a Tool for Optimization of Metabolic Stability and Toxicity of Drugs. Glob J Pharmaceu Sci 2017: 1(4): 001 – 0011.
29. Uspenskaya EV, Anfimova EV, Syroeshkin AV, Pleteneva TV. Kinetics of pharmaceutical substance solubility in water with different hydrogen isotopes content. Indian J Pharm Sci 2018; 80:318-24.
30. Syroeshkin AV, Pleteneva TV, Uspenskaya EV, Levitskaya OV, Tribot-laspiere MA, Zlatsky IA, et al. Polarimetric research of pharmaceutical substances in aqueous solutions with different water isotopologues ratio. Int J App Pharm 2018;10:243-8.
31. Gyöngyi Z, Somlyai G. Deuterium depletion can decrease the expression of C-myc Ha-ras and p53 gene in carcinogen-treated mice. In Vivo. 2000 May-Jun;14(3):437-9.
32. Voronina ?V, Fedorchenko ??. Measuring the protium concentration in highly concentrated heavy water by IR spectrometry. Progress of Criogenics and Isotopes Separation. Rm Valcea 2006:17(18): 24-30.
33. Tachikawa M, Shiga M. Geometrical H/D Isotope Effect on Hydrogen Bonds in Charged Water Clusters. Am Chem Soc. 2005: 4 (34): 1908-1909.
34. Scott B, Penny K. A Decision Support System for Rectification Action Planning in the Sydney Drinking Water Catchments. Engineers Australia; Causal Productions 2008:2261-2272.
35. Syroeshkin AV, Popov PI, Grebennikova TV. Laser diffraction for standardization of heteroge-neous pharmaceutical preparations. J Pharm Biomed Anal 2005;37:927-30.
36. Hung J, Barton J. Dear, Carl A. Karouta, Amjad A. Chowdhury, P. Douglas Godfrin, Jonathan A. Bollinger, et al. Johnston Protein–Protein Interactions of Highly Concentrated Monoclonal Antibody Solutions via Static Light Scattering and Influence on the Viscosity Jessica The Journal of Physical Chemistry 2019:123 (4), 739-55.
37. Uspenskaya EV, Syroeshkin AV, Smirnov AN. The structure of water and laser rapid methods for determining authenticity. Farmatsiya 2007; (5): 21–23 (in Russian).
38. Dengsheng Z, Lu. A. Guojun Comparative Study on Shape Retrieval Using Fourier Descriptors with Different Shape Signatures. Journal of Visual Communication and Image Representation 2003: 14 (1): P. 41-60.
39. Syroeshkin AV, Stepanova NA, Popov PI, et al. Prognostication of toxicity of a group of chemical compounds comprising anti-tuberculosis medicines by the quantitative structure-activity correlation method. Forensic Med Exam 2009; (4): 210–17
40. Goncharuk VV, Lapshin VB, Burdeinaya TN, Pleteneva TV, Chernopyatko AS, Atamanenko ID, et al. Physicochemical Properties and Biological Activity of the Water Depleted of Heavy Isotopes Journal of Water Chemistry and Technology 2011: 33(1): 8–13.
41. Goncharuk VV, Pleteneva TV, Grebennikova TV, Syroeshkin AV, Uspenskaya EV, Antipova NV, et al. Determination of Biological Activity of Water Having a Different Isotope Ratio of Protium and Deuterium. Journal of Water Chemistry and Technology 2018;40:27-34
42. Yakhno T, Yakhno VA. Study of the Structural Organization of Water and Aqueous Solutions by Means of Optical Microscopy. Crystals. 2019; 9(1), 52.
43. Abascal J L F, Bresme F. The influence of concentration and ionic strength on the cluster structure of highly charged electrolyte solutions. Molecular physics. 1994; 81 (1): 143-156.
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