Determination of the effective correlation time modulating 1H NMR relaxation processes of bound water in protein solutions

Yılmaz, Ali; Budak, Hatice; Ulak, F. Sadan

doi:10.1016/j.mri.2007.05.008

Cited by 15 publications

(15 citation statements)

References 52 publications

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“…In addition, in the presence and absence of 0.02 g albumin, the 1/T2 relaxation rate of D20 decreases linearly with increasing temperature (Fig.1). Decreasing of the 1/T1 and 1/T2 values with temperature in D20 solutions suggests that the dipole-dipole interaction mechanism is predominant [19][20][21]. In addition, the increase of 1/T1 with temperature in the D20 solutions shows that the mechanism of spin-rotation interaction is predominant.…”

Section: Resultsmentioning

confidence: 93%

“…HSA contributes to various physiological functions such as homeostasis, metabolism, protection, and also the passage and binding of endo-exogenous substrates [1,2,3]. Spin-lattice (T1) and spin-spin (T2) relaxation times of albumin solutions were studied in detail by Nuclear Magnetic Resonance Dispersion (NMRD) and Nuclear Magnetic Resonance (NMR) techniques [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21]. Several methods have been applied to explain the mechanisms of the reaction.…”

Section: Introductionmentioning

confidence: 99%

“…One of these methods is based on the derivation of albumin's rotational correlation (interest) time from the Stokes-Einstein association [8,13,16,17]. The other is based on the time of interest obtained from T1/T2 ratios [21,22]. The interest times in microseconds in the first studies are derived from nanoseconds in subsequent studies.…”

Section: Introductionmentioning

confidence: 99%

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Investigation of Temperature Dependence of D2o Solutions by 400 MHZ NMR

Balcı¹,

Ava²,

Yılmaz³

2018

mejs

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Section: Resultsmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

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Investigation of Temperature Dependence of D2o Solutions by 400 MHZ NMR

Balcı¹,

Ava²,

Yılmaz³

2018

mejs

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“…Such IR-SE mixed sequences are frequently used for T 1 measurements. [7][8][9] The D of water was determined by the pulse sequence superimposition of a pair of square-shaped gradient field pulses (the so-called motion-probing gradients) using a stimulated echo acquisition mode. The gradient pulse factor, b-value, ranged from 0 to 3339 s/mm 2 .…”

Section: Measurement Of Mr Parameters Of Emulsionsmentioning

confidence: 99%

Self-organizing Map Analysis for Understanding Comprehensive Relationships between Formulation Variables, State of Water, and the Physical Stability of Pharmaceutical Emulsions

Onuki

Hasegawa

Horita³

et al. 2015

CHEMICAL & PHARMACEUTICAL BULLETIN

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The physical stability of pharmaceutical emulsions is an important quality attribute to be considered. To obtain a better understanding of this issue, this study investigated the contribution of the state of water to the physical stability of pharmaceutical emulsions. The key technology to evaluate the state of water was magnetic resonance imaging (MRI). For sample preparation, model emulsions with different formulation variables (surfactant content, water content, and hydrophilic-lipophilic balance) were prepared. The T 1 relaxation time, diffusion coefficient, and viscosity were measured as physical properties. The physical stability of the samples was evaluated using apparent diffusion coefficient maps acquired by MRI. Data analysis of the observed data was performed using the nonlinear response surface method and Kohonen's self-organizing map (SOM). It was determined that, depending on the formulation variables, the state of water was substantially changed and it played a significant role in the physical stability. SOM analysis successfully classified the conditions of formulation variables into four distinct clusters in terms of the similarity of the physical properties of the resultant emulsions, and then clarified the characteristics of the stable emulsions. This study provided us with a comprehensive understanding of the formulation variables, physical properties, and stability concerning the preparation of the model emulsion.Key words pharmaceutical emulsion; magnetic resonance imaging; physical stability; T 1 relaxation time; diffusion coefficient Oil-in-water type emulsions are widely used for various semisolid topical dosage forms. Pharmaceutical emulsions are less greasy than ointments, they are easier to apply and can be easily washed off from the skin surface; thus, they are highly acceptable to patients. 1) For the development of pharmaceutical emulsions, physical stability is a very important quality attribute to be considered. This is because emulsions are thermodynamically unstable by nature. In general, the destabilization processes of emulsions are classified into four distinct processes: creaming, flocculation, coalescence, and Ostwald ripening.1) Coalescence and Ostwald ripening are the most serious types of destabilization, whereas creaming and flocculation are subtle destabilization processes.We have been investigating the physical stability of pharmaceutical emulsions using magnetic resonance imaging (MRI).2-4) MRI is one of the most popular molecular imaging methods; it permits the nondestructive monitoring of a sample using the principle of nuclear magnetic resonance (NMR). In addition, MRI can visualize the state of water in a sample by using magnetic resonance (MR) parameters. In a previous study, we established a new method to monitor destabilization processes of pharmaceutical emulsions.4) The key technology is the visualization of the state of water. Water in pharmaceutical emulsions can exist in various states depending on its particular location and microenvironment.2) Once cre...

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“…As a result, some water molecules associated with protein may be constrained by hydrogen bonds to the protein, and the rest may reside in a site without hydrogen bond [30]. The residence time of buried water is in the range of tens of ns [11,19,20]. In D 2 O solutions, the internal cavities or deep pockets of the protein were assumed to be occupied by D 2 O [31].…”

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confidence: 99%

NMR Proton Spin-Lattice Relaxation Mechanism in D2O Solutions of Albumin Determined at 400 MHz

2014

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T 1 values in pure D 2 O and D 2 O solutions of human serum albumin (HSA) were measured versus temperature. A formula was derived based on H-H interactions between the surface HDO and non-exchangeable protein protons. The formula was used to evaluate the average distance of the interactions (r av ). The effective correlation times were then derived by replacing the experimental data in the formula. Short correlation times obtained for the solution with low HSA (0.02 g albumin for one ml of D 2 O) decreased from 53 to 29 ps, while longer times increased from 1.19 to 2.22 ns. They are of the order of a fraction of a nanosecond for the solution with high HSA (0.08 g albumin per one ml of D 2 O). The perfect consistency between the derived theory and experimental data indicates that the high-fi eld 1/T 1 in D 2 O solutions of albumin is caused by dipolar interactions between the surface HDO and non-exchangeable protein protons. It also suggests that the effective correlation time of the surface HDO is of the order of the mean lifetime of short-lived surface water.Introduction. Albumin is a major protein of serum; it performs several physiological functions, and it is also a carrier for several kinds of substances, drugs, and contrast agents [1-3]. Understanding relaxation mechanisms in albumin solutions is still of scientifi c interest. The water-protein interaction has extensively been studied by the nuclear magnetic relaxation dispersion (NMRD) technique, and also by the use of proton NMR, 2 H, and 17 O NMRD, multi dimension NMR, and X-ray diffraction techniques . However, the dynamics of surface water-protein interactions at high fi elds have not been understood completely.NMRD profi les of H 2 O and D 2 O solutions of albumin and other proteins show two dispersions, one at low fi elds and the other at much higher fi elds [15,17]. The low-fi eld dispersion was attributed to bound water, and it yields the rotational correlation time of proteins [6,14,15,17,21]. At the beginning, the small high-fi eld dispersion was attributed to surface water on a time scale of order one ns [13,15,17]. However, the lifetime of the majority of water around albumin varies from 10 to 100 ps [9,18,[26][27][28]. Therefore, T 1 relaxation at high fi elds may be explained in terms of such short-lived surface water. In fact, some new theories related to the lifetimes or local translation mobility or diffusive motions of short-lived surface water have recently been developed to explain the T 1 mechanism at the water-protein interface [9,21,29,30]. These theories are very sophisticated, and they involve various parameters. A new approach, based on the average value of H-H distances and of correlation times, should lead to a much simpler theory. Such an approach should be a further step if the derived theory reproduces previously suggested correlation times from experimental data.The aim of this work is to asses NMR T 1 mechanism in D 2 O solutions of human serum albumin (HSA) at 400 MHz. For this purpose, the observed T 1 in D 2 O solutions ...

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Determination of the effective correlation time modulating 1H NMR relaxation processes of bound water in protein solutions

Cited by 15 publications

References 52 publications

Investigation of Temperature Dependence of D2o Solutions by 400 MHZ NMR

Investigation of Temperature Dependence of D2o Solutions by 400 MHZ NMR

Self-organizing Map Analysis for Understanding Comprehensive Relationships between Formulation Variables, State of Water, and the Physical Stability of Pharmaceutical Emulsions

NMR Proton Spin-Lattice Relaxation Mechanism in D2O Solutions of Albumin Determined at 400 MHz

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