Spectroscopic Studies on the Thermodynamics of L-Cysteine Capped CdSe/CdS Quantum Dots��BSA Interactions

CdSe/CdS quantum dots (QDs) capped with L-cysteine can provide an effective platform for the interactions with bovine serum albumin (BSA). In this study, absorption and fluorescence (FL) spectroscopy were used to study the binding reactions of QDs with BSA, respectively. The binding constant (??10⁴ M^-1) from FL quenching method matches well with that determined from the absorption spectral changes. The modified Stern-Volmer quenching constant (5.23?×?10⁴, 5.22?×?10⁴, and 4.90?×?10⁴ M^-1) and the binding sites (??1) at different temperatures (304 K, 309 K, and 314 K) and corresponding thermodynamic parameters were calculated (?G?<?0, ?H?<?0, and ?S?<?0). The results show the quenching constant is inversely correlated with temperature. It indicates the quenching mechanism is the static quenching in nature rather than dynamic quenching. The negative values of free energy (?G?<?0) suggest that the binding process is spontaneous, ?H?<?0 and ?S?<?0 suggest that the binding of QDs to BSA is enthalpy-driven. The enthalpy and entropy changes for the formation of ground state complex depend on the capping agent of QDs and the protein types. Furthermore, the reaction forces were discussed between QDs and BSA, and the results show hydrogen bonds and van der Waals interactions play a major role in the binding reaction.     

Interaction Between Isoquercitrin and Bovine Serum Albumin by a Multispectroscopic Method

ABSTRACT

The interaction of isoquercitrin and bovine serum albumin (BSA) was investigated by means of fluorescence spectroscopy (FS), resonance light scattering spectroscopy (RLS), and ultraviolet spectroscopy (UV). The apparent binding constants (K _a) between isoquercitrin and BSA were 5.37 × 10⁵ L mol^?1 (293.15 K) and 2.34 × 10⁵ L mol^?1 (303.15 K), and the binding site values (n) were 1.18 ± 0.03. According to the Förster theory of non-radiation energy transfer, the binding distances (r) between isoquercitrin and BSA were 1.94 and 1.95 nm at 293.15 K and 303.15 K, respectively. The experimental results showed that the isoquercitrin could be inserted into the BSA, quenching the inner fluorescence by forming the isoquercitrin–BSA complex. The addition of increasing isoquercitrin to BSA solution leads to the gradual enhancement in RLS intensity, exhibiting the formation of the aggregate in solution. It was found that both static quenching and non-radiation energy transfer were the main reasons for the fluorescence quenching. The entropy change and enthalpy change were negative, which indicated that the interaction of isoquercitrin and BSA was driven mainly by van der Waals interactions and hydrogen bonds. The process of binding was a spontaneous process in which Gibbs free energy change was negative.     

Nitroaniline Isomers Interaction with Bovine Serum Albumin and Toxicological Implications

The interactions of 2-nitroaniline (2-NA), 3-nitroaniline (3-NA) and 4-nitroaniline (4-NA) with bovine serum albumin (BSA) have been investigated by means of fluorescence spectrometry, synchronous fluorescence spectrometry and UV absorption spectrometry under the simulative physiological conditions. Association constants (K _A ) were estimated by the remarkable static quenching effect of 2-NA, 3-NA and 4-NA to the intrinsic fluorescence of BSA, and thermodynamic parameters such as enthalpy change (ΔH) and entropy change (ΔS) were calculated according to van’t Hoff equation. The results show that hydrophobic force plays a main role in the interaction of nitroanilines to BSA, nitroanilines have high affinity to BSA and the affinity order is as follows: 4-NA?>?2-NA?>?3-NA. On the basis of this study, it is found that percents of the binding of nitroanilines to BSA are almost no relative to the concentrations of nitroanilines, and correlation between K _A and logK _ow is disclosed. In the meantime, relationships between the combination of nitroanilines with BSA and toxicological implications were also discussed. In addition, synchronous fluorescence method was used to study the interaction mechanisms between nitroanilines and BSA, and energy transfer distances from BSA to nitroanilines were estimated based on the Förster’s non-radiation energy transfer theory. The results suggest that the binding site for nitroanilines on BSA is close to the sub-domain IIA where Trp 214 is located.     

Synthesis,DNA/HSA Interaction Spectroscopic Studies and In Vitro Cytotoxicity of a New Mixed Ligand Cu(II) Complex

A new mixed ligand copper(II)-dipeptide complex with 2-(2′-pyridyl)benzothiazole (pbt), [Cu(Gly-L-leu)(pbt)(H₂O)]·ClO₄ (Gly-L-leu = Glycyl-L-leucine anion) was synthesized and characterized by various physico-chemical means. The DNA binding and cleavage properties of the complex investigated by viscosity, agarose gel electrophoresis and multi-spectroscopic techniques (UV, circular dichroism (CD) and fluorescence) showed that the complex was bound to CT-DNA through intercalation mode with moderate binding constant (K _b = 3.132 × 10⁴ M^?1), and cleaved pBR322 DNA efficiently (~ 5 μM) in the presence of Vc, probably via an oxidative mechanism induced by ?OH. Additionally, the interaction of the complex with human serum albumin (HSA) was explored by UV-visible, CD, fluorescence, synchronous fluorescence and 3D fluorescence spectroscopy. The complex exhibits desired affinity to HSA through hydrophobic interaction. Moreover, the cytotoxicity of the complex against three human carcinoma cell lines (HeLa, HepG2 and A549) was evaluated by MTT assay, which showed that the complex had effective cytotoxicity and higher inhibition toward A549 cell lines with IC₅₀ of 38.0 ± 3.2 μM.     

Studies on kinetics and thermodynamics of ion adsorption reactions by applications of short-lived radioactive tracer isotopes

The short-lived radiotracer isotopes were applied to study the kinetics and thermodynamic feasibility of iodide as well as bromide ion adsorption reactions using industrial-grade resin materials. Free energy of activation (ΔG ^?) and energy of activation (E _a) were calculated by using Arrhenius equation, enthalpy of activation (ΔH ^?), and entropy of activation (ΔS ^?) calculated by using the Eyring-Polanyi equation. These parameters were used to predict the thermodynamic feasibility of the two ion adsorption reactions performed by using Dowex SBR LC and Indion-810 resins. It was observed that during iodide ion adsorption reactions, the values of energy of activation (?18.79 kJ mol^?1), enthalpy of activation (?21.37 kJ mol^?1), free energy of activation (58.13 kJ mol^?1), and entropy of activation (?0.26 kJ K^?1 mol^?1) calculated for Indion-810 resins were lower than the respective values of ?4.28 kJ mol^?1, ?6.87 kJ mol^?1, 64.97 kJ mol^?1, and ?0.23 kJ K^?1 mol^?1 calculated for Dowex SBR LC under similar experimental conditions. Identical trends were observed for the two resins during bromide ion adsorption reactions. The low values of different thermodynamic parameters obtained for Indion-810 resins during both the ion adsorption reactions indicate that the reactions are thermodynamically more feasible using Indion-810 resins as compared to Dowex SBR LC resins. It is expected here that the present nondestructive technique can be extended further for different ions in the solution in order to predict the thermodynamic feasibility of different ion adsorption reactions for the range of resins which are widely used for treatment of industrial waste water effluent.     

Interactions between 4-(2-dimethylaminoethyloxy)-N-octadecyl-1,8-naphthalimide and serum albumins: Investigation by spectroscopic approach

A novel 4-(2-dimethylaminoethyloxy)-N-octadecyl-1,8-naphthalimide (DON) has been synthesized as a spectrofluorimetric probe for the determination of proteins. Photophysics of DON in different solvents has been delineated in this paper. Progressive redshift with polarity of solvents in emission and absorption spectra hints at intramolecular charge transfer. The interactions of DON with serum albumins (i.e., human serum albumin (HSA) and bovine serum albumin (BSA)) were studied by fluorescence and absorption spectroscopy. Fluorescence data revealed that the quenching of HSA/BSA by DON were static quenching and the DON–HSA/BSA complexes were formed. The binding constant (K_b) for HSA and was found to be 8.44×10^?4 and 60.26×10^?4 M^?1 and the number of binding sites (n) were 1.00 and 1.40, respectively. The thermodynamic parameters, ΔH and ΔS, for the DON–HSA system was calculated to be ?14.83 kJ mol^?1 and 23.61 J mol^?1 K^?1, indicating the hydrogen bonds and hydrophobic interactions were the dominant intermolecular force. ΔH and ΔS for the binding of DON with BSA was ?60.08 kJ mol^?1 and ?90.7441 mol^?1 K^?1, suggesting the hydrogen bonds and van der Waals force played the main role in the interaction. The results of displacement experiments showed that DON bound HSA/BSA occurred at the Trp-214 proximity, located in subdomain IIA of the serum albumin structure (the warfarin binding pocket). The effect of DON on the conformation of HSA was also analyzed by synchronous and three-dimensional fluorescence spectra. The fluorescence of DON could be quenched by HSA, based on which, a fluorometric method for the determination of microamount protein using DON in the medium of HCl?Tris buffer solution (pH=7.4) was developed. The linear range of the calibration curves was 0.1–10.0 μM for HSA, 0.1–11.2 μM for BSA and 0.2–9.7 μM for egg albumin (EA). The detection limit (3σ) for HSA was 1.12×10^?10 M, for BSA it was 0.92×10^?10 M and for EA it was 4.33×10^?10 M. The effect of metal cations on the fluorescence spectra of DON in ethanol was also investigated. The method has been applied to detect the total proteins in human serum samples and the results were in good agreement with those reported by the hospital.     

Solar system constraints on asymptotically flat IR modified Hořava gravity through light deflection

In this paper, we study the motion of photons around a Kehagias–Sfetsos (KS) black hole and obtain constraints on IR modified Ho?ava gravity without cosmological constant (~Λ _W ). An analytic formula for the light deflection angle is obtained. For a propagating photon, the deflection angle δφ increases with large values of the Ho?ava gravity parameter ω. Under the UV limit \({\omega \longrightarrow \infty}\), deflection angle reduces to the result of usual Schwarzschild case, 4GM/R. It is also found that with increasing scale of astronomical observation system the Ho?ava–Lifshitz gravity should satisfy |ω M ²| > 1.1725 × 10^?16 with 12% precision for Earth system, |ω M ²| > 8.27649 × 10^?17 with 17% precision for Jupiter system and |ω M ²| > 8.27650 × 10^?15 with 0.17% precision for solar system.     

Interaction of Sulfadiazine with Model Water Soluble Proteins: A Combined Fluorescence Spectroscopic and Molecular Modeling Approach

The binding behavior of antibacterial drug sulfadiazine (SDZ) with water soluble globular proteins like bovine as well as human serum albumin (BSA and HSA, respectively) and lysozyme (LYS) was monitored by fluorescence titration and molecular docking calculations. The experimental data reveal that the quenching of the intrinsic protein fluorescence in presence of SDZ is due to the strong interaction in the drug binding site of the respective proteins. The Stern-Volmer plot shows positive deviation at higher quencher concentration for all the proteins and was explained in terms of a sphere of action model. The calculated fluorophore-quencher distances vary within 4?~?11 Å in different cases. Fluorescence experiments at different temperature indicate thermodynamically favorable binding of SDZ with the proteins with apparently strong association constant (~10⁴–10⁵ M^?1) and negative free energy of interaction within the range of ?26.0?~??36.8 kJ mol^?1. The experimental findings are in good agreement with the respective parameters obtained from best energy ranked molecular docking calculation results of SDZ with all the three proteins.     

Fluorescence Quenching Study on the Interaction between Quercetin and Lipoxygenase

The interaction between quercetin and lipoxygenase was investigated by fluorescence spectroscopy. The analysis of the emission quenching at different temperatures revealed that the quenching mechanism correspond to a static process and, as consequence, a complex quercetin-lipoxygenase is formed. The thermodynamic parameters ΔG, ΔH and ΔS were calculated to be?32.57 kJmol^?1,?3.21 kJmol^?1 and 87.14 Jmol^?1K^?1 respectively, which suggest that hydrophobic forces plays a major role in the stabilization of the complex quercetin-lipoxygenase. The distance, r, between donor (lipoxygenase) and acceptor (quercetin) was calculated to be 3.84 nm based on Förster’s non-radiative energy transfer theory. The results obtained from the evaluation of three dimensional florescence spectra suggest a conformational modification of the protein in the region of the coupling with quercetin.     

Green electrolytes based on dextran-chitosan blend and the effect of NH<Subscript>4</Subscript>SCN as proton provider on the electrical response studies

Dextran-chitosan blend added with ammonium thiocyanate (NH₄SCN)-based solid polymer electrolytes are prepared by solution cast method. The interaction between the components of the electrolyte is verified by Fourier transform infrared (FTIR) analysis. The blend of 40 wt% dextran-60 wt% chitosan is found to be the most amorphous ratio. The room temperature conductivity of undoped 40 wt% dextran-60 wt% chitosan blend film is identified to be (3.84?±?0.97)?×?10^?10 S cm^?1. The inclusion of 40 wt.% NH₄SCN to the polymer blend has optimized the room temperature conductivity up (1.28?±?0.43)?×?10^?4 S cm^?1. Result from X-ray diffraction (XRD) and differential scanning calorimetry (DSC) analysis shows that the electrolyte with the highest conductivity value has the lowest degree of crystallinity (χ _c) and the glass transition temperature (T _g), respectively. Temperature-dependence of conductivity follows Arrhenius theory. From transport analysis, the conductivity is noticed to be influenced by the mobility (μ) and number density (n) of ions. Conductivity trend is further verified by field emission scanning electron microscopy (FESEM) and dielectric results.     

Ion dynamics in methylcellulose–LiBOB solid polymer electrolytes

A polymer electrolyte system comprising methylcellulose (MC) as the host polymer and lithium bis(oxalato) borate (LiBOB) as the lithium ion source has been prepared via the solution cast technique. The electrolyte with the highest conductivity of 2.79 μS cm^?1 has a composition of 75 wt% MC–25 wt% LiBOB. The mobile ion concentration (n) in this sample was estimated to be 5.70?×?10²⁰ cm^?3. A good correlation between ionic conductivity, dielectric constant, and free ion concentration has been observed. The ratio of mobile ion number density (n) at a particular temperature to the concentration n ₀ of free ions at T?=?∞ (n/n ₀) and the power law exponents (s) exhibit opposite trends when varied with salt concentration.     

Structural,electrical, and transport number studies of AgI-doped silver borotellurite fast ion conducting glass system

Silver ion conducting glass system composed of xAgI–(100???x)[0.444 Ag₂SO₄–0.555 (0.4TeO₂–0.6B₂O₃)] has been prepared by melt quenching method for x?=?0 to 80 in step of 10. XRD, DSC, FTIR, and SEM were carried out to understand some structural properties of prepared samples. XRD and DSC studies of the samples with x?≤?60 show predominantly glassy nature. Electrical parameters and activation energies of all the samples were evaluated by complex impedance analysis and Arrhenius plots of DC conductivity, respectively. Carrier concentration, mobility, inter-ionic distance, and ionic conductivity of samples were measured and discussed. It is observed that the conductivity varies with increasing the temperature and composition. The highest conductivity (1.8?×?10^?1 S cm^?1) and ionic current (8.33 μA) is observed for =?50 sample at room temperature; hence, it can be used as best electrolyte material for solid-state battery application.     

A Fluorescence Study of New Angular Polycyclic Blue Light-Emitting pyrazolo[3,4-<Emphasis Type="Italic">h</Emphasis>][1,6]naphthyridine and their Interaction with Bovine Serum Albumin (BSA)

The blue light-emitting pyrazolo[3,4-h][1,6]naphthyridines has been synthesized by Friedländer condensation of 4-amino-3-(4-phenyl)-1-phenyl-1H-pyrazolo[3,4-b]pyridine-5-carbaldehyde (o-aminoaldehyde) 1 with different cyclic ketones and 1,3-diketones. The synthesized angular polycyclic naphthyridine derivatives were studied for Semi-empirical, thermal, UV–vis and fluorescence spectroscopic properties on binding with bovin serum albumin (BSA). These fluorescence properties together with the neutral, hydrophobic nature of these compounds make these fluorophores good fluorescence probe for studying the micropolarity of proteins like BSA and in general the ligand-protein interactions. All of them displays bright absorption at 394 nm &; emission in visible region (491 nm). Quantum yields of all synthesized compounds were calculated.     

Studies on structural and electrical properties of Mg<Subscript>0. 5+y</Subscript> (Zr<Subscript>2-y</Subscript>Fe<Subscript>y</Subscript>) <Subscript>2</Subscript> (PO<Subscript>4</Subscript>) <Subscript>3</Subscript> ceramic electrolytes

The sample of Mg_{0. 5+y} (Zr_1-y Fe_y) ₂ (PO₄) ₃ (0.0 ≤y ≤0.5) was synthesized using the sol-gel method. The structures of the samples were investigated using X-ray diffraction and Fourier transform infrared spectroscopy measurement. XRD studies showed that samples had a monoclinic structure which was iso-structured with the parent compound, Mg_0.5Zr (PO₄) ₃. The complex impedance spectroscopy was carried out in the frequency range 1–6 MHz and temperature range 303 to 773 K to study the electrical properties of the electrolytes. The substitutions of Fe³⁺ with Zr⁴⁺ in the Mg_0.5Zr (PO₄) ₃ structure was introduced as an extrainterstitial Mg²⁺ ion in the modified structured. The compound of Mg_0.5+y (Zr_1-y Fe_y)₂(PO₄)₃ with y?=?0.4 gives a maximum conductivity value of 1.25?×?10^?5 S cm^?1 at room temperature and 7.18?×?10^?5 S cm^?1 at 773 K. Charge carrier concentration, mobile ion concentration, and ion hopping rate are calculated by fitting the conductance spectra to power law variation, σ _ac (ω)?=?σ _o ? +?Aω ^α . The charge carrier concentration and mobile ion concentration increases with increase of Fe³⁺ inclusion. This implies the increase in conductivity of the compounds was due to extra interstitial Mg²⁺ ions.     

Fluorescence Study on the Interaction of Bovine Serum Albumin with P-Aminoazobenzene

In this paper, the interaction between p-aminoazobenzene (PAAB) and BSA was investigated mainly by fluorescence quenching spectra, circular dichroism (CD) and three-dimensional fluorescence spectra under simulative physiological conditions. It was proved that the fluorescence quenching of BSA by PAAB was mainly a result of the formation of a PAAB-BSA complex. The modified Stern-Volmer quenching constant K _a and the corresponding thermodynamic parameters ΔH, ΔG and ΔS at different temperatures were calculated. The results indicated that van der Waals interactions and hydrogen bonds were the predominant intermolecular forces in stabilizing the complex. The distance r?=?4.33 nm between the donor (BSA) and acceptor (PAAB) was obtained according to Förster’s non-radioactive energy transfer theory. The synchronous fluorescence, CD and three-dimensional fluorescence spectral results showed that the hydrophobicity of amino acid residues increased and the losing of α-helix content (from 63.57 to 51.83%) in the presence of PAAB. These revealed that the microenvironment and conformation of BSA were changed in the binding reaction.     

Lithium diffusion in Li<Subscript>3</Subscript>V<Subscript>2</Subscript>(PO<Subscript>4</Subscript>)<Subscript>3</Subscript>-based electrodes: a joint analysis of electrochemical impedance,cyclic voltammetry,pulse chronoamperometry,and chronopotentiometry data

In order to establish the mechanism and to determine the parameters of lithium transport in electrodes based on lithium-vanadium phosphate (Li₃V₂(PO₄)₃), the kinetic model was designed and experimentally tested for joint analysis of electrochemical impedance (EIS), cyclic voltammetry (CV), pulse chronoamperometry (PITT), and chronopotentiometry (GITT) data. It comprises the stages of sequential lithium-ion transfer in the surface layer and the bulk of electrode material’s particles, including accumulation of lithium in the bulk. Transfer processes at both sites are of diffusion nature and differ significantly, both by temporal (characteristic time, τ) and kinetic (diffusion coefficient, D) constants. PITT data analysis provided the following D values for the predominantly lithiated and delithiated forms of the intercalation material: 10^?9 and 3 × 10^?10 cm² s^?1, respectively, for transfer in the bulk and 10^?12 cm² s^?1 for transfer in the thin surface layer of material’s particles. D values extracted from GITT data are in consistency with those obtained from PITT: 3.5–5.8 × 10^?10 and 0.9–5 × 10^?10 cm² s^?1 (for the current and currentless mode, respectively). The D values obtained from EIS data were 5.5 × 10^?10 cm² s^?1 for lithiated (at a potential of 3.5 V) and 2.3 × 10^?9 cm² s^?1 for delithiated (at a potential 4.1 V) forms. CV evaluation gave close results: 3 × 10^?11 cm² s^?1 for anodic and 3.4 × 10^?11 cm² s^?1 for cathodic processes, respectively. The use of complex experimental measurement procedure for combined application of the EIS, PITT, and GITT methods allowed to obtain thermodynamic E,c dependence of Li₃V₂(PO₄)₃ electrode, which is not affected by polarization and heterogeneity of lithium concentration in the intercalate.     

Enhanced catalytic hydrogenation activity of Ni/reduced graphene oxide nanocomposite prepared by a solid-state method

A simple solid-state method has been applied to synthesize Ni/reduced graphene oxide (Ni/rGO) nanocomposite under ambient condition. Ni nanoparticles with size of 10–30 nm supported on reduced graphene oxide (rGO) nanosheets are obtained through one-pot solid-state co-reduction among nickel chloride, graphene oxide, and sodium borohydride. The Ni/rGO nanohybrid shows enhanced catalytic activity toward the reduction of p-nitrophenol (PNP) into p-aminophenol compared with Ni nanoparticles. The results of kinetic research display that the pseudo-first-order rate constant for hydrogenation reaction of PNP with Ni/rGO nanocomposite is 7.66 × 10^?3 s^?1, which is higher than that of Ni nanoparticles (4.48 × 10^?3 s^?1). It also presents superior turnover frequency (TOF, 5.36 h^?1) and lower activation energy (E_a, 29.65 kJ mol^?1) in the hydrogenation of PNP with Ni/rGO nanocomposite. Furthermore, composite catalyst can be magnetically separated and reused for five cycles. The large surface area and high electron transfer property of rGO support are beneficial for good catalytic performance of Ni/rGO nanocomposite. Our study demonstrates a simple approach to fabricate metal-rGO heterogeneous nanostructures with advanced functions.

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Selective Fluorescent Detection of Aspartic Acid and Glutamic Acid Employing Dansyl Hydrazine Dextran Conjugate

Highly water soluble polymer (DD) was prepared and evaluated for its fluorescence response towards various amino acids. The polymer consists of dansyl hydrazine unit conjugated into dextran template. The conjugation enhances higher water solubility of dansyl hydrazine moiety. Of screened amino acids, DD exhibited selective fluorescence quenching in the presence of aspartic acid (Asp) and glutamic acid (Glu). A plot of fluorescence intensity change of DD against the concentration of corresponding amino acids gave a good linear relationship in the range of 1?×?10^?4 M to 25?×?10^?3 M. This establishes DD as a potential polymeric sensor for selective sensing of Asp and Glu.

Weyl’s Type Estimates on the Eigenvalues of Critical Schrödinger Operators

We consider on a bounded domain \(\Omega \subset {\mathbb{R}}^N\) , the Schrödinger operator ? Δ ? V supplemented with Dirichlet boundary solutions. The potential V is either the critical inverse square potential V(x) = (N ? 2)²/4|x|^?2 or the critical borderline potential V(x) =  (1/4)dist(x, ?Ω)^?2. We present explicit asymptotic estimates on the eigenvalues of the critical Schrödinger operator in each case, based on recent results on improved Hardy–Sobolev type inequalities.     

Spectroscopic studies on the interaction of bovine serum albumin with ginkgolic acid: Binding characteristics and structural analysis

The interaction between ginkgolic acid (GA, C15:0) and bovine serum albumin (BSA) is investigated by several spectroscopic methodologies. At first, the binding characteristics of GA and BSA are determined by fluorescence emission spectra. It is showed that GA quenches the fluorescence of BSA and the static quenching constant K_LB is 11.7891×10⁴ L mol^?1 s^?1 at 297 K. GA and BSA form a 1:1 complex with a binding constant of 9.12×10⁵ L mol^?1. GA binds to the Sudlow's drug binding site II in BSA, and the binding distance between them is calculated as 1.63 nm based on the Förster theory. The thermodynamic parameters indicate that the interaction between BSA and GA is driven mainly by hydrophobic forces. On the other hand, structural analysis indicates that GA binding results in an increased hydrophobicity around the tryptophan residues of BSA as revealed by the synchronous fluorescence spectra, and a decrease in α-helix as revealed by the far-UV CD spectra. In addition, ANS, UV–vis and RLS experiments confirmed that GA binding causes a certain structural changes in BSA. These findings provide the binding information between BSA and GA, and may be helpful for pharmacokinetics and the design of dosage forms of GA.