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Thermodynamic studies on complexation of dopamine with gadolinium(III) in water–ethanol system
Journal of Molecular Liquids 156 (2010) 141–145
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Journal of Molecular Liquids j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / m o l l i q
Thermodynamic studies on complexation of dopamine with gadolinium(III) in water–ethanol system Azar Bagheri Gh ⁎ Department of Chemistry, Center Tehran Branch, Islamic Azad University, Tehran, Iran
a r t i c l e
i n f o
Article history: Received 15 September 2009 Received in revised form 7 July 2010 Accepted 9 July 2010 Available online 15 July 2010 Keywords: Gadolinium(III) Dopamine Complexation Mixed solvent Thermodynamic
a b s t r a c t The stability constant for complexation of gadolinium(III) with dopamine in mixed solvent systems of ethanol + water and free-energy changes have been determined spectro-photometrically with a temperature variation method in 0.2 mol dm− 3 sodium chloride as ionic medium employed at [(15, 25 and 35 ± 0.1) °C] at pH ranges of ~ 5 to ~ 7.5 with a high ratio of ligand to metal. The effect of solvent systems on protonation and complexation are discussed. Linear relationships are observed by plotting log K versus 1/D, where K and D are the stability and dielectric constants, respectively. © 2010 Elsevier B.V. All rights reserved.
1. Introduction Dopamine is a catecholamine neurotransmitter of the central nervous system (CNS). Dopamine agonists play an important role in the regulation of the central nervous–cardiovascular, renal, and hormonal systems through stimulation of dopaminergic (DA1 and DA2) and α- and β-adrenergic receptors. Besides neurotransmission, dopamine has other biological activities. Exogenous dopamine has important relevance in clinical medicine for elevating blood pressure, raising cardiac output and in the treatment of shock in acute renal and pulmonary failure [1,2]. An inverse relationship between the concentration of dopamine in CNS and tumor growth has been demonstrated in experimental animals [3]. Parkinson's disease is characterized by degeneration of the nigrostriatal dopaminergic system, which has an important role in the control of motor and associative functions. Although it is generally accepted that free radicals are involved in the neurodegenerative process of Parkinson's disease which takes place in the dopaminergic nigrostriatal neuronal system [4–8], the exact mechanism of neurodegeneration in vivo is still unknown. Scientists have long sought the mechanisms by which alcohol acts on the brain to modify behavior. An important finding is the demonstration that alcohol can affect the function of specific neurotransmitters [9]. Studies of neurotransmitters and the receptors to which they bind have provided data on both the structure and the mechanism of action of these molecules as well as clues to their role in
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behavior. However, the function of individual neurotransmitters and their receptors cannot entirely explain a syndrome as neurotransmitter systems to influence behavior. Alcohol has been shown to activate dopamine systems in certain areas of the brain through an interaction with glutamate receptors [10]. Interestingly endogenous opitate systems could cause the decrease in the acting of dopamine systems that occurs during alcohol withdrawal. Alcohol's depressant effect on neurons may be associated with some of the behavioral manifestations of intoxication: Alcohol consumption is initially accompanied by decreased attention, alterations in memory, mood changes, and drowsiness. Ethanol, used as part of a cosolvent system with water, has been demonstrated to increase penetration of a variety of drugs through the skin barrier [11–13]. Generally, nonelectrolyte or neutral drugs (such as digoxin, phenytoin, and the benzodiazepines) are dissolved in a nonaqueous or a cosolvent vehicle due to their poor solubility in water. If the drug is placed in an aqueous environment, it may form a precipitate, with concomitant loss of drug activity and/or danger to the patient. Hence, if the drug is dissolved in a water miscible solvent and one administers it slowly, dilution of the vehicle results in cosolvent fractions that maintain the drug in solution. The results of such studies may provide useful information in aiding in the Rational Drug Design, medicinal chemistry, biochemistry and molecular biology. The coordination chemistry of the rare earth metal ions can, with profit, be contrasted and compared with that of the d-type transition metal ions. Appreciably stable complex species, other than the hydrated cations themselves, are obtained only when the most strongly chelating ligands are used and, in particular, when these ligands contain highly electronegative donor atoms (e.g., oxygen).
142
A. Bagheri Gh / Journal of Molecular Liquids 156 (2010) 141–145
Neurotransmitters are frequently organic bases, which form adducts with systems of electron acceptors such as metal ions, proteins and components of protein by direct or indirect interactions. For example operation of neurotransmitters is distorted if they react with heavy metals such as Pb, Hg or lanthanides that frequently act as hard acids. The coordination chemistry of these compounds is complicated by their ability to act as ambidentate or bridging ligands [14,15]. In this paper we evaluate the stability constants and thermodynamic parameters for Gd3+ binding to dopamine in cosolvent systems of ethanol and water using a combination of potentiometric and spectrophotometric methods [16–18].
Spectrophotometric measurements were conducted using an UV–VIS Shimadzu 2101 spectrophotometer equipped with an Acermate 486 SX/25D computer and thermostatically matched 10-mm quartz cells. The dielectric constants, D, of mixed solvent systems of ethanol in water were measured by comparing the capacitance of a capacitor with and without the sample present (C and C0, respectively), using D = C/C0. Dielectric constant measurements were carried out using a Lurton-DM-9023 capacitance meter. In all cases, the procedure was repeated at least four times and the resulting average values and corresponding standard deviations are shown in the text and tables. 3. Results and discussion
2. Experimental 2.1. Materials Dopamine, gadolinium chloride, ethanol, sodium dihydrogen phosphate, disodium hydrogen phosphate and sodium chloride were supplied from Merck Chemical Company and were used without further purification. The NaOH solutions were prepared from titrasol solutions and their concentration was determined by several titrations with standard HCl. All dilute solutions were prepared from doubledistilled water with specific conductance equal to 1.3± 0.1 μΩ− 1 cm− 1. The dissociation constants were determined using the potentiometric technique and calculated using the Solver, Microsoft Excel 2000 powerful optimization package, to perform non-linear least-squares curve fitting [19]. Dissociation constants are given in Table 1 together with the values reported in the literature, which are in good agreement with those reported before.[20–22]. 2.2. Methods All measurements were carried out at [(15, 25 and 35 ± 0.1) °C] and at an ionic strength of 0.2 mol dm− 3 which was controlled with sodium chloride. The ligand concentrations were 1.2 mmol dm− 3 and the Gd3+ concentrations were 0.4, 0.6, and 1.2 mmol dm− 3 with ligand to Gd3+ molar ratios of 3, 2 and 1. The pH of the solutions was controlled with phosphate buffers. The method of determination of the stability constant based on the relationship, A = f (pH) was employed, on account of the high stability of the complexes studied [23]. A Horiba D-14 pH meter was employed for pH measurements. The hydrogen-ion concentrations were measured using an Ingold UO3234 glass electrode and an Ingold UO3236 calomel electrode. It is essential that the system be calibrated routinely for various solvent mixtures of known hydrogen-ion concentration [24–28].
Table 1 Average values of protonation constants for dopamine with standard deviations (is mentioned), in (x) water + (1 − x) ethanol at different temperatures and I = 0.2 mol dm− 3. x (molar fraction) t = 15 °C 1.000 0.955 0.930 0.901 t = 25 °C 1.000 0.955 0.930 0.901 t = 35 °C 1.000 0.955 0.930 0.901
log k3a
log k1a
pk13 + pk1
9.03 ± 0.01 9.06 ± 0.02 9.10 ± 0.01 9.14 ± 0.01
13.15 ± 0.01 13.16 ± 0.01 13.16 ± 0.01 13.18 ± 0.01
21.78 21.82 21.86 21.92
8.89 ± 0.02 8.94 ± 0.01 8.99 ± 0.01 9.03 ± 0.01
13.10 ± 0.02 13.10 ± 0.01 13.11 ± 0.01 13.12 ± 0.01
21.59 21.64 21.70 21.75
8.86 ± 0.02 8.91 ± 0.01 8.96 ± 0.01 8.98 ± 0.01
13.05 ± 0.02 13.06 ± 0.01 13.09 ± 0.01 13.09 ± 0.01
21.51 21.57 21.65 21.67
+ y − z)+ The complex MxHyL(nx formed is characterized by its z stoichiometry (x:y:z) where M and L represent the metal ion and the ligand, respectively. To determine the stability constant of the complexation or the protonation, Eq. (1) is defined by βxyz:
xM
n+
þ
−
ðnx + y−zÞ+
+ yH + zL ⇌Mx HY LZ
h ðnx βxyz = MX HY LZ
+ y−zÞ
i h
=M
n+
ix h
H
i
þ Y
ð1Þ
½L
− Z
ð2Þ
The protonation constants of dopamine have been used for computation of stability constants, βxyz. The protonation constants for a 1 mmol dm− 3 concentration ligand in water and in mixed solvent systems of ethanol and water were obtained from potentiometric titrations with 0.1 mol dm− 3 NaOH and employing a computer-programmed non-linear least-squares method [19]. Values of the constants obtained are listed in Table 1 and agree with those obtained from the literature (pKa1 = 8.89, pKa2 = 10.41, pKa3 = 13.1 in 25 °C) [20–22]. We assume that deprotonation occurs in the following order with increasing pH: the paraphenolic group, the ammonium group and then the second OH group for dopamine. The protonation constants are K1a, K2a, K3a. These values are listed in Table 1. The following equilibria are considered: k1 a − ⇌ HL
ð3Þ
þ − k2 a H + HL ⇌ H2 L
ð4Þ
k3 a þ þ H + H2 L⇌ H3 L
ð5Þ
þ
H +L
−2
The protonation constants are K1a, K2a, K3a. Absorbance measurements were made for solutions containing Gd (III) and dopamine with different molar ratios in pH of ~5 and ~ 7.5 in different solvent systems. Considering that absorbance is a function of pH, the values of the molar absorptivities of Gd(III), ε0, (and for dopamine, ε1) at different wavelengths and various dielectric constants are shown in Table 2. In order to determine ε1 and ε0, solutions are prepared by a similar method and conditions, but in the absence of metal and ligand ions as described, respectively. In order to determine ε2, the formation constant of the complex can be expressed as follows: 2+
GdðHLÞ
þ
+ 2H ⇌Gd
⌊
H
2+
KGdðHLÞ2+ = GdðHLÞ
3+
h
+ H3 L+ i2 h
⌋H = þ
ð6Þ
ih i þ 3+ Gd H3 L
ð7Þ
The absorbance at a wavelength is given by:
⌊
A = ε0 Gd
⌋ + ε ⌊H L ⌋ + ε ⌊GdðHLÞ ⌋
3+
1
3
þ
2+
2
ð8Þ
A. Bagheri Gh / Journal of Molecular Liquids 156 (2010) 141–145
And consequent:
Table 2 4 Values of molar absorptivities of Gd (× 10−4) and [Gd(HL)+ 2 ] (×10− ).
⌊
λ
λ(nm)
x
ε
280
275
270
265
260
ε0 ε3 ε0 ε3 ε0 ε3 ε0 ε3
261 1737.3 639 2195.1 1012 2421 1228 2645.8
393 3268.3 650 3149.7 1024 3267.4 1236 3554.7
837 3635.8 660 4184.5 1038 4580.9 1242 4803.1
562 4082.8 699 5081.1 1062 5653.1 1362 5840.1
539 4439 976 5290.5 1121 5710.5 1368 5969.2
ε0 ε3 ε0 ε3 ε0 ε3 ε0 ε3
256 1645.9 404 2189.7 671 2251 866 2587.8
320 2569.1 608 2663.7 686 2949.2 993 3374.7
365 3564.7 614 4145.7 703 4378.7 1200 4769.9
379 4057.1 623 5064.8 707 5295.8 1218 5799
407 4278.8 653 5238.9 740 5395.5 1224 5862.8
t = 15 °C 1.000 0.955 0.930 0.901
t = 25 °C 1.000 0.955 0.930 0.901
ε0 ε3 ε0 ε3 ε0 ε3 ε0 ε3
0.955 0.930 0.901
100 1630 307 2005.6 632 2231 704 2552.3
223 2369.1 317 2606.3 657 2886.7 831 2886.7
226 3453.4 409 3842.9 673 4069.5 856 4551
240 4012.4 600 4887.8 681 5065.7 861 5386.5
252 4269.3 590 4957.3 700 5391.2 871 5392.4
where ε0, ε1, ε2 are the molar absorptivities of the Gd(III) ion and dopamine and complex, respectively. Thus, considering material balance, the equilibrium constant for formation of the complex can be expressed as follows: A + ε1 CGd3+ + ε0 CH3 Lþ = CGd3+ n ðε0 + ε1 −ε2 Þ −A + ε1 CH3 Lþ + ε0 CGd3+ H þ = ε2 + H CGd3+ A−ε0 CGd3+ −ε2 CHþ3 L + ε0 CH3 Lþ KGd ðHLÞ2+
ð9Þ
H The values of KGd were determined from the intercept of the ðHLÞ2+ (Y) against straight line plots of A + 1 CGd3+ + ε0 CH3 Lþ = CGd3+ εþ −A + ε1 CH3 Lþ + ε0 CGd3+ ½H n = CGd3+ (X). The intercept of linear fit yields ε2. In the equilibrium reaction of complex formation is: þ
þ
2+
GdðHLÞ2 + 2H ⇌GdðHLÞ
+ H3 L
þ
ð10Þ
The formation constant of the complex can be expressed as follows: h
H
þ
KGdðHLÞþ = GdðHLÞ2
ih
2
H
þ
i2 h
= GdðHLÞ
2+
ih
H3 L
þ
i
ð11Þ
With attention to ligand absorbance, the absorbance at a wavelength is given by:
⌊
⌋ + ε ⌊H L ⌋ + ε ⌊GdðHLÞ ⌋ + ε ⌊GdðHLÞ ⌋
3+
A = ε0 Gd
1
3
þ
[Gd3+] is negligible: h i 3+ ≈0 Gd
2+
2
3
þ 2
ð12Þ
ð13Þ
⌋ + ε ⌊GdðHLÞ ⌋ + ε ⌊GdðHLÞ ⌋
þ
A = ε1 H3 L
þ 2
2+
2
3
ð14Þ
Where ε0, ε1, ε2 and ε3 are the molar absorptivities of the Gd(III) ion, dopamine and their complexes. For the molar balance of gadolinium and dopamine:
⌊Gd ⌋ = ⌊GdðHLÞ ⌋ + ⌊GdðHLÞ ⌋ 3+
⌊H L ⌋ = C 3
þ
þ 2
2+
H3 Lþ
⌊
⌋ + 2⌊GdðHLÞ ⌋ þ 2
2+
+ GdðHLÞ
ð15Þ ð16Þ
Where [Gd3+] and [H3L+]are the total concentrations of Gd3+ and dopamine. Thus, the equilibrium constant for formation of the complex can be expressed as follows:
−A + ε1 CH3 L þ −2ε1 CGd3+ = −ε3 +
t = 35 °C 1.000
143
=C
Gd3+
2 ðε3 −ε2 −ε1 Þ A−ε1 CH3 Lþ + ε1 CGd3+ −ε2 CGd3+ Hþ H þ þ KGd ðHLÞþ ε3 CH3 L −ε2 CH3 L −A−ε3 CGd3+ + 2ε2 CGd3+ CGd3+
½
2
ð17Þ Considering that A is a function of pH, the values of molar absorptivities, are shown in Table 2. The values of K H were Gd(HL) 2+ determined from the intercept of the straight line plots of − A + ε1CH3L+ − 2ε1CGd3+ (Y) against (A − ε1CH3L+ + ε1CGd3+ − ε2CGd3+ ) [H+]2 / CGd3+ (X) and are shown in Table 1. The intercept of the lines yields ε3. In order to properly interpret the overall stability constants, we must consider the form of the ligand chelating to the metal ion. In the case of dopamine pka3 corresponds almost exclusively to ionization of the second phenolic group. As vertified by several techniques, the macroconstants K1a and K2a cannot be assigned exclusively to the first phenolic and ammonium group deprotonation constants but are mixtures of them. Kiss et al. [20–22] define the microscopic acidity constants for the first two deprotonations. They approximate its concentration by estimating the microconstant k13 for loss of the second phenolic proton from the microspecies with a protonated ammonium group. They correct pK3 assigned exclusively to the second phenolic ionization in the molecule with a deprotonated amino group by the difference for the ligand according to pK13 = pK3 − (pk21 − pK1). The sum pK1 + pk13 is now used to calculate the concentration of the microspecies with two anionic phenolates and protonated ammonium group.
Table 3 H + Average values of log K+ Gd(HL)2, log K Gd(HL)2 with standard deviations (is mentioned), in (x) water + (1 − x) ethanol at different temperatures and I = 0.2 mol dm− 3. x (molar fraction) t = 15 °C 1.000 0.955 0.930 0.901 t = 25 °C 1.000 0.955 0.930 0.901 t = 35 °C 1.000 0.955 0.930 0.901
log K+ Gd(HL)2
log KHGd(HL)+ 2
52.28 ± 0.01 52.82 ± 0.03 52.99 ± 0.02 53.81 ± 0.01
7.92 8.30 8.35 8.48
51.88 ± 0.01 52.48 ± 0.02 52.86 ± 0.01 53.79 ± 0.01
7.90 8.28 8.30 8.43
51.46 ± 0.03 52.36 ± 0.02 52.37 ± 0.01 52.40 ± 0.02
7.64 8.26 8.23 8.20
144
A. Bagheri Gh / Journal of Molecular Liquids 156 (2010) 141–145 Table 4 Values ΔG° and ΔS° of gadolinium with dopamine complex formation in aqueous and mixed solvent systems at different temperatures and I = 0.2 mol dm− 3. x
Fig. 1. log K + Gd(HL)2 versus 1/D (= 0.0122, 0.0131, 0.0137, 0.0143) for (x) water + (1 − x) ethanol at 25 °C.
The sum pK1 + pk13 is now used to calculate the concentration of the microspecies with two anionic phenolates and protonated ammonium group. The absorbance of Gd(HL) + 2 at different pH and wavelengths in ethanol are listed in Table 2. The stability constant of the Gd(HL)+ 2 complex was calculated by combining the protonation constants of dopamine with the formation constants of the complexes (Table 3) þ
H
þ
log10 KGd ðHLÞ2 = log10 KGdðHLÞ 2 + 2ðpK13 + pK1 Þ
ð18Þ
The values of the formation constants for the rare earth complexes which have been investigated since 1955 for organic ligands and 1956 for inorganic liganic ligands. The significance of electronic configuration follows from the following considerations. The stabilities of coordination compounds of the d-type transition metal ions are related to participation of the d electrons in the metal-ligand bond through hybridization of metal electronic orbitals with appropriate ligand orbitals. The rare earth metal ions differ from each other in the number of electrons in the 4f orbitals, which orbitals are effectively shielded from interaction with ligand orbitals by electrons in the 5 s and 5p orbitals. If hybridization is to occur, it must of necessity involve normally unoccupied higher-energy orbitals (e.g., 5d, 6 s, 6p), and hybridization of this type can be expected only with the most strongly coordinating ligands. Significant cation-ligand attractions are thus largely electrostatic in character, and the complex species formed by these cations compare more closely with those derived from the calcium, strontium, and barium ions than with those derived from the d-type transition metal ions [29–31]. These cations (d0, with rare gas cores) are thus of the A-type [31]. The rare earth metal ions, in any state of oxidation, are large by comparison with cations that give the most stable complexes, and the change in size with increasing atomic number is not substantial.
t = 15 °C 1.000 0.955 0.930 0.901 t = 25 °C 1.000 0.955 0.930 0.901 t = 35 °C 1.000 0.955 0.930 0.901
−ΔG°, J/mol
ΔS°, J/mol k
287,916.08 ± 0.01 290,889.77 ± 0.03 291,803.97 ± 0.02 296,341.89 ± 0.01
1012.65 ± 0.01 1022.97 ± 0.03 1026.15 ± 0.02 1041.90 ± 0.01
295,612.20 ± 0.01 299,052.85 ± 0.02 301,217.42 ± 0.01 306,545.43 ± 0.01
1004.49 ± 0.01 1016.04 ± 0.02 1023.30 ± 0.01 1041.18 ± 0.01
303,080.75 ± 0.03 308,381.55 ± 0.02 308,440.45 ± 0.01 308,617.14 ± 0.01
996.13 ± 0.03 1013.34 ± 0.02 1013.53 ± 0.01 1014.10 ± 0.01
Some macroscopic properties of solvents are the dielectric permitivity (εT), dipole moment (μ) and refractive index (nD) and microscopic parameters are moment (μ) and Kamlet–Taft parameters of dipolarity/polarizability (π*), hydrogen-bond EN T acceptor basicity (β) and hydrogen-bond donor acidity (α). Water and alcohols are dipolar and hydrogen-bond acids and bases. The dipolarity (π*) and hydrogen-bond donor acidity (α) decrease in order water N alcohol, and therefore EN T and the dielectric permittivity decrease in the same order. However, the hydrogen-bond acceptor basicity (β) increases in the same order. Solvent effects on acid–base phenomena in amphiprotic media of intermediate and high dielectric constant (such as methanol and ethanol) are often successfully interpreted in terms of changes in the dielectric constant (electrostatic effects) and changes in the basicity (non-electrostatic effects). Accordingly, a lowering of the dielectric constant due to the addition of ethanol may have little effect on the basicity of the compound under investigation. Water is substituted by ethanol which has a lower dielectric constant. Thus, the electrostatic force of attraction between ions of opposite charge is reduced. Adding ethanol decreases the dielectric constant of solution, resulting in a greater attraction force and hence larger formation and protonation and formation constants. Enthalpy changes were obtained by plotting log K versus 1/T. Fig. 1 represents the linear relation between log K of the complex and 1/D of the solvent in the ethanol and water system, where D is the dielectric constant of system. The fact that the linear plots of the obtained values of free-energy changes, as a function of 1/D show that our results agree with the above speculation (see Fig. 2 and Table 4). Acknowledgement This work was supported by the Chemistry Department of Science and Research Branch of the Islamic Azad University. References
Fig. 2. −ΔG° versus 1/D (= 0.0122, 0.0131, 0.0137, 0.0143) for (x) water + (1 − x) ethanol at 25 °C.
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Contents lists available at ScienceDirect
Journal of Molecular Liquids j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / m o l l i q
Thermodynamic studies on complexation of dopamine with gadolinium(III) in water–ethanol system Azar Bagheri Gh ⁎ Department of Chemistry, Center Tehran Branch, Islamic Azad University, Tehran, Iran
a r t i c l e
i n f o
Article history: Received 15 September 2009 Received in revised form 7 July 2010 Accepted 9 July 2010 Available online 15 July 2010 Keywords: Gadolinium(III) Dopamine Complexation Mixed solvent Thermodynamic
a b s t r a c t The stability constant for complexation of gadolinium(III) with dopamine in mixed solvent systems of ethanol + water and free-energy changes have been determined spectro-photometrically with a temperature variation method in 0.2 mol dm− 3 sodium chloride as ionic medium employed at [(15, 25 and 35 ± 0.1) °C] at pH ranges of ~ 5 to ~ 7.5 with a high ratio of ligand to metal. The effect of solvent systems on protonation and complexation are discussed. Linear relationships are observed by plotting log K versus 1/D, where K and D are the stability and dielectric constants, respectively. © 2010 Elsevier B.V. All rights reserved.
1. Introduction Dopamine is a catecholamine neurotransmitter of the central nervous system (CNS). Dopamine agonists play an important role in the regulation of the central nervous–cardiovascular, renal, and hormonal systems through stimulation of dopaminergic (DA1 and DA2) and α- and β-adrenergic receptors. Besides neurotransmission, dopamine has other biological activities. Exogenous dopamine has important relevance in clinical medicine for elevating blood pressure, raising cardiac output and in the treatment of shock in acute renal and pulmonary failure [1,2]. An inverse relationship between the concentration of dopamine in CNS and tumor growth has been demonstrated in experimental animals [3]. Parkinson's disease is characterized by degeneration of the nigrostriatal dopaminergic system, which has an important role in the control of motor and associative functions. Although it is generally accepted that free radicals are involved in the neurodegenerative process of Parkinson's disease which takes place in the dopaminergic nigrostriatal neuronal system [4–8], the exact mechanism of neurodegeneration in vivo is still unknown. Scientists have long sought the mechanisms by which alcohol acts on the brain to modify behavior. An important finding is the demonstration that alcohol can affect the function of specific neurotransmitters [9]. Studies of neurotransmitters and the receptors to which they bind have provided data on both the structure and the mechanism of action of these molecules as well as clues to their role in
⁎ Tel.: + 98 21 88372691; fax: + 98 21 88385777. E-mail address: [email protected]. 0167-7322/$ – see front matter © 2010 Elsevier B.V. All rights reserved. doi:10.1016/j.molliq.2010.07.002
behavior. However, the function of individual neurotransmitters and their receptors cannot entirely explain a syndrome as neurotransmitter systems to influence behavior. Alcohol has been shown to activate dopamine systems in certain areas of the brain through an interaction with glutamate receptors [10]. Interestingly endogenous opitate systems could cause the decrease in the acting of dopamine systems that occurs during alcohol withdrawal. Alcohol's depressant effect on neurons may be associated with some of the behavioral manifestations of intoxication: Alcohol consumption is initially accompanied by decreased attention, alterations in memory, mood changes, and drowsiness. Ethanol, used as part of a cosolvent system with water, has been demonstrated to increase penetration of a variety of drugs through the skin barrier [11–13]. Generally, nonelectrolyte or neutral drugs (such as digoxin, phenytoin, and the benzodiazepines) are dissolved in a nonaqueous or a cosolvent vehicle due to their poor solubility in water. If the drug is placed in an aqueous environment, it may form a precipitate, with concomitant loss of drug activity and/or danger to the patient. Hence, if the drug is dissolved in a water miscible solvent and one administers it slowly, dilution of the vehicle results in cosolvent fractions that maintain the drug in solution. The results of such studies may provide useful information in aiding in the Rational Drug Design, medicinal chemistry, biochemistry and molecular biology. The coordination chemistry of the rare earth metal ions can, with profit, be contrasted and compared with that of the d-type transition metal ions. Appreciably stable complex species, other than the hydrated cations themselves, are obtained only when the most strongly chelating ligands are used and, in particular, when these ligands contain highly electronegative donor atoms (e.g., oxygen).
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A. Bagheri Gh / Journal of Molecular Liquids 156 (2010) 141–145
Neurotransmitters are frequently organic bases, which form adducts with systems of electron acceptors such as metal ions, proteins and components of protein by direct or indirect interactions. For example operation of neurotransmitters is distorted if they react with heavy metals such as Pb, Hg or lanthanides that frequently act as hard acids. The coordination chemistry of these compounds is complicated by their ability to act as ambidentate or bridging ligands [14,15]. In this paper we evaluate the stability constants and thermodynamic parameters for Gd3+ binding to dopamine in cosolvent systems of ethanol and water using a combination of potentiometric and spectrophotometric methods [16–18].
Spectrophotometric measurements were conducted using an UV–VIS Shimadzu 2101 spectrophotometer equipped with an Acermate 486 SX/25D computer and thermostatically matched 10-mm quartz cells. The dielectric constants, D, of mixed solvent systems of ethanol in water were measured by comparing the capacitance of a capacitor with and without the sample present (C and C0, respectively), using D = C/C0. Dielectric constant measurements were carried out using a Lurton-DM-9023 capacitance meter. In all cases, the procedure was repeated at least four times and the resulting average values and corresponding standard deviations are shown in the text and tables. 3. Results and discussion
2. Experimental 2.1. Materials Dopamine, gadolinium chloride, ethanol, sodium dihydrogen phosphate, disodium hydrogen phosphate and sodium chloride were supplied from Merck Chemical Company and were used without further purification. The NaOH solutions were prepared from titrasol solutions and their concentration was determined by several titrations with standard HCl. All dilute solutions were prepared from doubledistilled water with specific conductance equal to 1.3± 0.1 μΩ− 1 cm− 1. The dissociation constants were determined using the potentiometric technique and calculated using the Solver, Microsoft Excel 2000 powerful optimization package, to perform non-linear least-squares curve fitting [19]. Dissociation constants are given in Table 1 together with the values reported in the literature, which are in good agreement with those reported before.[20–22]. 2.2. Methods All measurements were carried out at [(15, 25 and 35 ± 0.1) °C] and at an ionic strength of 0.2 mol dm− 3 which was controlled with sodium chloride. The ligand concentrations were 1.2 mmol dm− 3 and the Gd3+ concentrations were 0.4, 0.6, and 1.2 mmol dm− 3 with ligand to Gd3+ molar ratios of 3, 2 and 1. The pH of the solutions was controlled with phosphate buffers. The method of determination of the stability constant based on the relationship, A = f (pH) was employed, on account of the high stability of the complexes studied [23]. A Horiba D-14 pH meter was employed for pH measurements. The hydrogen-ion concentrations were measured using an Ingold UO3234 glass electrode and an Ingold UO3236 calomel electrode. It is essential that the system be calibrated routinely for various solvent mixtures of known hydrogen-ion concentration [24–28].
Table 1 Average values of protonation constants for dopamine with standard deviations (is mentioned), in (x) water + (1 − x) ethanol at different temperatures and I = 0.2 mol dm− 3. x (molar fraction) t = 15 °C 1.000 0.955 0.930 0.901 t = 25 °C 1.000 0.955 0.930 0.901 t = 35 °C 1.000 0.955 0.930 0.901
log k3a
log k1a
pk13 + pk1
9.03 ± 0.01 9.06 ± 0.02 9.10 ± 0.01 9.14 ± 0.01
13.15 ± 0.01 13.16 ± 0.01 13.16 ± 0.01 13.18 ± 0.01
21.78 21.82 21.86 21.92
8.89 ± 0.02 8.94 ± 0.01 8.99 ± 0.01 9.03 ± 0.01
13.10 ± 0.02 13.10 ± 0.01 13.11 ± 0.01 13.12 ± 0.01
21.59 21.64 21.70 21.75
8.86 ± 0.02 8.91 ± 0.01 8.96 ± 0.01 8.98 ± 0.01
13.05 ± 0.02 13.06 ± 0.01 13.09 ± 0.01 13.09 ± 0.01
21.51 21.57 21.65 21.67
+ y − z)+ The complex MxHyL(nx formed is characterized by its z stoichiometry (x:y:z) where M and L represent the metal ion and the ligand, respectively. To determine the stability constant of the complexation or the protonation, Eq. (1) is defined by βxyz:
xM
n+
þ
−
ðnx + y−zÞ+
+ yH + zL ⇌Mx HY LZ
h ðnx βxyz = MX HY LZ
+ y−zÞ
i h
=M
n+
ix h
H
i
þ Y
ð1Þ
½L
− Z
ð2Þ
The protonation constants of dopamine have been used for computation of stability constants, βxyz. The protonation constants for a 1 mmol dm− 3 concentration ligand in water and in mixed solvent systems of ethanol and water were obtained from potentiometric titrations with 0.1 mol dm− 3 NaOH and employing a computer-programmed non-linear least-squares method [19]. Values of the constants obtained are listed in Table 1 and agree with those obtained from the literature (pKa1 = 8.89, pKa2 = 10.41, pKa3 = 13.1 in 25 °C) [20–22]. We assume that deprotonation occurs in the following order with increasing pH: the paraphenolic group, the ammonium group and then the second OH group for dopamine. The protonation constants are K1a, K2a, K3a. These values are listed in Table 1. The following equilibria are considered: k1 a − ⇌ HL
ð3Þ
þ − k2 a H + HL ⇌ H2 L
ð4Þ
k3 a þ þ H + H2 L⇌ H3 L
ð5Þ
þ
H +L
−2
The protonation constants are K1a, K2a, K3a. Absorbance measurements were made for solutions containing Gd (III) and dopamine with different molar ratios in pH of ~5 and ~ 7.5 in different solvent systems. Considering that absorbance is a function of pH, the values of the molar absorptivities of Gd(III), ε0, (and for dopamine, ε1) at different wavelengths and various dielectric constants are shown in Table 2. In order to determine ε1 and ε0, solutions are prepared by a similar method and conditions, but in the absence of metal and ligand ions as described, respectively. In order to determine ε2, the formation constant of the complex can be expressed as follows: 2+
GdðHLÞ
þ
+ 2H ⇌Gd
⌊
H
2+
KGdðHLÞ2+ = GdðHLÞ
3+
h
+ H3 L+ i2 h
⌋H = þ
ð6Þ
ih i þ 3+ Gd H3 L
ð7Þ
The absorbance at a wavelength is given by:
⌊
A = ε0 Gd
⌋ + ε ⌊H L ⌋ + ε ⌊GdðHLÞ ⌋
3+
1
3
þ
2+
2
ð8Þ
A. Bagheri Gh / Journal of Molecular Liquids 156 (2010) 141–145
And consequent:
Table 2 4 Values of molar absorptivities of Gd (× 10−4) and [Gd(HL)+ 2 ] (×10− ).
⌊
λ
λ(nm)
x
ε
280
275
270
265
260
ε0 ε3 ε0 ε3 ε0 ε3 ε0 ε3
261 1737.3 639 2195.1 1012 2421 1228 2645.8
393 3268.3 650 3149.7 1024 3267.4 1236 3554.7
837 3635.8 660 4184.5 1038 4580.9 1242 4803.1
562 4082.8 699 5081.1 1062 5653.1 1362 5840.1
539 4439 976 5290.5 1121 5710.5 1368 5969.2
ε0 ε3 ε0 ε3 ε0 ε3 ε0 ε3
256 1645.9 404 2189.7 671 2251 866 2587.8
320 2569.1 608 2663.7 686 2949.2 993 3374.7
365 3564.7 614 4145.7 703 4378.7 1200 4769.9
379 4057.1 623 5064.8 707 5295.8 1218 5799
407 4278.8 653 5238.9 740 5395.5 1224 5862.8
t = 15 °C 1.000 0.955 0.930 0.901
t = 25 °C 1.000 0.955 0.930 0.901
ε0 ε3 ε0 ε3 ε0 ε3 ε0 ε3
0.955 0.930 0.901
100 1630 307 2005.6 632 2231 704 2552.3
223 2369.1 317 2606.3 657 2886.7 831 2886.7
226 3453.4 409 3842.9 673 4069.5 856 4551
240 4012.4 600 4887.8 681 5065.7 861 5386.5
252 4269.3 590 4957.3 700 5391.2 871 5392.4
where ε0, ε1, ε2 are the molar absorptivities of the Gd(III) ion and dopamine and complex, respectively. Thus, considering material balance, the equilibrium constant for formation of the complex can be expressed as follows: A + ε1 CGd3+ + ε0 CH3 Lþ = CGd3+ n ðε0 + ε1 −ε2 Þ −A + ε1 CH3 Lþ + ε0 CGd3+ H þ = ε2 + H CGd3+ A−ε0 CGd3+ −ε2 CHþ3 L + ε0 CH3 Lþ KGd ðHLÞ2+
ð9Þ
H The values of KGd were determined from the intercept of the ðHLÞ2+ (Y) against straight line plots of A + 1 CGd3+ + ε0 CH3 Lþ = CGd3+ εþ −A + ε1 CH3 Lþ + ε0 CGd3+ ½H n = CGd3+ (X). The intercept of linear fit yields ε2. In the equilibrium reaction of complex formation is: þ
þ
2+
GdðHLÞ2 + 2H ⇌GdðHLÞ
+ H3 L
þ
ð10Þ
The formation constant of the complex can be expressed as follows: h
H
þ
KGdðHLÞþ = GdðHLÞ2
ih
2
H
þ
i2 h
= GdðHLÞ
2+
ih
H3 L
þ
i
ð11Þ
With attention to ligand absorbance, the absorbance at a wavelength is given by:
⌊
⌋ + ε ⌊H L ⌋ + ε ⌊GdðHLÞ ⌋ + ε ⌊GdðHLÞ ⌋
3+
A = ε0 Gd
1
3
þ
[Gd3+] is negligible: h i 3+ ≈0 Gd
2+
2
3
þ 2
ð12Þ
ð13Þ
⌋ + ε ⌊GdðHLÞ ⌋ + ε ⌊GdðHLÞ ⌋
þ
A = ε1 H3 L
þ 2
2+
2
3
ð14Þ
Where ε0, ε1, ε2 and ε3 are the molar absorptivities of the Gd(III) ion, dopamine and their complexes. For the molar balance of gadolinium and dopamine:
⌊Gd ⌋ = ⌊GdðHLÞ ⌋ + ⌊GdðHLÞ ⌋ 3+
⌊H L ⌋ = C 3
þ
þ 2
2+
H3 Lþ
⌊
⌋ + 2⌊GdðHLÞ ⌋ þ 2
2+
+ GdðHLÞ
ð15Þ ð16Þ
Where [Gd3+] and [H3L+]are the total concentrations of Gd3+ and dopamine. Thus, the equilibrium constant for formation of the complex can be expressed as follows:
−A + ε1 CH3 L þ −2ε1 CGd3+ = −ε3 +
t = 35 °C 1.000
143
=C
Gd3+
2 ðε3 −ε2 −ε1 Þ A−ε1 CH3 Lþ + ε1 CGd3+ −ε2 CGd3+ Hþ H þ þ KGd ðHLÞþ ε3 CH3 L −ε2 CH3 L −A−ε3 CGd3+ + 2ε2 CGd3+ CGd3+
½
2
ð17Þ Considering that A is a function of pH, the values of molar absorptivities, are shown in Table 2. The values of K H were Gd(HL) 2+ determined from the intercept of the straight line plots of − A + ε1CH3L+ − 2ε1CGd3+ (Y) against (A − ε1CH3L+ + ε1CGd3+ − ε2CGd3+ ) [H+]2 / CGd3+ (X) and are shown in Table 1. The intercept of the lines yields ε3. In order to properly interpret the overall stability constants, we must consider the form of the ligand chelating to the metal ion. In the case of dopamine pka3 corresponds almost exclusively to ionization of the second phenolic group. As vertified by several techniques, the macroconstants K1a and K2a cannot be assigned exclusively to the first phenolic and ammonium group deprotonation constants but are mixtures of them. Kiss et al. [20–22] define the microscopic acidity constants for the first two deprotonations. They approximate its concentration by estimating the microconstant k13 for loss of the second phenolic proton from the microspecies with a protonated ammonium group. They correct pK3 assigned exclusively to the second phenolic ionization in the molecule with a deprotonated amino group by the difference for the ligand according to pK13 = pK3 − (pk21 − pK1). The sum pK1 + pk13 is now used to calculate the concentration of the microspecies with two anionic phenolates and protonated ammonium group.
Table 3 H + Average values of log K+ Gd(HL)2, log K Gd(HL)2 with standard deviations (is mentioned), in (x) water + (1 − x) ethanol at different temperatures and I = 0.2 mol dm− 3. x (molar fraction) t = 15 °C 1.000 0.955 0.930 0.901 t = 25 °C 1.000 0.955 0.930 0.901 t = 35 °C 1.000 0.955 0.930 0.901
log K+ Gd(HL)2
log KHGd(HL)+ 2
52.28 ± 0.01 52.82 ± 0.03 52.99 ± 0.02 53.81 ± 0.01
7.92 8.30 8.35 8.48
51.88 ± 0.01 52.48 ± 0.02 52.86 ± 0.01 53.79 ± 0.01
7.90 8.28 8.30 8.43
51.46 ± 0.03 52.36 ± 0.02 52.37 ± 0.01 52.40 ± 0.02
7.64 8.26 8.23 8.20
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A. Bagheri Gh / Journal of Molecular Liquids 156 (2010) 141–145 Table 4 Values ΔG° and ΔS° of gadolinium with dopamine complex formation in aqueous and mixed solvent systems at different temperatures and I = 0.2 mol dm− 3. x
Fig. 1. log K + Gd(HL)2 versus 1/D (= 0.0122, 0.0131, 0.0137, 0.0143) for (x) water + (1 − x) ethanol at 25 °C.
The sum pK1 + pk13 is now used to calculate the concentration of the microspecies with two anionic phenolates and protonated ammonium group. The absorbance of Gd(HL) + 2 at different pH and wavelengths in ethanol are listed in Table 2. The stability constant of the Gd(HL)+ 2 complex was calculated by combining the protonation constants of dopamine with the formation constants of the complexes (Table 3) þ
H
þ
log10 KGd ðHLÞ2 = log10 KGdðHLÞ 2 + 2ðpK13 + pK1 Þ
ð18Þ
The values of the formation constants for the rare earth complexes which have been investigated since 1955 for organic ligands and 1956 for inorganic liganic ligands. The significance of electronic configuration follows from the following considerations. The stabilities of coordination compounds of the d-type transition metal ions are related to participation of the d electrons in the metal-ligand bond through hybridization of metal electronic orbitals with appropriate ligand orbitals. The rare earth metal ions differ from each other in the number of electrons in the 4f orbitals, which orbitals are effectively shielded from interaction with ligand orbitals by electrons in the 5 s and 5p orbitals. If hybridization is to occur, it must of necessity involve normally unoccupied higher-energy orbitals (e.g., 5d, 6 s, 6p), and hybridization of this type can be expected only with the most strongly coordinating ligands. Significant cation-ligand attractions are thus largely electrostatic in character, and the complex species formed by these cations compare more closely with those derived from the calcium, strontium, and barium ions than with those derived from the d-type transition metal ions [29–31]. These cations (d0, with rare gas cores) are thus of the A-type [31]. The rare earth metal ions, in any state of oxidation, are large by comparison with cations that give the most stable complexes, and the change in size with increasing atomic number is not substantial.
t = 15 °C 1.000 0.955 0.930 0.901 t = 25 °C 1.000 0.955 0.930 0.901 t = 35 °C 1.000 0.955 0.930 0.901
−ΔG°, J/mol
ΔS°, J/mol k
287,916.08 ± 0.01 290,889.77 ± 0.03 291,803.97 ± 0.02 296,341.89 ± 0.01
1012.65 ± 0.01 1022.97 ± 0.03 1026.15 ± 0.02 1041.90 ± 0.01
295,612.20 ± 0.01 299,052.85 ± 0.02 301,217.42 ± 0.01 306,545.43 ± 0.01
1004.49 ± 0.01 1016.04 ± 0.02 1023.30 ± 0.01 1041.18 ± 0.01
303,080.75 ± 0.03 308,381.55 ± 0.02 308,440.45 ± 0.01 308,617.14 ± 0.01
996.13 ± 0.03 1013.34 ± 0.02 1013.53 ± 0.01 1014.10 ± 0.01
Some macroscopic properties of solvents are the dielectric permitivity (εT), dipole moment (μ) and refractive index (nD) and microscopic parameters are moment (μ) and Kamlet–Taft parameters of dipolarity/polarizability (π*), hydrogen-bond EN T acceptor basicity (β) and hydrogen-bond donor acidity (α). Water and alcohols are dipolar and hydrogen-bond acids and bases. The dipolarity (π*) and hydrogen-bond donor acidity (α) decrease in order water N alcohol, and therefore EN T and the dielectric permittivity decrease in the same order. However, the hydrogen-bond acceptor basicity (β) increases in the same order. Solvent effects on acid–base phenomena in amphiprotic media of intermediate and high dielectric constant (such as methanol and ethanol) are often successfully interpreted in terms of changes in the dielectric constant (electrostatic effects) and changes in the basicity (non-electrostatic effects). Accordingly, a lowering of the dielectric constant due to the addition of ethanol may have little effect on the basicity of the compound under investigation. Water is substituted by ethanol which has a lower dielectric constant. Thus, the electrostatic force of attraction between ions of opposite charge is reduced. Adding ethanol decreases the dielectric constant of solution, resulting in a greater attraction force and hence larger formation and protonation and formation constants. Enthalpy changes were obtained by plotting log K versus 1/T. Fig. 1 represents the linear relation between log K of the complex and 1/D of the solvent in the ethanol and water system, where D is the dielectric constant of system. The fact that the linear plots of the obtained values of free-energy changes, as a function of 1/D show that our results agree with the above speculation (see Fig. 2 and Table 4). Acknowledgement This work was supported by the Chemistry Department of Science and Research Branch of the Islamic Azad University. References
Fig. 2. −ΔG° versus 1/D (= 0.0122, 0.0131, 0.0137, 0.0143) for (x) water + (1 − x) ethanol at 25 °C.
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