On the Interaction Between Nicotine and Metal(II) Ions

On the Interaction Between Nicotine and Metal(II) Ions in Aqueous Solutions

C. Manfredi, S. Vero, E. Vasca, D. Perrotta, M. Trifuoggi, I. Sorrentino & D. Ferri Journal of Solution Chemistry ISSN 0095-9782 Volume 45 Number 7 J Solution Chem (2016) 45:971-989 DOI 10.1007/s10953-016-0483-9

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Author's personal copy J Solution Chem (2016) 45:971–989 DOI 10.1007/s10953-016-0483-9

On the Interaction Between Nicotine and Metal(II) Ions in Aqueous Solutions C. Manfredi1 • S. Vero1 • E. Vasca2 • D. Perrotta1 M. Trifuoggi1 • I. Sorrentino1 • D. Ferri1

•

Received: 2 August 2015 / Accepted: 6 December 2015 / Published online: 14 June 2016 Ó Springer Science+Business Media New York 2016

Abstract A chemical investigation of the interaction mechanisms of nicotine with the metal(II) ions Pb2þ , Fe2þ , and Cu2þ is reported. The complex formation between nicotine and metal(II) has been investigated at 25.00 0.02 C, in constant ionic medium (as sodium perchlorate, or sodium chloride), by UV/Vis spectrophotometric and potentiometric methods. The experimental method consists of coulometric or volumetric titrations. The protolysis constants of nicotine have been determined under the same experimental conditions. The pH investigated spans between 3 and 10. By using the specific ion interaction theory the conditional constants of nicotine have been extrapolated at zero ionic strength. The results of the graphical and numerical methods adopted indicate, for all the systems investigated, the formation of a predominating Me(II)/nicotine mononuclear complexes. Keywords Nicotine Hydrolysis Equilibrium analysis Metal(II)/nicotine complexes Potentiometry UV/Vis absorption

1 Introduction Neurodegenerative diseases like Alzheimer’s and Parkinson’s disease are associated with elevated levels of metals such as iron, copper, and zinc and consequentially high levels of oxidative stress [1–3]. Given the multi-factorial nature of these diseases, it is becoming evident that the next generation of therapies must have multiple functions to combat multiple mechanisms of disease progression. Metal-chelating agents provide one such

D. Ferri died in April 2010. This work was conceived and initiated by Prof. D. Ferri. & C. Manfredi [email protected] 1

Department of Chemical Sciences, University of Naples Federico II, Via Cintia, 80126 Naples, Italy

2

Dipartimento di Chimica e Biologia, Universita` di Salerno, Via Ponte don Melillo, 84084 Salerno, Italy

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function as an intervention for ameliorating metal-associated damage in degenerative diseases. Targeting chelators to adjust localized metal imbalances in the brain, however, presents significant challenges. From this perspective, we focus our attention on nicotine of which several uses have been made in various fields of applied sciences (pharmacology, medicine and biology). Some of its effects on the human body are well known since its discovery: changes in respiration, heart rate, blood pressure, constriction of arteries and increased alertness [4]. Nowadays, it is evident that they are not the only ones. In fact, there is more awareness than in the past toward the use of nicotine in numerous biological processes such as apoptosis, cell proliferation and oxidative stress [5, 6]. Some researchers suggested, for example, the possibility that nicotine binds the Fe2þ ion, inhibiting the Fenton reaction [7]. This could be the first step to explaining a lower incidence of Parkinson disease, a disease caused by an accentuated oxidative stress, in the smoking population [8]. On the other hand, the process of lipid peroxidation, related, as is known, to the generation of free radicals and to the pathogenesis of atherosclerosis [9], is more frequent in smokers than in non-smokers [10]. These apparently contradictory effects may be explained by the result that nicotine induces oxidative stress at higher concentrations than those that induce its inhibition. Our interest is to highlight some of the mechanisms by which nicotine can be involved in the presence of metal ions. As suggested by its structure, it can behave as a good ligand. This property, so far, has been exploited for the extraction of nicotine from tobacco leaves [11]. The recent discovery that the role of nicotine as ligand can be recognized in many biological processes, outlines a new research field oriented to the use of nicotine complexes with metal ions for therapeutic uses. It was, for example, demonstrated that nicotine is able to attenuate the dangerous effects of exposure to toxic metals and that nicotinerhodium complexes possess an anti-tumor effect similar to the well known effect of complexes of this metal with other hetero-cyclic ligands [12, 13]. In this work we report an accurate chemical investigation of thermodynamic data which can contribute to clarifying the interactions of nicotine with various metals of biological interest. A first attempt to understand the interactions between nicotine and Pb2þ , Cu2þ , and Fe2þ was carried out. The choice of lead, which is a toxic heavy metal, was determined by the capacity of the nicotine to decrease the level of poisoning induced by this ion (please observe the paper ‘‘Nicotine attenuates spatial learning deficits induced in the rat by perinatal lead exposure’’ by Mingfu Zhou and Janusz B. Suszkiw) [14].

2 Experimental 2.1 Reagents and Analysis Pb(ClO4 )2 stock solutions were prepared by addiction of HClO4 (Fluka ACS Reagent Grade 60 % w/w) to (PbCO3 )Pb(OH)2 (Carlo Erba RPE), until a pH ’ 3. The Pb2þ ion concentration in stock solutions was determined by a coulometric titration. Mercury, zinc, lead and copper metals were Sigma–Aldrich Chemical Co. products. Constant current coulometry has been used to prepare perchlorate solutions containing Cu2þ ions. Fe3þ ion concentrations in stock solutions were determined by atomic absorption spectroscopy. FeCl2 solutions were prepared in situ by reducing Fe3þ (NH4 Fe(SO4 )2 salt, 98–101 % purity, GR grade, BDH Chemicals Ltd.) with H2 (g). NaClO4 stock solutions were synthesized from HClO4 (Baker ACS Reagent Grade 60–62 % w/w) and Na2 CO3 (Fluka puriss.p.a.) [15]. They were analyzed by drying at 120 C NaClO4 and weighing the dry

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sample until the mass was costant. NaCl solutions were prepared by simply dissolving the Carlo Erba RPE product in water. The acid content was determined by a potentiometric, coulometric titration. Nicotine stock solutions were prepared from the ()nicotine (M.W. 162.23, d20°C = 1.010 gcm3 ) furnished by Toronto Research Chemicals. N2 (g) (99.999 % by S.O.N.) and H2 (g) (99.999 % by S.O.N.) were preconditioned at the proper vapor pressure, by bubbling it through a series of washing bottles containing a Cr(II) reducing solution (which performs as a very efficient oxygen trap) consisting of an acidic (HCl) solution of K2 Cr2 O7 and heterogeneous Zn amalgam, 10 % w/w solution of NaOH, in order to neutralize possible traces of HCl released by the first washing bottle and ionic medium (the same ionic medium as the test solution). N2 (g) was passed through all the test solutions.

2.2 Equipment Measurements were carried out in an air thermostat, developed in our laboratory. The temperature was kept at (25.00 0.02) C and measured by using a Pt100 TERSID thermocouple. Experimental data were collected by means of an automatic data acquisition system based on Hewlett–Packard (HP) instrumentation. Coulometric variations of the solution composition have been carried out using a HP DC Power Supply. The current intensity was accurately determined by reading the potential drop at the ends of a calibrated resistance coil, connected in series to the coulometric device. The Ag/AgCl electrodes were prepared according to Brown [16] by cathodically reducing Agþ on a Pt wire (i = 0.3 mA; t = 6 h) and then producing AgCl by oxidation of Ag (i = 0.3 mA ; t = 30 min) in a HCl 0.01 moldm3 solution. The Pt, Hg/Hg2 Cl2 reference electrodes was used in NaCl ionic medium. The glass membrane electrodes, and 640 Multi Dosimat automatic burettes, were supplied by Metrohm. Highly precise (0.02 mV) emf measurements were made by adapting the impedance of the glass electrode through operational amplifiers. The Pb(Hg) amalgam electrode comprised a platinum wire (of length 1 cm) dipped in homogeneous Pb(Hg) amalgam (1% w/w) pools on the bottom of the measuring vessel. Absorption spectra were recorded with a Varian Cary 50 UV/Vis spectrophotometer.

3 Methods and Results In all the crucial phases of this investigation rigorous applications of the principles of the equilibrium analysis were adopted. The study of the ternary system Me(II)/H2 O/nicotine is complicated by the great number of reactions that take place simultaneously. As will be clear, complexes between the metal ion and nicotine and the protolytic species of metal and of the nicotine will have to be considered. On this basis, the work was carried out in three phases: the first was the determination of the protolytic constants of the nicotine; the second, the study of the binary system Me(II)/H2 O and the third, the study of the ternary system Me(II)/H2 O/nicotine. The study was performed by measuring the emf of the cell (I): G:E:=TS=R:E:

ðIÞ

in which G.E. indicates a glass membrane electrode reversible to protons; R.E. is an external reference electrode, connected to TS through a salt bridge; TS = test solution, having various compositions as given in the following. The first stage, which consists in

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determining the cell constant, *Eg, is common to all the systems studied. A coulometric potentiometric titration was carried out as follows: a weighed volume V0 (50.00 0.05 cm3 ) of a solution TS0 = 3.000 moldm3 NaClO4 was introduced into the measuring vessel. The hydrogen ion concentration, [Hþ ], was coulometrically varied by means of the circuit (II): ðIIÞ

ðþÞPt=TS0 =A:E:ðÞ bconstant current sourcec

where A.E. 3.000 moldm3 NaClO4 /HgO(s)/Hg(l)(Pt) is an external auxiliary electrode, connected to TS0 through a salt bridge and Pt denotes a platinum anode for the oxidation of water according to the reaction: 2H2 O 4Hþ þ 4e þ O2 ðgÞ

ð1Þ

In order to estimate the amount of electrolysis produced by circuit (II), according to reaction (1), after each delivery of current of intensity i(A) for a time t (s), the emf of cell (I) was measured until it became constant. The Nernst potential of cell (I), E (mV), can be written as in Eq. 2: Eg ¼ Eg þ 59:16 log10 h þ Ej

ð2Þ

where *Eg is the glass electrode constant, h represents the equilibrium concentration of protons, instead of its activity, owing to the constancy of the activity coefficients in the presence of large concentrations of the medium ions. Ej [17] is the liquid junction potential due to the replacement of Naþ with Hþ , that can be calculated by means of Eq. 3, in 3 moldm3 NaClO4 : Ej ¼ 16:8 h

ð3Þ

It is obvious that for acidities, h, lower than 103 moldm3 , Ej can be neglected. Similarly, the term accounting for the activity factor changes can be also neglected, because the composition of TS does not differ appreciably from that of the ionic medium. According to Faraday’s law, the number of micromoles of Hþ ions produced is numerically equal to the microfaradays generated by the circuit (II), as written in the Eq. 4: lF ¼ ði tÞ=0:096487

ð4Þ

þ

In the course of the titration the concentration of free H ions in the solution coincides with H, the analytical excess of Hþ ions, and is given by the relationship: h ¼ H ¼ ðn0 þ lFÞ=ðV 0 1000Þ

ð5Þ

In Eq. 5, n0 represents the initial number of micromoles of protons in the volume, V0, of TS0. Introducing Eq. 5 into Eq. 2 we obtain Eq. 6, Eg ¼ Eg þ 59:16 log10 ðn0 þ lFÞ=ð1000 V 0 Þ

ð6Þ

which can be conveniently recast in the form of a linear function, i.e., a Gran plot [18], yielding Eq. 7 Y ¼ 1000 V 0 10Eg=59:16 ¼ 10Eg=59:16 ðn0 þ lFÞ which provides the value of n0, as well as *Eg, necessary in the next steps.

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ð7Þ


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3.1 On the Hydrolysis of Nicotine The method consists of potentiometric and spectrophotometric titrations. The pH range was 3 pH 10. By adding a weighed volume V of a solution TS1 : L moldm3 Nic, 3.000 moldm3 Naþ , 3.000 moldm3 ClO 4 to the volume V0 of the solution TS0 (3.000 moldm3 NaClO4 ), a solution TS2 : L moldm3 Nic, -H1 moldm3 Hþ , (3.000 ? H1 L) moldm3 Naþ , 3.000 moldm3 ClO 4 is obtained. Due to the basic properties of the nicotine, the pH measured for this solution varied from 8 to 10. A few titrations were performed by stepwise additions, by means of an automatic burette issuing volumes V t of a solution T: H moldm3 Hþ , (3.000 - H) moldm3 Naþ , 3.000 moldm3 ClO 4 . Other titrations were performed coulometrically, by generating or removing Hþ , according to the polarity of the circuit (II). This way reversibility was ensured throughout the pH range investigated. A similar study was performed also in 0.5, 1 and 2 moldm3 NaClO4 and 3 moldm3 NaCl. The sets of experimental data (Eg, Vt) or (Eg, lF), obtained for different analytical values of nicotine, where 1 103 moldm3 L 1 102 moldm3 , were analyzed by the computerized program LETAGROP-ETITR [19] and by graphical methods [20]. In particular, the sets of experimental data (Eg, lF) have been recalculated as the formation function Z (-log10 h) (Fig. 1), defined as the average number of ligands for each coordinating species. Z¼

ðh HÞ K 1 h1 þ 2K 1 K 2 h2 ¼ L 1 þ K 1 h1 þ K 1 K 2 h2

ð8Þ

UV/Vis spectra (absorption) at different pH values were also recorded in 0.5, 1 and 3 moldm3 NaClO4 and 3 moldm3 NaCl, as ionic medium. The experiments were performed as acid/base coulometric titrations at constant total nicotine concentration where 1 105 moldm3 L 3 104 moldm3 . For each experimental point the equilibrium free proton concentration was evaluated by measuring the emf of cell (I). The absorption spectra at various pH, for L = 3 104 moldm3 in 3 moldm3 NaCl reported in

Fig. 1 Z(-log10 h) in 1, 2 and 3 moldm3 NaClO4 . The symbols indicate the experimental data collected at various values of nicotine. The full curves have been calculated from the constant values determined in this work and reported in Table 1

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Table 1 Survey of the hydrolysis constants of nicotine obtained in the present work. The results are also given in molal (m) units Ionic medium

I (molarity)

I (molality)

-log10 K1 (molarity)

-log10 K1 (molality)

NaClO4

0.500

0.513

3.68 ± 0.02

3.67 ± 0.02

NaClO4

0.998

1.051

4.10 ± 0.03

4.08 ± 0.03

NaClO4

1.959

2.167

4.43 ± 0.03

4.39 ± 0.03

NaClO4

3.000

3.503

4.80 ± 0.02

4.73 ± 0.02

NaCl

3.000

3.200

4.31 ± 0.02

4.24 ± 0.02

Ionic medium

I (molarity)

I (molality)

-log10 K2 (molarity)

-log10 K2 (molality)

NaClO4

0.500

0.513

8.44 ± 0.09

8.43 ± 0.09

NaClO4

0.998

1.051

8.55 ± 0.05

8.53 ± 0.05

NaClO4

1.959

2.167

9.10 ± 0.09

9.05 ± 0.09

NaClO4

3.000

3.503

9.62 ± 0.05

9.56 ± 0.05

NaCl

3.000

3.200

9.23 ± 0.02

9.07 ± 0.02

The uncertainties, following the hydrolysis constants, are 3r

Fig. 2a, b, show a remarkable dependence on the pH. In particular, the wavelengths of interest are those that correspond to the absorption maxima that are sensitive to pH changes: 255, 259, 260, 261 and 266 nm. An isosbestic point (I.P.) at 242 nm can also be observed. The experimental data (symbols) Ak/pH at constant values of L are plotted in Fig. 2c. The full curves were obtained by combining mass balance with respective hydrolytic constants and the Bouger/Lambert/Beer law equation: X ei lci ¼ l ek1 ½H2 Nic2þ þ ek2 ½HNicþ þ ek3 ½Nic

Ak ¼ ð9Þ 1 ¼ lL e1 þ e2 K 1 h1 þ e3 K 1 K 2 h2 1 þ K 1 h1 þ K 1 K 2 h2 The primary data ApH/k was numerically interpreted by the computerized Hyperquad program [21]. The potentiometric and spectrophotometric collected data can be explained by two hydrolytic reactions show in the scheme: H2 Nic2þ HNicþ þ Hþ

ð10Þ

HNicþ Nic þ Hþ

ð11Þ

The conditional protolysis costants of the nicotine determined in the present work are reported in Table 1. By applying the SIT to the formation constants expressed in molal units, the following equations are obtained:

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þ 0 v1 ¼ log10 K m 1 þ 2D þ eðH ; ClO4 Þ ¼ log10 K 1 DðeÞ m

ð12Þ

þ 0 v2 ¼ log10 K m 2 þ 2D þ eðH ; ClO4 Þ ¼ log10 K 2 DðeÞ m

ð13Þ

þ DðeÞ1 ¼ eðH2 Nic2þ ; ClO 4 Þ eðHNic ; ClO4 Þ

ð14Þ

DðeÞ2 ¼ eðHNicþ ; ClO 4 Þ eðNic; NaClO4 Þ

ð15Þ


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Fig. 2 Absorption spectra of nicotine in 3 moldm3 NaCl at 3 pH 10, for L = 3 104 moldm3

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If we plot the first members of equations versus m, the molal concentration of ClO 4 , we obtain log10 K10 and log10 K20 , hydrolysis constants at zero ionic strength, and DðeÞ1 , DðeÞ2 values: log10 K 01 ¼ 3:3 0:2 log10 K 02 ¼ 7:7 0:3 DðeÞ1 ¼ 0:23 0:05 kg mol1 DðeÞ2 ¼ 0:38 0:05 kg mol1 The distribution diagrams of nicotine in 0.5, and 3 moldm3 NaClO4 , as example, are reported in Fig. 3a, b.

Fig. 3 Distribution diagrams of nicotine in 0.5 (a), and 3 moldm3 (b) NaClO4

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3.2 On the Ternary Pb(II)–Nicotine–Water System Complex formation between lead(II) and nicotine have been investigated in 3 moldm3 NaClO4 by measuring the potential of cell (I) and Pb2þ /Pb(Hg) amalgam electrodes of cell (III) PbðHgÞ=TS=R:E:

ðIIIÞ

2?

Pb(Hg) is a Pb /Pb(Hg) amalgam electrode constituted by a platinum wire (of length 1 cm) dipped in Pb(Hg) amalgam (1 % w/w) pools on the bottom of the measuring vessel. E(III) can be written as in Eq. 16: EðIIIÞ ¼ E0Pb2þ =PbðHgÞ þ 29:58 log10 ½Pb2þ 29:58 log10 fPbðHgÞg þ 29:58 log10 cPb2þ þ Ej ð16Þ where E0Pb2þ =PbðHgÞ is the amalgam electrode constant, including the RE constant. The first step consists in determining the amalgam electrode constant, by a coulometric potentiometric titration: a weighed volume V 0 (50.00 0.05 cm3 ) of a solution TS0 = 3.000 moldm3 NaClO4 was introduced into the measuring vessel. The analytical concentration of Pb2þ ion, B , was varied by means of the coulometric cell (IV) ðþÞPbðHgÞ=TS=A:E:ðÞ bconstant current sourcec

ðIVÞ

After each delivery of current of intensity i(A) for a time t (s), the emf E(III) (mV) was measured until constancy. E0Pb2þ =PbðHgÞ and the initial micromoles of Pb2þ are determined by the Gran method. In the resulting solution TS of composition 3.000 moldm3 NaClO4 , B moldm3 Pb2þ , the second step takes place by stepwise addition of equal volumes of 3 solutions ST1 = (3.000 ? H) moldm3 Naþ , 3.000 moldm3 ClO OH 4 , H moldm 3 þ 3 3 2þ and ST2 = (3.000 2B ) moldm Na , 3.000 moldm ClO4 , 2B moldm Pb to avoid the hydrolysis of Pb2þ ion. After each addition the emf E(III) (mV) was measured until it remained constant to within 0.02 mV, for at least 15 minutes. The primary data E(III)/(V) and Eg(V) have been graphically and numerically interpreted with the computerized least-squares program LETAGROP-ETITR by minimizing the functions: X ðEPb2þ =PbðHgÞðcalcÞ EPb2þ =PbðHgÞðexpÞ Þ2 ð17Þ UE ¼ and UB ¼

X

ðBðcalcÞ BðexpÞ Þ2

ð18Þ

Results obtained are in a good agreement with literature data [22, 23] for all the hydrolytic species. The interpretation of data indicated also the new species Pb2 (OH)2þ 2 that was not rejected by recalculating data reported in the cited article. The presence of this hydroxocomplex is not a surprise. As suggested elsewhere [24], in fact, the formation of the dimer seems not to be a property of the metal ion, but a property of hydroxide ion. The dimerization constant related to the reaction is always the same within the experimental error for different metal ions. In Fig. 4 we report the distribution diagram of a solution

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Fig. 4 Distribution diagrams of Pb(II) 2 103 moldm3 in 3 moldm3 NaClO4 using the formation constants obtained from this work

2 103 moldm3 Pb2þ , constructed by using the formation constants obtained from this work. The third step consists of the determination of the stoichiometry and formation constants of Pb(II)/nicotine complexes. The study has been conducted by volumetric–potentiometric titrations using two different procedures with the aim to simplify the elaboration of the experimentally collected data. The experimental conditions have been varied within the following intervals: 1 9 103 moldm3 B 1 101 moldm3 , 1 103 moldm3 L 1 101 moldm3 . A weighed volume V cm3 of a S1 stock solution of nicotine (S1 = L moldm3 nicotine, 3.000 moldm3 NaClO4 ) was added to the solution TS2 : H’ moldm3 Hþ , B moldm3 Pb2þ , (3.000 - H - 2B) moldm3 Naþ , 3.000 3 moldm3 ClO Hþ , B 4 . The composition of the resulting solution is TS3 : H moldm 3 2þ 3 3 þ moldm Pb , L’ moldm nicotine, (3.000 H 2B) moldm Na , 3.000 moldm3 ClO 4. An increase of pH is the consequence of the addition of the basic nicotine solution. This effect promotes the formation of hydrolytic species of Pb2þ .

3.2.1 Procedure 1: Volumetric Titration with Variation of B and L This procedure takes place by stepwise additions of V cm3 of TS1 = H moldm3 Hþ , (3.000 H) moldm3 Naþ , 3.000 moldm3 ClO 4 to the solution TS3 . After each addition of TS1 to TS3 the emfs of the cells (I) and (III) were measured until they remained constant to within 0.02 mV for at least 15 minutes.

3.2.2 Procedure 2: Volumetric Titration with Constant B and L Measured volumes V1 and V2 = 2V1, respectively, of two solutions ST1 = H moldm3 Hþ , 3 (3.000 H) moldm3 Naþ , 3.000 moldm3 ClO Pb2þ , 4 and ST2 = B moldm

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L moldm3 Nic, (3.000 2B) moldm3 Naþ , 3.000 moldm3 ClO 4 were added to a solution of nicotine L/3 moldm3 . The primary data E(III)/(V) and Eg(V) have been graphically and numerically analyzed with the computerized least-squares program LETAGROP-ETITR. The measurements have been interpreted by assuming the formation of mononuclear complexes only, according to the reactions: þ Pb2þ þ 2H2 Nic2þ þ 2H2 O PbðHNicÞ4þ 2 þ 2H3 O þ Pb2þ þ 4H2 Nic2þ þ 4H2 O PbðNicÞ2þ 4 þ 8H3 O

In Fig. 5 we report the distribution diagrams for various L/B ratio, constructed using the equilibrium constants of Table 2.

3.3 On the Fe(II)–Nicotine–Water System Complex formation between Fe(II) and nicotine was investigated in 3 moldm3 NaClO4 and 3 moldm3 NaCl as ionic medium by potentiometric measurements of a glass electrodes, sensitive to Hþ ions (cell (I)). The pH investigated was 3 pH 7, while 1 103 moldm3 B 5 103 moldm3 . The lower limit of acidity is imposed by precipitation of sparingly soluble Fe2þ oxide. As reported in the literature [25], ferrous ions hydrolyze to produce mononuclear species FeOHþ and Fe(OH)2 4 between pH = 7 and 14, but their stabilities are known with less precision than is generally possible. Polynuclear species of ferrous ions, which may exist at high concentrations of Fe(II), have not been reported. A typical experiment conducted in 3 moldm3 NaClO4 consists of three steps: Step 1 Determination of *Eg, the glass electrode constant by a coulometric titration in the ionic medium. Step 2 Preparation, in situ, of the Fe(II) test solution, TS1 : an accurately weighed quantity of Fe(III) salt (NH4 Fe(SO4 )2 furnished by BDH Chemicals) was added to the solution resulting at the end of the previous step; thus solution TS1 = B moldm3 Fe3þ , H moldm3 Hþ , was obtained. N2 (g) was replaced by ultra pure H2 (g) in the presence of a Pd sponge for about 24 h, to obtain the complete reduction of Fe3þ to Fe2þ according to the reaction: Fe3þ þ 1=2H2 ðgÞ Fe2þ þ Hþ When the reduction of Fe(III) to Fe(II) is complete, the composition of the solution in the titration vessel is TS2 = B moldm3 Fe2þ , H 1 moldm3 Hþ , (3.000 H1 2B) moldm3 Naþ , 3.000 moldm3 ClO 4. Step 3 A weighed volume of nicotine in 3.000 moldm3 NaClO4 was added to the solution TS2, resulting from the previous step. TS3 = B moldm3 Fe2þ , H moldm3 Hþ , (3.000 H 2B) moldm3 Naþ , L moldm3 nicotine, 3.000 moldm3 ClO 4 was obtained. The analytical concentration of Hþ ions, H, was stepwise decreased through the circuit (II).

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Fig. 5 Distribution diagrams of the Pb2þ /nicotine system in 3 moldm3 NaClO4 at various L /B ratios

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Table 2 Survey of the equilibrium constants, valid in 3 moldm3 NaClO4 Reaction

-log10 K

H2 Nic2þ ? H2 O HNicþ ? H3 Oþ

4.63 ± 0.02

HNicþ ? H2 O Nic ? H3 Oþ

9.41 ± 0.01

Pb2þ ? H2 O Pb(OH)þ ? H3 Oþ 2þ

2Pb

? 2H2 O

4Pb2þ ? 4H2 O

3Pb2þ ? 4H2 O

2þ

6Pb

? 8H2 O

7.8 ± 0.2

þ Pb2 ðOHÞ2þ 2 ? 2H3 O 4þ þ Pb4 ðOHÞ4 ? 4H3 O þ Pb3 ðOHÞ2þ 4 ? 4H3 O

19.21 ± 0.01

Pb6 ðOHÞ4þ 8

41.98 ± 0.07

12.2 ± 0.1

22.43 ± 0.04

þ

? 8H3 O

þ Pb2þ ? 2H2 Nic2þ ? 2H2 O PbðHNicÞ4þ 2 ? 2H3 O 2þ

Pb

2þ

? 4H2 Nic

? 4H2 O

PbðHNicÞ2þ 4

? 8H3 O

8.04 ± 0.03

þ

42.0 ± 0.1

The uncertainties, following the hydrolysis constants, are 3r

ðÞPt=TS3 =A:E:ðþÞ

ðIIÞ

bconstant current sourcec After each delivery of current of constant intensity, i (A), for a time t (s), the emf, Eg, of cell (I) was measured untill constancy: G:E:=TS3 =R:E:

ðIÞ

ð19Þ

The solution acidity decreased, while the molar ratio L/B was kept constant. Volumetric titration with variation of B and L have also been conducted: the solution resulting from the step 2) was titrated by adding known volumes of a solution TS4 = L moldm3 nicotine, 3.000 moldm3 Naþ , 3.000 moldm3 ClO 4 . The molar ratio L/B varied in the range 1 L/B 20. The primary data Eg(V) or Eg(lF) have been numerically analyzed by the computerized least-squares program LETAGROP-ETITR. The experimental data can be explained assuming the formation of two mononuclear complexes with the conditional formation constants reported in Tables 3 and 4:

Table 3 Survey of the equilibrium constants, valid in 3 moldm3 NaClO4 , obtained in the present work Reaction

log10 K


4.42 ± 0.03


9.38 ± 0.05

Fe2þ ? H2 Nic2þ ? H2 O Fe(HNic)3þ ?H3 O?

3.06 ± 0.06

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Table 4 Survey of the equilibrium constants, valid in 3 moldm3 NaCl, obtained in the present work Reaction

log10 K


4.21 ± 0.03


8.95 ± 0.05

Fe2þ ? H2 Nic2þ ? H2 O Fe(HNic)3þ ? H3 Oþ

2.25 ± 0.09

þ Fe2þ ? 4H2 Nic2þ ? 4H2 O Fe(HNic)6þ 4 ? 4H3 O

9.44 ± 0.08

Fe2þ þ H2 Nic2þ þ H2 O FeðHNicÞ3þ þ H3 Oþ þ Fe2þ þ 4H2 Nic2þ þ 4H2 O FeðHNicÞ6þ 4 þ 4H3 O

In Figs. 6 and 7 we report the distribution diagrams for various L/B ratios, in 3 moldm3 NaCl and 3 moldm3 NaClO4 as ionic medium, constructed using the equilibrium constants of Tables 3 and 4.

3.4 On the Cu(II)–Nicotine–Water System The investigation was inspired by the pharmacological studies [26, 27] that underline the beneficial effect of nicotine against Alzheimer’s desease (AD), showing how nicotine attenuates b-amiloid induced neurotoxicity by regulating copper homeostasis in AD brains. The study has been conducted at (25.00 0.02) C, in 0.5 moldm3 NaClO4 as ionic medium by measuring the emf of the cell (I): G:E:=TS=R:E:

ðIÞ

The experimental method consists of coulometric titrations consisting in three steps:

Fig. 6 Distribution diagram of the Fe2þ /nicotine system B = 2 103 moldm3 , valid in 3 moldm3 NaClO4

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Fig. 7 Distribution diagram of the Fe2þ /nicotine system, B = 2 103 moldm3 , valid in 3 moldm3 NaCl

Step 1 Determination of *Eg, the glass electrode constant and H0, the initial analytical excess of protons Hþ , by a potentiometric–coulometric titration measuring the emf of cell(I). Step 2 Preparation, in situ, of the Cu(II) TS2 test solution. By adding a weighed volume V1 of a stock solution of nicotine L moldm3 was obtained TS1 = L moldm3 Nic, 0.500 2þ moldm3 Naþ , 0.500 moldm3 ClO ion, B 4 . The analytical concentration of Cu 3 moldm , was varied by means of the coulometric cell (IV): ðþÞCuðsÞ=TS1 =A:E:ðÞ

ðIVÞ

bconstant current sourcec Step 3 The analytical concentration of Hþ ions, H, was stepwise decreased, through the circuit (II):

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Table 5 Survey of the equilibrium constants, valid in 0.5 moldm3 NaClO4 , obtained in the present work Reaction

log10 K

Cu2þ ? H2 Nic2þ ? H2 O Cu(HNic)3þ ? H3 Oþ

1.55 ± 0.03

Fig. 8 Distribution diagram of Cu2þ /nicotine system, B = 1 103 moldm3 , valid in 0.5 moldm3 NaClO4

ðÞPt=TS2 =A:E:ðþÞ

ðIIÞ

bconstant current sourcec where TS2 = B moldm3 Cu2þ , L moldm3 Nic, 0.500 moldm3 Naþ , 0.500 moldm3 ClO 4 . After each delivery of costant current intensity, i(A), for a time t (s), the emf of cell

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(I) was measured untill constancy. The pH investigated was 3 pH 6, while 1 103 moldm3 L 9 103 moldm3 and molar ratio L/B varied 1 L / B 7. The lower limit of acidity is imposed by precipitation of sparingly soluble oxide of Cu2þ . The primary data have been numerically analyzed with the computerized least-squares program LETAGROP-ETITR. The experimental data can be explained assuming the formation of one mononuclear species with the conditional formation constant reported in Table 5. In Fig. 8, we report the distribution diagrams of Cu2þ /nicotine system in 0.5 moldm3 NaClO4 for two L/B ratio, constructed using the equilibrium constants determined in this work.

4 Conclusions The hydrolysis constants of nicotine have been determined in NaClO4 ionic medium and recalculated on the thermodynamic scale (infinite dilution) by using the SIT. The formation of Me(II)/nicotine mononuclear complexes have been obtained.

5 List of Symbols All of the concentrations are expressed in units of moldm3 , molarity. Molality units, molðkgH2 O Þ1 are only used when applying the SIT. Nic, HNicþ , H2 Nic2þ h = [Hþ ] H L B b A l K1

Abbreviations for the protolytic species of the nicotine Free proton concentration Protons excess with respect to the zero level represented by ionic medium Analytical concentration of nicotine Analytical concentration of metal(II) Concentration of free metal ion Absorbance Optical path [HNicþ ][Hþ ][H2 Nic2þ ]-1: equilibrium constant of the reaction (20), valid in the ionic medium H2 Nic2þ HNicþ þ Hþ

K2

[Nic][Hþ ][HNicþ ]1 : equilibrium constant of the reaction (21), valid in the ionic medium HNicþ Nic þ Hþ

K1K2

ð20Þ

ð21Þ

[Nic][Hþ ]2 [H2 Nic2þ ]1 : equilibrium constant of the reaction (22), valid in the ionic medium H2 Nic2þ Nic þ 2Hþ

ð22Þ

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(p, q, r) I D

J Solution Chem (2016) 45:971–989

Synthetic expression to represent the species (Pbq (OH)p Nicr )ð2qpÞ 1/2R(Ci z2i ): ionic strength Debye’s term in the Specific Interaction Theory (SIT) pffi = 0:5109pffiI ð1þ1:5 I Þ

ci ei (i, k) log10 ci ¼ z2i D þ Rei ði; kÞ mK Z

Activity coefficient of ion i in molal units Interaction coefficient between species i and k SIT equation Formation function =

ðhHÞ L

Acknowledgments The present work is part of a project financed by BAT, British American Tobacco.

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