Materials Science and Engineering C 40 (2014) 164–171
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Comparative study of adsorption capacity of mesoporous silica materials for molsidomine: Effects of functionalizing and solution pH N.A. Alyoshina, A.V. Agafonov, E.V. Parfenyuk ⁎ G.A. Krestov Institute of Solution Chemistry of Russian Academy of Sciences, 1 Akademicheskaya Str., Ivanovo, Russian Federation
a r t i c l e
i n f o
Article history: Received 29 October 2013 Received in revised form 11 February 2014 Accepted 21 March 2014 Available online 30 March 2014 Keywords: Mesoporous silica Surface functional groups Molsidomine Solution pH Adsorption interactions
a b s t r a c t Adsorption capacities of mesoporous silica materials having various surface functional groups (hydroxyl, phenyl, mercaptopropyl, aminopropyl) at pH values of 4.8, 7.4, and 8.0 were studied. It was found that the maximum amount of adsorbed molsidomine is affected by method of preparation of the silica materials, chemistry of their surfaces and solution pH from where adsorption is carried out. The effects were explained by different states of the adsorbents and molsidomine in solution at the studied pH. The most efficient adsorption of molsidomine is observed onto phenyl modified silica prepared by grafting at pH 4.8. Aminopropyl modified silica adsorbs the lowest amount of molsidomine and the adsorption was observed only at pH 7.4. Interactions responsible for the adsorption were elucidated by spectroscopic studies. © 2014 Elsevier B.V. All rights reserved.
1. Introduction Studies of drug adsorption on porous silica materials can be of interest for the development of new technologies of waster treatment, purification of drugs and separation of their mixtures, quantitative determination of drugs in blood plasma, creation of new drug formulations with improved therapeutic and consumer properties, etc. Adsorption capacity of the materials is one of the most important characteristics in such applications. Adsorption capacity depends on parameters of porous structure of adsorbents (pore size and volume, specific area). It is clear, for example, that very small pore diameter (with respect to drug molecule size) does not promote high adsorption [1,2]. According to numerous studies, adsorption capacity of porous silica materials can be improved significantly by functionalizing their surfaces with judiciously chosen organic groups [3–7]. The functionalizing promotes surface–drug interactions and therefore, leads to improved adsorption capacity of the materials for drug molecules. The results show that the higher the concentration of functional groups, the better adsorption of drug is observed [3,6]. However in some cases the type of functional groups and not their density in the materials is mainly responsible for the differences in adsorption capacity of materials [5]. Another factor affecting adsorption capacity is properties of medium from what adsorption occurs. The pH value of a solution is one of the most important parameters affecting the adsorption process [7–9]. In fact, solution pH affects both surface binding sites of the adsorbent ⁎ Corresponding author. E-mail address: [email protected] (E.V. Parfenyuk).
http://dx.doi.org/10.1016/j.msec.2014.03.052 0928-4931/© 2014 Elsevier B.V. All rights reserved.
and state of drug molecules in solution. A change in pH may result in a change in charge profile of adsorbent species, which has effects on the interactions between adsorbate species and adsorbent. Depending on the nature of surface functional groups, adsorbent may be neutral (pH = pHpzc, at point of zero charge), positively (pH b pHpzc) or negatively (pH N pHpzc) charged due to protonation or dissociation of the functional groups. On other hand, because drugs are often weak electrolytes, they have ionizable functional groups that depend on pH values. Therefore, pH value is one of the most important factors controlling adsorption interactions and hence, adsorption capacity. This is confirmed by the results of experimental studies. For example, the adsorption capacities of mesoporous silica materials (unfunctionalized (HMS) and mercapto-(M-HMS) and amino-functionalized (A-HMS)) for diclofenac and carbamazepine are dependent on the pH, being highest at pH 5, due to the optimal electrostatic interactions and hydrogen bonding at this pH [7]. Efficiency of SBA-15 as adsorbent for series of pharmaceuticals is also dependent on pH [8]. The results of this work showed that SBA-15 is very effective adsorbent for the studied pharmaceuticals in acidic media and their adsorption is mainly controlled by hydrophilic interactions between functional groups in pharmaceutical molecules and silanol groups on silica surface, rather than a hydrophobic sorption. In this study, adsorption capacity of mesoporous silica materials with various surface functional groups (hydroxyl, mercaptopropyl, aminopropyl, phenyl) for drug molsidomine is studied at different pH values. The work is a continuation and extension of our previous studies [10–12] devoted to the development of efficient technology of the drug adsorption onto porous silica materials. Because all materials under study contain acid–base surface groups, a change in pH can affect the drug adsorption.
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2.2. Syntheses of the silica materials
Fig. 1. Molecular structure of molsidomine.
Molsidomine (N-(ethoxycarbonyl)-3-(4-morpholino)sydnonimine) is the drug used clinically for therapy of cardiovascular diseases. Chemically it belongs to the class of sydnonimines and has mesoionic nature. Structural formula of molsidomine is presented in Fig. 1. It has been found that molsidomine is stable in acid and neutral solutions. Titration of aqueous molsidomine with 1 N HCl allows the estimation of pKa that was found to be 3.34 at 298 K [13]. In extreme alkaline solutions, it decomposes to the carboxylate, ammonia, and monoethyl carbonate, which further decomposes to ethanol and carbon dioxide [13]. Due to the presence of heterocycle in its molecule, molsidomine exhibits aromatic properties. On the other hand, as mesoionic compound, molsidomine is highly polar and should favor strong hydrophilic interactions (for example, electrostatic, ion-dipole, hydrogen bonding) which will be affected by pH. It is impossible to establish a priori what interactions will be responsible for efficient molsidomine adsorption. Therefore, the aim of the present work is three-fold: to compare the adsorption capacities of the synthesized silica materials for molsidomine at different pH values, to elucidate the interactions responsible for the adsorption and to choose the most efficient adsorbent and favorable condition for the adsorption.
Unmodified silica (UMS) was synthesized by acid catalyzed hydrolysis and base catalyzed polycondensation of TEOS in the presence of D-glucose as structure-forming agent as described in [14]. The template as 50 wt.% D-glucose solution (4.2 g of D-glucose in 4.2 g of distilled water) was added after neutralization of the prehydrolyzed TEOS sol. The procedure of one-pot synthesis of phenyl-modified silica (PhMS-c) was similar to that described above. The phenyl functionality is introduced into the silica framework by the simultaneous addition of TEOS and PhTMOS in a molar ratio of 0.95:0.05 [15]. The as-synthesized samples were washed by hot water and centrifuged triply to remove D-glucose and then dried at in an oven at 120 °C overnight. FTIR spectra showed that the removal of glucose was complete. Mercaptopropyl and aminopropyl functionalized silica materials (MMS and AMS) were prepared by grafting. Phenyl modified silica material (PhMS-g) was also prepared by grafting. The modifier (MTMOS, APTES, PhTMOS; 1.5 ml) was added to an ethanolic suspension of UMS particles (5 g in 150 mL). The suspension was stirred at room temperature for 20 h. The sample was finally centrifuged and washed two times in ethanol. 2.2.1. Adsorption experiments Typically, 0.3 g of the synthesized mesoporous silica and 67 mL of molsidomine solution in buffer were mixed and stirred for 5 h in a temperature-controlled cell (T = 298 K) and after centrifugation for 15 min at 10 000 rpm the supernatant was analyzed with UV–Vis absorption spectrometer Agilent 8453 by monitoring the major peak at 310 nm, which corresponds to the absorption maximum of molsidomine. The initial concentration of molsidomine was changed from 0.016 · 10−3 to 0.158 · 10−3 mmol·ml−1. The surface concentrations of the adsorbed molsidomine were calculated according to the equation qe ¼
ðС 0 −C s Þ V ; m
ð1Þ
where qe is the surface molsidomine concentration (mmol·g−1), C0 and Cs are the bulk molsidomine concentrations before and after adsorption (mmol·ml−1), V is a volume (ml), and m is a mass of the adsorbent sample (g). The estimated relative error in qe is found to be 3%.
2. Experimental 2.1. Materials Tetraethoxysilane (TEOS) (high purity grade, Russia), 3aminopropyltriethoxysilane (APTES) (Aldrich, 99%), phenyltrimethoxysilane (PhTMOS) (Acros, 85%), mercaptopropyl trimethoxysilane (MTMOS) (Aldrich, 95%), D-glucose (ICN Biomedicals, N99% purity), and molsidomine (N-(ethoxycarbonyl)-3-(4-morpholino)sydnonimine) (Aldrich) were used without further purification. Sodium hydrogen phosphate and sodium dihydrogen phosphate (Russia, analytical grade) were used to prepare buffer solutions (pH 4.8, 7.4, 8.0) on the basis of doubly distilled deionized water. Sodium chloride (ChemMed, purity grade, Russia) and potassium bromide (Acros, 99+%, IR grade) were dried at 250 °C before use.
2.2.2. FTIR spectroscopy FTIR spectra of crystal molsidomine, the synthesized silica materials and their composites with the drug were recorded using an Avatar 360 FT-IR ESP spectrometer at room temperature. The spectra were recorded in the range of 4000 to 400 cm−1. The samples were examined as KBr disks. 2.2.3. Acid–base titration of molsidomine solution Acid–base properties of molsidomine were investigated by potentiometric titration method. Molsidomine solution (0.01 M) was divided into two portions. One of them was titrated by 0.01 M solution of KOH
Table 1 Parameters of porous structure and concentrations of surface groups of silica materials [10–12]. Samples
Specific surface area, m2/g
Total pore volumea, cm3/g
Average pore sizeb, nm
Concentration of incorporated organic surface groups mmol/g
UMS PhMS-c PhMS-g AMS MMS a b c
694 640 626 403 563
0.53 0.57 0.50 0.32 0.48
2.8 3.1 2.7 2.6 2.6
The single point pore volume determined at P/P0 = 1. Pore diameter according to the maximum of the BJH pore size distribution calculated from the desorption branch of the isotherm. Concentration of surface silanol groups.
c
6.62 0.54 0.47 1.40 0.14
mmol/m2 9.5 8.5 7.5 3.5 2.5
· · · · ·
10−3c 10−4 10−4 10−3 10−4
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Table 2 Isotherm models and their parameters of the synthesized silica materials for molsidomine adsorption at different pH values at 298 K. Model
Parameters
UMS
PhMS-c
PhMS-g
MMS
AMS
pH 4.8 max K L C e Langmuir qe ¼ q1þK L Ce
Freundlich qe = KF ⋅ C1/n e 1=n
e Sips qe ¼ qmax K S C1=n
1þK S C e
Redlich–Peterson qe ¼
K R−P C e 1þα R−P C βe
max K L C e Langmuir qe ¼ q1þK L Ce
Freundlich qe = KF ⋅ C1/n e 1=n
e Sips qe ¼ qmax K S C1=n
1þK S C e
Redlich–Peterson qe ¼
K R−P C e 1þα R−P C βe
max K L C e Langmuir qe ¼ q1þK L Ce
Freundlich qe = KF ⋅ C1/n e 1=n
e Sips qe ¼ qmax K S C1=n
1þK S C e
Redlich–Peterson qe ¼
K R−P C e 1þα R−P C βe
qmax, (mmol·g−1) KL, (L·g−1) R2 KF, (mmol1 − 1/n·L1/n·g−1) 1/n R2 qmax, (mmol·g−1) Ks, (L·g−1)1/n 1/n R2 KR-P, (L·g−1) αR-P, (L·g−1)β β R2
1.47 · 10−3 0.36 · 104 0.9962 0.471 0.77 0.9824 1.26 · 10−3 0.89 · 104 1.07 0.9965 4.582 27.5 · 109 2.81 0.9667
4.21 · 10−3 0.58 · 104 0.9942 1.245 0.73 0.9372 1.56 · 10−3 129 · 105 0.63 0.9978 24.137 24 · 106 1.88 0.9844
4.65 · 10−3 0.87 · 104 0.9829 0.574 0.61 0.9483 2.65 · 10−3 75.5 · 105 0.64 0.9983 36.496 1.59 · 106 1.59 0.9907
2.22 · 10−3 0.21 · 104 0.9770 0.069 0.42 0.9082 1.64 · 10−3 564 · 105 0.59 0.9986 38.023 3.68 · 105 1.34 0.9952
–
qmax, (mmol·g−1) KL, (L·g−1) R2 KF, (mmol1 − 1/n·L1/n·g−1) 1/n R2 qmax, (mmol·g−1) Ks, (L·g−1)1/n 1/n R2 KR-P, (L·g−1) αR-P, (L·g−1)β β R2
pH 7.4 2.14 · 10−3 0.56 · 104 0.9902 0.582 0.72 0.9709 1.09 · 10−3 24.9 · 105 0.67 0.9969 11.265 59.2 · 105 1.78 0.9912
3.72 · 10−3 0.58 · 104 0.9432 0.496 0.65 0.9380 1.75 · 10−3 92.7 · 105 0.62 0.9958 19.635 15.4 · 106 1.88 0.9632
1.48 · 10−3 3.64 · 104 0.9901 0.069 0.45 0.9149 1.29 · 10−3 6.20 · 105 0.81 0.9979 48.820 0.94 · 105 1.11 0.9806
1.20 · 10−3 1.13 · 104 0.9726 0.111 0.54 0.9118 0.90 · 10−3 16.0 · 106 0.62 0.9974 15.017 17.5 · 105 1.57 0.9970
0.72 · 10−3 1.33 · 104 0.9834 0.048 0.52 0.9202 0.48 · 10−3 44.6 · 106 0.58 0.9945 7.373 50 · 106 1.96 0.9860
qmax, (mmol·g−1) KL, (L·g−1) R2 KF, (mmol1 − 1/n·L1/n·g−1) 1/n R2 qmax, (mmol·g−1) Ks, (L·g−1)1/n 1/n R2 KR-P, (L·g−1) αR-P, (L·g−1)β β R2
pH 8.0 1.01 · 10−3 0.66 · 104 0.9911 0.197 0.68 0.9430 0.48 · 10−3 11.2 · 106 0.62 0.9980 6.180 5.44 · 107 2.00 0.9960
1.38 · 10−3 2.26 · 104 0.9957 0.093 0.49 0.9618 1.35 · 10−3 5.0 · 104 0.93 0.9948 27.248 0.50 · 105 1.11 0.9962
1.29 · 10−3 1.15 · 104 0.8981 0.045 0.46 0.8288 0.73 · 10−3 2.13 · 1011 0.39 0.9948 10.748 3.13 · 108 2.19 0.9910
1.35 · 10−3 0.31 · 104 0.9952 0.244 0.72 0.9342 0.40 · 10−3 5.86 · 108 0.59 0.9985 3.961 3.26 · 1010 2.79 0.9664
–
–
–
–
–
–
–
and the other portion was titrated by 0.01 M solution of HCl. In all titrations, the solution was stirred for 20 min after each addition of acid or base and the pH was measured with a pH/ION Analyzer Radelkis (Budapest). 2.2.4. Determination of zero point charge (pHZPC) of the silica material The point of zero charge of AMS sample was determined by the batch equilibration method [16], using NaCl aqueous solution (0.01 M) as a background electrolyte. The NaCl solution was placed into series of vials, 50 ml per vial, which initial pH values (pHi) were adjusted by 0.01 M KOH or 0.01 M HCl. 0.1 g sample of the AMS was introduced in each vial. The suspensions were stirred for 0.5 h and the equilibrium pH value (pHe) was measured. The dependence of ΔpH = pHe − pHi on pHi allows the determination of the pHZPC value. The measurements were carried out with a pH/ION Analyzer Radelkis (Budapest). The obtained pHZPC of AMS is found to be 8.0. 3. Results and discussion In our previous work [10,11] we have showed that the synthesized silica materials are amorphous and mesoporous and have high specific area and pore volume. The concentration of surface organic groups of
Fig. 2. Comparison of different isotherm models for molsidomine adsorption on PhMS-c at pH 7.4: 1—Langmuir model; 2—Freundlich model; 3—Sips model; 4—Redlich–Peterson model.
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Fig. 3. Effect of solution pH on molsidomine adsorption onto the synthesized silica materials at 298 K: 1 — UMS, 2 — PhMS-c, 3 — PhMS-g, and 4 — MMS.
the functionalized silica materials was estimated from elemental analysis data and the concentration of hydroxyl groups of UMS was estimated by thermal analysis method [10–12]. The parameters of porous structure and concentrations of the surface groups are presented in Table 1. In order to discover the adsorption capacity of the synthesized silica materials for molsidomine, the experimental data points were fitted to the Langmuir, Freundlich, Redlich–Peterson and Sips (Langmuir– Freundlich) empirical models which are the most frequently used two- and thee-parameter equations in the literature describing the non-linear equilibrium between adsorbed drug and in solution at a constant temperature. The isotherm equations and their parameters at all studied pH values are given in Table 2. By comparing the correlation coefficients (R2) for the four models at different pH values, it can be inferred that the isotherms are more adequately fitted by the Sips model. As an example, Fig. 2 demonstrates comparison of different isotherm models for molsidomine adsorption on PhMS-c at pH 7.4.
3.1. Effect of surface chemistry on adsorption capacity of the silica materials. Interactions that are responsible for molsidomine adsorption Fig. 3 shows the qmax trend at different pH values for molsidomine adsorption on the silica materials. As can be seen from this figure, practically at all studied pH values the highest adsorption capacity is observed on phenyl modified silica materials (PhMS-g and PhMS-c). AMS exhibits the lowest adsorption capacity for molsidomine. It should be noted that no correlation is observed between the qmax value and both the parameters of porous structure and concentration of the incorporated surface groups (Fig. 4. As an example, Fig. 4(a) demonstrates the correlation between the qmax value and the total pore volume value. No correlation was observed between the qmax and the surface area. Therefore, it may be supposed that aromatic groups of the phenyl modified silica materials contribute significantly to efficient adsorption of molsidomine on these adsorbents. Because the adsorbents contain surface phenyl groups and molsidomine molecules contain electron
deficient heterocycle, π–π interaction may occur between them. This supposition was confirmed by spectral studied. As an example, Fig. 5 shows UV spectra of molsidomine and suspensions of its composites with PhMS-c in a solution at pH 7.4. As can be seen in Fig. 5, two characteristic intensive bands are presented in the molsidomine spectrum (spectrum 1). The first band at 310 nm is assigned to π → π* electronic transition due to p–π conjugation in sydnonimine ring. The second band (229 nm) results from n → π* electronic transition and can be attribute to exocyclic group [17]. In the spectrum of the composite (spectrum 2) the first band exhibits a red shift (from 310 nm to 313 nm). The red shift of π → π* electronic transition band indicates that the sydnonimine heterocycle is involved in interaction with the adsorbent surface. Analogous changes in UV spectra were observed at interaction of phenanthrene with humic subunits [18]. Meanwhile participation of surface phenyl groups of PhMS-c in this interaction is confirmed by FTIR spectra presented in Fig. 6. Comparison of the spectra of PhMS-c (spectrum 2) with its composite with molsidomine (spectrum 3) shows that the band at 1434 cm−1 assigned to the C_C stretching vibrational mode [19,20] and the band at 750 cm−1 assigned to out-of-plane C\H bending [21] of the silica phenyl groups are shifted towards lower frequencies. This indicates the involvement of the phenyl groups in the interaction with molsidomine. The same changes in spectra are observed for the drug composite with PhMS-g [12]. Thus, the interaction between the π-systems of molsidomine and the phenyl modified silica materials plays important role in quantitative adsorption of the drug. As has been mentioned above, this work studied the phenyl modified mesoporous silica materials that were prepared by different methods (co-condensation and grafting). It is likely that the difference in the adsorption capacity of PhMS-c and PhMS-g is due to a different accessibility of phenyl groups for adsorption interactions with molsidomine molecules. According to literature data [22,23], the grafted groups are mainly located at the pore openings whereas the incorporated groups in PhMS-c sample are mainly located on the pore walls. Therefore,
Fig. 4. Correlations between the qmax value and the parameter of porous structure (a) and concentration of surface groups (b) of the silica materials.
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Fig. 5. UV spectra of molsidomine (1) and suspension of its composite with PhMS-c (2) in solution at pH 7.4.
PhMS-g contains a higher amount of phenyl groups which are accessible for interaction with molsidomine than PhMS-c. However the spectra presented in Figs. 5 and 6 show that π–π interaction is not a single type of interactions responsible for the drug adsorption. As can be seen in Fig. 5, a blue shift of the band assigned
to n → π* electronic transition (from 229 nm to 223 nm) testifies about the interaction of N6-exocyclic group of molsidomine with the silica material. According to literature data, the hypsochromic shift of the band of n → π* electronic transition can be due to hydrogen bonding between solute molecule and their environment (solvent, xerogel) [24,25]. Because the surfaces of PhMS-c and PhMS-g contain both phenyl groups and hydroxyl groups, hydrogen bonds may be formed between the hydroxyl groups of the adsorbents and electron donating atoms of the exocyclic groups of molsidomine. This is confirmed by red shifts of C_O stretching vibrations [17] (from 1651 cm−1 to 1645 cm−1) and C_N stretching vibrations [15] (from 1562 cm−1 to 1545 cm−1) as well as by a shift of Si\O (Si\OH) stretching vibrations [26] (from 960 cm−1 to 971 cm−1) in FTIR spectra of the composite of PhMS-c with molsidomine (Fig. 6, spectrum 3) in comparison with crystal molsidomine (Fig. 6, spectrum 1) and the adsorbent (Fig. 6, spectrum 2). The similar shift of characteristic bands attributed to hydrogen bonding was observed in FTIR spectra at adsorption of itraconazole on SBA-15 [27] or atrazine on amorphous silica [28]. Thus, the adsorption of molsidomine on the phenyl modified silica materials occurs mainly due to both π–π interaction and hydrogen bonding (Fig. 7). Surfaces of UMS, MMS and AMS contain only acid–base groups which are able to form hydrogen bonds with molsidomine molecules. As an example, Fig. 8 demonstrates FTIR spectra testifying about the adsorption of molsidomine molecules onto UMS through hydrogen
Fig. 6. FTIR spectra of crystal molsidomine (1), PhMS-c (2) and their composite (3).
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silanol groups of UMS and the drug molecules. Acidity (or proton donating ability) of the surface groups decreases in the following order [29]: SH N OH N NH. That results in decreasing qmax value in the order of the adsorbents. 3.2. Effect of pH on adsorption capacity of the silica materials
Fig. 7. Schematic illustration of the interactions responsible for molsidomine adsorption onto phenyl modified silica.
bonding. Like the spectra presented in Fig. 7, red shifts of C_O stretching vibrations [17] (from 1651 cm−1 to 1644 cm−1) and C_N stretching vibrations [17] (from 1562 cm−1 to 1547 cm−1) as well as by a shift of Si\O (Si\OH) stretching vibrations [26] (from 960 cm−1 to 969 cm− 1) are observed in FTIR spectra of the composite of UMS with molsidomine in comparison with crystal molsidomine and the adsorbent. This indicates the formation of hydrogen bonds between
The surfaces of the synthesized silica materials contain acid–base groups and molsidomine molecule presents electronegative oxygen and nitrogen atoms. State of the surface functional groups as well as molsidomine molecules should be affected by solution pH. As has been mentioned in Introduction, state of molsidomine has been studied only in acidic solution [12]. To elucidate molsidomine behavior in a wide range of pH, acid–base titration of the drug solution was carried out. The titration curve is presented in Fig. 9. As can be seen in Fig. 10, in the studied pH region molsidomine undergoes two acid–base equilibria with рК1 = 3.2 и рК2 = 5.6. The isoelectric point (pI) is found to be 4.4. Thus, molsidomine molecules can exist as the cationic (M+), anionic (M−) species and neutral molecules. The cationic species are formed due to protonation of the exocyclic N6 atom [17]. Probably the anionic species are formed due to hydrolysis of molsidomine catalyzed by base [13]: the acyl carbon with positive partial charge will be attacked by OH− ion to form a state with negative charge.
Fig. 8. FTIR spectra of crystal molsidomine (1), UMS (2) and their composite (3).
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in this work is found to be 8.0. The supposition about the important role of coulomb interaction is confirmed by the fact that the adsorption of molsidomine is insignificant at pH 4.8 when the amount of anionic species of molsidomine is low and at pH 8.0 when AMS surface is uncharged. 4. Conclusion Thus, in the present work the adsorption ability of mesoporous silica materials having various surface functional groups in relation to molsidomine was studied at different pH values. It has been found that the parameters of porous structure of the silica materials as well as the amount of the incorporated surface functional groups are not crucial factors determining adsorption capacities of the silica materials. The amount of adsorbed molsidomine is affected by the method of preparation of the silica materials, chemistry of their surfaces and solution pH from what adsorption is carried out. Practically at all studied pH the adsorption capacity of the synthesized materials decreases in the following order: Fig. 9. Acid–base titration curve of molsidomine solution (0.01 M) by KOH (0.01 M) and HCl (0.01 M) at 298 K.
The acid–base surface groups of the adsorbents can also be protonated or deprotonated at different pH values. Turning back to Fig. 3, it can be noted that at pH 4.8 (near molsidomine pI = 4.4) a greater portion of molsidomine molecules are neutral and the acid–base surface groups are protonated. This promotes the formation of hydrogen bonds between the molsidomine (proton acceptor) and surface groups (proton donors). The portion of neutral molecules of molsidomine decreases and the amount of molsidomine anionic species increases with increasing pH. At the same time under this condition the surface groups are charged negatively due to deprotonation. A number of adsorption sites able to form hydrogen bonds decrease resulting in decreasing qmax with increasing pH. The adsorption behavior of AMS for molsidomine differs from the other studied silica materials. AMS adsorbs the lowest amount of the drug and only at pH 7.4. It is possible that the molsidomine adsorption onto AMS occurs mainly due to coulomb interaction (Fig. 10). At pH 7.4 molsidomine exists in the anionic form and the aminopropyl surface groups of AMS are partially protonated because its pHZPC obtained
Fig. 10. Schematic illustration of coulombic interaction between molsidomine and AMS at pH 7.4.
PhMS‐g N PhMS‐c N MMS N UMS ≫ AMS: The most efficient adsorption of molsidomine is observed onto phenyl modified silica prepared by grafting at pH 4.8. AMS adsorbs the lowest amount of molsidomine and the adsorption was observed only at pH 7.4. The adsorption onto phenyl modified silica materials is driven by π–π interaction and hydrogen bonding. It is possible that coulomb interaction is responsible for the adsorption onto AMS. The pH has influence on the states of molsidomine and surface acid–base groups of the silica materials. Therefore, the adsorption capacity decreases with increasing pH. Supplementary data to this article can be found online at http://dx. doi.org/10.1016/j.msec.2014.03.052. References [1] Y.-F. Zhu, J.-L. Shi, Y.-S. Li, H.-R. Chen, W.-H. Shen, X.-P. Dong, Hollow mesoporous spheres with cubic pore network as a potential carrier for drug storage and its in vitro release kinetics, J. Mater. Res. 20 (2005) 54–61. [2] F. Qu, G. Zhu, S. Huang, S. Li, J. Sun, D. Zhang, S. Qiu, Controlled release of Captopril by regulating the pore size and morphology of ordered mesoporous silica, Microporous Mesoporous Mater. 92 (2006) 1–9. [3] Q. Tanga, Y. Xu, D. Wu, Y. Sun, A study of carboxylic-modified mesoporous silica in controlled delivery for drug famotidine, J. Solid State Chem. 179 (2006) 1513–1520. [4] G. Wang, A.N. Otuonye, E.A. Blair, K. Denton, Z. Tao, T. Asefa, Functionalized mesoporous materials for adsorption and release of different drug molecules: a comparative study, J. Solid State Chem. 182 (2009) 1649–1660. [5] M. Moritz, M. Łaniecki, Modified SBA-15 as the carrier for metoprolol and papaverine: adsorption and release study, J. Solid State Chem. 184 (2011) 1761–1767. [6] A. Szegedi, M. Popova, I. Goshev, J. Mihály, Effect of amine functionalization of spherical MCM-41 and SBA-15 on controlled drug release, J. Solid State Chem. 184 (2011) 1201–1207. [7] N. Suriyanon, P. Punyapalakul, C. Ngamcharussrivichai, Mechanistic study of diclofenac and carbamazepine adsorption on functionalized silica-based porous materials, Chem. Eng. J. 214 (2013) 208–218. [8] T.X. Bui, H. Choi, Adsorptive removal of selected pharmaceuticals by mesoporous silica SBA-15, J. Hazard. Mater. 168 (2009) 602–608. [9] M. Xie, H. Shi, K. Ma, H. Shen, B. Li, S. Shen, X. Wang, Y. Jin, Hybrid nanoparticles for drug delivery and bioimaging: mesoporous silica nanoparticles functionalized with carboxyl groups and a near-infrared fluorescent dye, J. Colloid Interface Sci. 395 (2013) 306–314. [10] N.A. Alyoshina, E.V. Parfenyuk, Effect of surface properties of mesoporous silica on adsorption of mesoionic compound molsidomine, J. Mater. Res. 27 (2012) 2858–2866. [11] N.A. Alyoshina, E.V. Parfenyuk, Functionalized mesoporous silica materials for molsidomine adsorption: Thermodynamic study, J. Solid State Chem. 205 (2013) 211–216. [12] E.S. Dolinina, E.V. Parfenyuk, The effects of surface chemistry of mesoporous silica materials and solution pH on kinetics of molsidomine adsorption, J. Solid State Chem. 209 (2014) 105–112. [13] U. Asahi, K. Shinozaki, M. Nagaoka, Chemical and kinetic study on stabilities of 3-morpholinosydnonimine and its N-ethoxycarbony1 derivative, Chem. Bull. Pharm. 19 (1971) 1079–1088. [14] Y. Wei, J. Xu, H. Dong, J.H. Dong, K. Qiu, S.A. Jansen-Varnum, Preparation and physisorption characterization of D-glucose-templated mesoporous silica sol–gel materials, Chem. Mater. 11 (1999) 2023–2029.
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Contents lists available at ScienceDirect
Materials Science and Engineering C journal homepage: www.elsevier.com/locate/msec
Comparative study of adsorption capacity of mesoporous silica materials for molsidomine: Effects of functionalizing and solution pH N.A. Alyoshina, A.V. Agafonov, E.V. Parfenyuk ⁎ G.A. Krestov Institute of Solution Chemistry of Russian Academy of Sciences, 1 Akademicheskaya Str., Ivanovo, Russian Federation
a r t i c l e
i n f o
Article history: Received 29 October 2013 Received in revised form 11 February 2014 Accepted 21 March 2014 Available online 30 March 2014 Keywords: Mesoporous silica Surface functional groups Molsidomine Solution pH Adsorption interactions
a b s t r a c t Adsorption capacities of mesoporous silica materials having various surface functional groups (hydroxyl, phenyl, mercaptopropyl, aminopropyl) at pH values of 4.8, 7.4, and 8.0 were studied. It was found that the maximum amount of adsorbed molsidomine is affected by method of preparation of the silica materials, chemistry of their surfaces and solution pH from where adsorption is carried out. The effects were explained by different states of the adsorbents and molsidomine in solution at the studied pH. The most efficient adsorption of molsidomine is observed onto phenyl modified silica prepared by grafting at pH 4.8. Aminopropyl modified silica adsorbs the lowest amount of molsidomine and the adsorption was observed only at pH 7.4. Interactions responsible for the adsorption were elucidated by spectroscopic studies. © 2014 Elsevier B.V. All rights reserved.
1. Introduction Studies of drug adsorption on porous silica materials can be of interest for the development of new technologies of waster treatment, purification of drugs and separation of their mixtures, quantitative determination of drugs in blood plasma, creation of new drug formulations with improved therapeutic and consumer properties, etc. Adsorption capacity of the materials is one of the most important characteristics in such applications. Adsorption capacity depends on parameters of porous structure of adsorbents (pore size and volume, specific area). It is clear, for example, that very small pore diameter (with respect to drug molecule size) does not promote high adsorption [1,2]. According to numerous studies, adsorption capacity of porous silica materials can be improved significantly by functionalizing their surfaces with judiciously chosen organic groups [3–7]. The functionalizing promotes surface–drug interactions and therefore, leads to improved adsorption capacity of the materials for drug molecules. The results show that the higher the concentration of functional groups, the better adsorption of drug is observed [3,6]. However in some cases the type of functional groups and not their density in the materials is mainly responsible for the differences in adsorption capacity of materials [5]. Another factor affecting adsorption capacity is properties of medium from what adsorption occurs. The pH value of a solution is one of the most important parameters affecting the adsorption process [7–9]. In fact, solution pH affects both surface binding sites of the adsorbent ⁎ Corresponding author. E-mail address: [email protected] (E.V. Parfenyuk).
http://dx.doi.org/10.1016/j.msec.2014.03.052 0928-4931/© 2014 Elsevier B.V. All rights reserved.
and state of drug molecules in solution. A change in pH may result in a change in charge profile of adsorbent species, which has effects on the interactions between adsorbate species and adsorbent. Depending on the nature of surface functional groups, adsorbent may be neutral (pH = pHpzc, at point of zero charge), positively (pH b pHpzc) or negatively (pH N pHpzc) charged due to protonation or dissociation of the functional groups. On other hand, because drugs are often weak electrolytes, they have ionizable functional groups that depend on pH values. Therefore, pH value is one of the most important factors controlling adsorption interactions and hence, adsorption capacity. This is confirmed by the results of experimental studies. For example, the adsorption capacities of mesoporous silica materials (unfunctionalized (HMS) and mercapto-(M-HMS) and amino-functionalized (A-HMS)) for diclofenac and carbamazepine are dependent on the pH, being highest at pH 5, due to the optimal electrostatic interactions and hydrogen bonding at this pH [7]. Efficiency of SBA-15 as adsorbent for series of pharmaceuticals is also dependent on pH [8]. The results of this work showed that SBA-15 is very effective adsorbent for the studied pharmaceuticals in acidic media and their adsorption is mainly controlled by hydrophilic interactions between functional groups in pharmaceutical molecules and silanol groups on silica surface, rather than a hydrophobic sorption. In this study, adsorption capacity of mesoporous silica materials with various surface functional groups (hydroxyl, mercaptopropyl, aminopropyl, phenyl) for drug molsidomine is studied at different pH values. The work is a continuation and extension of our previous studies [10–12] devoted to the development of efficient technology of the drug adsorption onto porous silica materials. Because all materials under study contain acid–base surface groups, a change in pH can affect the drug adsorption.
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2.2. Syntheses of the silica materials
Fig. 1. Molecular structure of molsidomine.
Molsidomine (N-(ethoxycarbonyl)-3-(4-morpholino)sydnonimine) is the drug used clinically for therapy of cardiovascular diseases. Chemically it belongs to the class of sydnonimines and has mesoionic nature. Structural formula of molsidomine is presented in Fig. 1. It has been found that molsidomine is stable in acid and neutral solutions. Titration of aqueous molsidomine with 1 N HCl allows the estimation of pKa that was found to be 3.34 at 298 K [13]. In extreme alkaline solutions, it decomposes to the carboxylate, ammonia, and monoethyl carbonate, which further decomposes to ethanol and carbon dioxide [13]. Due to the presence of heterocycle in its molecule, molsidomine exhibits aromatic properties. On the other hand, as mesoionic compound, molsidomine is highly polar and should favor strong hydrophilic interactions (for example, electrostatic, ion-dipole, hydrogen bonding) which will be affected by pH. It is impossible to establish a priori what interactions will be responsible for efficient molsidomine adsorption. Therefore, the aim of the present work is three-fold: to compare the adsorption capacities of the synthesized silica materials for molsidomine at different pH values, to elucidate the interactions responsible for the adsorption and to choose the most efficient adsorbent and favorable condition for the adsorption.
Unmodified silica (UMS) was synthesized by acid catalyzed hydrolysis and base catalyzed polycondensation of TEOS in the presence of D-glucose as structure-forming agent as described in [14]. The template as 50 wt.% D-glucose solution (4.2 g of D-glucose in 4.2 g of distilled water) was added after neutralization of the prehydrolyzed TEOS sol. The procedure of one-pot synthesis of phenyl-modified silica (PhMS-c) was similar to that described above. The phenyl functionality is introduced into the silica framework by the simultaneous addition of TEOS and PhTMOS in a molar ratio of 0.95:0.05 [15]. The as-synthesized samples were washed by hot water and centrifuged triply to remove D-glucose and then dried at in an oven at 120 °C overnight. FTIR spectra showed that the removal of glucose was complete. Mercaptopropyl and aminopropyl functionalized silica materials (MMS and AMS) were prepared by grafting. Phenyl modified silica material (PhMS-g) was also prepared by grafting. The modifier (MTMOS, APTES, PhTMOS; 1.5 ml) was added to an ethanolic suspension of UMS particles (5 g in 150 mL). The suspension was stirred at room temperature for 20 h. The sample was finally centrifuged and washed two times in ethanol. 2.2.1. Adsorption experiments Typically, 0.3 g of the synthesized mesoporous silica and 67 mL of molsidomine solution in buffer were mixed and stirred for 5 h in a temperature-controlled cell (T = 298 K) and after centrifugation for 15 min at 10 000 rpm the supernatant was analyzed with UV–Vis absorption spectrometer Agilent 8453 by monitoring the major peak at 310 nm, which corresponds to the absorption maximum of molsidomine. The initial concentration of molsidomine was changed from 0.016 · 10−3 to 0.158 · 10−3 mmol·ml−1. The surface concentrations of the adsorbed molsidomine were calculated according to the equation qe ¼
ðС 0 −C s Þ V ; m
ð1Þ
where qe is the surface molsidomine concentration (mmol·g−1), C0 and Cs are the bulk molsidomine concentrations before and after adsorption (mmol·ml−1), V is a volume (ml), and m is a mass of the adsorbent sample (g). The estimated relative error in qe is found to be 3%.
2. Experimental 2.1. Materials Tetraethoxysilane (TEOS) (high purity grade, Russia), 3aminopropyltriethoxysilane (APTES) (Aldrich, 99%), phenyltrimethoxysilane (PhTMOS) (Acros, 85%), mercaptopropyl trimethoxysilane (MTMOS) (Aldrich, 95%), D-glucose (ICN Biomedicals, N99% purity), and molsidomine (N-(ethoxycarbonyl)-3-(4-morpholino)sydnonimine) (Aldrich) were used without further purification. Sodium hydrogen phosphate and sodium dihydrogen phosphate (Russia, analytical grade) were used to prepare buffer solutions (pH 4.8, 7.4, 8.0) on the basis of doubly distilled deionized water. Sodium chloride (ChemMed, purity grade, Russia) and potassium bromide (Acros, 99+%, IR grade) were dried at 250 °C before use.
2.2.2. FTIR spectroscopy FTIR spectra of crystal molsidomine, the synthesized silica materials and their composites with the drug were recorded using an Avatar 360 FT-IR ESP spectrometer at room temperature. The spectra were recorded in the range of 4000 to 400 cm−1. The samples were examined as KBr disks. 2.2.3. Acid–base titration of molsidomine solution Acid–base properties of molsidomine were investigated by potentiometric titration method. Molsidomine solution (0.01 M) was divided into two portions. One of them was titrated by 0.01 M solution of KOH
Table 1 Parameters of porous structure and concentrations of surface groups of silica materials [10–12]. Samples
Specific surface area, m2/g
Total pore volumea, cm3/g
Average pore sizeb, nm
Concentration of incorporated organic surface groups mmol/g
UMS PhMS-c PhMS-g AMS MMS a b c
694 640 626 403 563
0.53 0.57 0.50 0.32 0.48
2.8 3.1 2.7 2.6 2.6
The single point pore volume determined at P/P0 = 1. Pore diameter according to the maximum of the BJH pore size distribution calculated from the desorption branch of the isotherm. Concentration of surface silanol groups.
c
6.62 0.54 0.47 1.40 0.14
mmol/m2 9.5 8.5 7.5 3.5 2.5
· · · · ·
10−3c 10−4 10−4 10−3 10−4
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Table 2 Isotherm models and their parameters of the synthesized silica materials for molsidomine adsorption at different pH values at 298 K. Model
Parameters
UMS
PhMS-c
PhMS-g
MMS
AMS
pH 4.8 max K L C e Langmuir qe ¼ q1þK L Ce
Freundlich qe = KF ⋅ C1/n e 1=n
e Sips qe ¼ qmax K S C1=n
1þK S C e
Redlich–Peterson qe ¼
K R−P C e 1þα R−P C βe
max K L C e Langmuir qe ¼ q1þK L Ce
Freundlich qe = KF ⋅ C1/n e 1=n
e Sips qe ¼ qmax K S C1=n
1þK S C e
Redlich–Peterson qe ¼
K R−P C e 1þα R−P C βe
max K L C e Langmuir qe ¼ q1þK L Ce
Freundlich qe = KF ⋅ C1/n e 1=n
e Sips qe ¼ qmax K S C1=n
1þK S C e
Redlich–Peterson qe ¼
K R−P C e 1þα R−P C βe
qmax, (mmol·g−1) KL, (L·g−1) R2 KF, (mmol1 − 1/n·L1/n·g−1) 1/n R2 qmax, (mmol·g−1) Ks, (L·g−1)1/n 1/n R2 KR-P, (L·g−1) αR-P, (L·g−1)β β R2
1.47 · 10−3 0.36 · 104 0.9962 0.471 0.77 0.9824 1.26 · 10−3 0.89 · 104 1.07 0.9965 4.582 27.5 · 109 2.81 0.9667
4.21 · 10−3 0.58 · 104 0.9942 1.245 0.73 0.9372 1.56 · 10−3 129 · 105 0.63 0.9978 24.137 24 · 106 1.88 0.9844
4.65 · 10−3 0.87 · 104 0.9829 0.574 0.61 0.9483 2.65 · 10−3 75.5 · 105 0.64 0.9983 36.496 1.59 · 106 1.59 0.9907
2.22 · 10−3 0.21 · 104 0.9770 0.069 0.42 0.9082 1.64 · 10−3 564 · 105 0.59 0.9986 38.023 3.68 · 105 1.34 0.9952
–
qmax, (mmol·g−1) KL, (L·g−1) R2 KF, (mmol1 − 1/n·L1/n·g−1) 1/n R2 qmax, (mmol·g−1) Ks, (L·g−1)1/n 1/n R2 KR-P, (L·g−1) αR-P, (L·g−1)β β R2
pH 7.4 2.14 · 10−3 0.56 · 104 0.9902 0.582 0.72 0.9709 1.09 · 10−3 24.9 · 105 0.67 0.9969 11.265 59.2 · 105 1.78 0.9912
3.72 · 10−3 0.58 · 104 0.9432 0.496 0.65 0.9380 1.75 · 10−3 92.7 · 105 0.62 0.9958 19.635 15.4 · 106 1.88 0.9632
1.48 · 10−3 3.64 · 104 0.9901 0.069 0.45 0.9149 1.29 · 10−3 6.20 · 105 0.81 0.9979 48.820 0.94 · 105 1.11 0.9806
1.20 · 10−3 1.13 · 104 0.9726 0.111 0.54 0.9118 0.90 · 10−3 16.0 · 106 0.62 0.9974 15.017 17.5 · 105 1.57 0.9970
0.72 · 10−3 1.33 · 104 0.9834 0.048 0.52 0.9202 0.48 · 10−3 44.6 · 106 0.58 0.9945 7.373 50 · 106 1.96 0.9860
qmax, (mmol·g−1) KL, (L·g−1) R2 KF, (mmol1 − 1/n·L1/n·g−1) 1/n R2 qmax, (mmol·g−1) Ks, (L·g−1)1/n 1/n R2 KR-P, (L·g−1) αR-P, (L·g−1)β β R2
pH 8.0 1.01 · 10−3 0.66 · 104 0.9911 0.197 0.68 0.9430 0.48 · 10−3 11.2 · 106 0.62 0.9980 6.180 5.44 · 107 2.00 0.9960
1.38 · 10−3 2.26 · 104 0.9957 0.093 0.49 0.9618 1.35 · 10−3 5.0 · 104 0.93 0.9948 27.248 0.50 · 105 1.11 0.9962
1.29 · 10−3 1.15 · 104 0.8981 0.045 0.46 0.8288 0.73 · 10−3 2.13 · 1011 0.39 0.9948 10.748 3.13 · 108 2.19 0.9910
1.35 · 10−3 0.31 · 104 0.9952 0.244 0.72 0.9342 0.40 · 10−3 5.86 · 108 0.59 0.9985 3.961 3.26 · 1010 2.79 0.9664
–
–
–
–
–
–
–
and the other portion was titrated by 0.01 M solution of HCl. In all titrations, the solution was stirred for 20 min after each addition of acid or base and the pH was measured with a pH/ION Analyzer Radelkis (Budapest). 2.2.4. Determination of zero point charge (pHZPC) of the silica material The point of zero charge of AMS sample was determined by the batch equilibration method [16], using NaCl aqueous solution (0.01 M) as a background electrolyte. The NaCl solution was placed into series of vials, 50 ml per vial, which initial pH values (pHi) were adjusted by 0.01 M KOH or 0.01 M HCl. 0.1 g sample of the AMS was introduced in each vial. The suspensions were stirred for 0.5 h and the equilibrium pH value (pHe) was measured. The dependence of ΔpH = pHe − pHi on pHi allows the determination of the pHZPC value. The measurements were carried out with a pH/ION Analyzer Radelkis (Budapest). The obtained pHZPC of AMS is found to be 8.0. 3. Results and discussion In our previous work [10,11] we have showed that the synthesized silica materials are amorphous and mesoporous and have high specific area and pore volume. The concentration of surface organic groups of
Fig. 2. Comparison of different isotherm models for molsidomine adsorption on PhMS-c at pH 7.4: 1—Langmuir model; 2—Freundlich model; 3—Sips model; 4—Redlich–Peterson model.
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Fig. 3. Effect of solution pH on molsidomine adsorption onto the synthesized silica materials at 298 K: 1 — UMS, 2 — PhMS-c, 3 — PhMS-g, and 4 — MMS.
the functionalized silica materials was estimated from elemental analysis data and the concentration of hydroxyl groups of UMS was estimated by thermal analysis method [10–12]. The parameters of porous structure and concentrations of the surface groups are presented in Table 1. In order to discover the adsorption capacity of the synthesized silica materials for molsidomine, the experimental data points were fitted to the Langmuir, Freundlich, Redlich–Peterson and Sips (Langmuir– Freundlich) empirical models which are the most frequently used two- and thee-parameter equations in the literature describing the non-linear equilibrium between adsorbed drug and in solution at a constant temperature. The isotherm equations and their parameters at all studied pH values are given in Table 2. By comparing the correlation coefficients (R2) for the four models at different pH values, it can be inferred that the isotherms are more adequately fitted by the Sips model. As an example, Fig. 2 demonstrates comparison of different isotherm models for molsidomine adsorption on PhMS-c at pH 7.4.
3.1. Effect of surface chemistry on adsorption capacity of the silica materials. Interactions that are responsible for molsidomine adsorption Fig. 3 shows the qmax trend at different pH values for molsidomine adsorption on the silica materials. As can be seen from this figure, practically at all studied pH values the highest adsorption capacity is observed on phenyl modified silica materials (PhMS-g and PhMS-c). AMS exhibits the lowest adsorption capacity for molsidomine. It should be noted that no correlation is observed between the qmax value and both the parameters of porous structure and concentration of the incorporated surface groups (Fig. 4. As an example, Fig. 4(a) demonstrates the correlation between the qmax value and the total pore volume value. No correlation was observed between the qmax and the surface area. Therefore, it may be supposed that aromatic groups of the phenyl modified silica materials contribute significantly to efficient adsorption of molsidomine on these adsorbents. Because the adsorbents contain surface phenyl groups and molsidomine molecules contain electron
deficient heterocycle, π–π interaction may occur between them. This supposition was confirmed by spectral studied. As an example, Fig. 5 shows UV spectra of molsidomine and suspensions of its composites with PhMS-c in a solution at pH 7.4. As can be seen in Fig. 5, two characteristic intensive bands are presented in the molsidomine spectrum (spectrum 1). The first band at 310 nm is assigned to π → π* electronic transition due to p–π conjugation in sydnonimine ring. The second band (229 nm) results from n → π* electronic transition and can be attribute to exocyclic group [17]. In the spectrum of the composite (spectrum 2) the first band exhibits a red shift (from 310 nm to 313 nm). The red shift of π → π* electronic transition band indicates that the sydnonimine heterocycle is involved in interaction with the adsorbent surface. Analogous changes in UV spectra were observed at interaction of phenanthrene with humic subunits [18]. Meanwhile participation of surface phenyl groups of PhMS-c in this interaction is confirmed by FTIR spectra presented in Fig. 6. Comparison of the spectra of PhMS-c (spectrum 2) with its composite with molsidomine (spectrum 3) shows that the band at 1434 cm−1 assigned to the C_C stretching vibrational mode [19,20] and the band at 750 cm−1 assigned to out-of-plane C\H bending [21] of the silica phenyl groups are shifted towards lower frequencies. This indicates the involvement of the phenyl groups in the interaction with molsidomine. The same changes in spectra are observed for the drug composite with PhMS-g [12]. Thus, the interaction between the π-systems of molsidomine and the phenyl modified silica materials plays important role in quantitative adsorption of the drug. As has been mentioned above, this work studied the phenyl modified mesoporous silica materials that were prepared by different methods (co-condensation and grafting). It is likely that the difference in the adsorption capacity of PhMS-c and PhMS-g is due to a different accessibility of phenyl groups for adsorption interactions with molsidomine molecules. According to literature data [22,23], the grafted groups are mainly located at the pore openings whereas the incorporated groups in PhMS-c sample are mainly located on the pore walls. Therefore,
Fig. 4. Correlations between the qmax value and the parameter of porous structure (a) and concentration of surface groups (b) of the silica materials.
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Fig. 5. UV spectra of molsidomine (1) and suspension of its composite with PhMS-c (2) in solution at pH 7.4.
PhMS-g contains a higher amount of phenyl groups which are accessible for interaction with molsidomine than PhMS-c. However the spectra presented in Figs. 5 and 6 show that π–π interaction is not a single type of interactions responsible for the drug adsorption. As can be seen in Fig. 5, a blue shift of the band assigned
to n → π* electronic transition (from 229 nm to 223 nm) testifies about the interaction of N6-exocyclic group of molsidomine with the silica material. According to literature data, the hypsochromic shift of the band of n → π* electronic transition can be due to hydrogen bonding between solute molecule and their environment (solvent, xerogel) [24,25]. Because the surfaces of PhMS-c and PhMS-g contain both phenyl groups and hydroxyl groups, hydrogen bonds may be formed between the hydroxyl groups of the adsorbents and electron donating atoms of the exocyclic groups of molsidomine. This is confirmed by red shifts of C_O stretching vibrations [17] (from 1651 cm−1 to 1645 cm−1) and C_N stretching vibrations [15] (from 1562 cm−1 to 1545 cm−1) as well as by a shift of Si\O (Si\OH) stretching vibrations [26] (from 960 cm−1 to 971 cm−1) in FTIR spectra of the composite of PhMS-c with molsidomine (Fig. 6, spectrum 3) in comparison with crystal molsidomine (Fig. 6, spectrum 1) and the adsorbent (Fig. 6, spectrum 2). The similar shift of characteristic bands attributed to hydrogen bonding was observed in FTIR spectra at adsorption of itraconazole on SBA-15 [27] or atrazine on amorphous silica [28]. Thus, the adsorption of molsidomine on the phenyl modified silica materials occurs mainly due to both π–π interaction and hydrogen bonding (Fig. 7). Surfaces of UMS, MMS and AMS contain only acid–base groups which are able to form hydrogen bonds with molsidomine molecules. As an example, Fig. 8 demonstrates FTIR spectra testifying about the adsorption of molsidomine molecules onto UMS through hydrogen
Fig. 6. FTIR spectra of crystal molsidomine (1), PhMS-c (2) and their composite (3).
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silanol groups of UMS and the drug molecules. Acidity (or proton donating ability) of the surface groups decreases in the following order [29]: SH N OH N NH. That results in decreasing qmax value in the order of the adsorbents. 3.2. Effect of pH on adsorption capacity of the silica materials
Fig. 7. Schematic illustration of the interactions responsible for molsidomine adsorption onto phenyl modified silica.
bonding. Like the spectra presented in Fig. 7, red shifts of C_O stretching vibrations [17] (from 1651 cm−1 to 1644 cm−1) and C_N stretching vibrations [17] (from 1562 cm−1 to 1547 cm−1) as well as by a shift of Si\O (Si\OH) stretching vibrations [26] (from 960 cm−1 to 969 cm− 1) are observed in FTIR spectra of the composite of UMS with molsidomine in comparison with crystal molsidomine and the adsorbent. This indicates the formation of hydrogen bonds between
The surfaces of the synthesized silica materials contain acid–base groups and molsidomine molecule presents electronegative oxygen and nitrogen atoms. State of the surface functional groups as well as molsidomine molecules should be affected by solution pH. As has been mentioned in Introduction, state of molsidomine has been studied only in acidic solution [12]. To elucidate molsidomine behavior in a wide range of pH, acid–base titration of the drug solution was carried out. The titration curve is presented in Fig. 9. As can be seen in Fig. 10, in the studied pH region molsidomine undergoes two acid–base equilibria with рК1 = 3.2 и рК2 = 5.6. The isoelectric point (pI) is found to be 4.4. Thus, molsidomine molecules can exist as the cationic (M+), anionic (M−) species and neutral molecules. The cationic species are formed due to protonation of the exocyclic N6 atom [17]. Probably the anionic species are formed due to hydrolysis of molsidomine catalyzed by base [13]: the acyl carbon with positive partial charge will be attacked by OH− ion to form a state with negative charge.
Fig. 8. FTIR spectra of crystal molsidomine (1), UMS (2) and their composite (3).
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in this work is found to be 8.0. The supposition about the important role of coulomb interaction is confirmed by the fact that the adsorption of molsidomine is insignificant at pH 4.8 when the amount of anionic species of molsidomine is low and at pH 8.0 when AMS surface is uncharged. 4. Conclusion Thus, in the present work the adsorption ability of mesoporous silica materials having various surface functional groups in relation to molsidomine was studied at different pH values. It has been found that the parameters of porous structure of the silica materials as well as the amount of the incorporated surface functional groups are not crucial factors determining adsorption capacities of the silica materials. The amount of adsorbed molsidomine is affected by the method of preparation of the silica materials, chemistry of their surfaces and solution pH from what adsorption is carried out. Practically at all studied pH the adsorption capacity of the synthesized materials decreases in the following order: Fig. 9. Acid–base titration curve of molsidomine solution (0.01 M) by KOH (0.01 M) and HCl (0.01 M) at 298 K.
The acid–base surface groups of the adsorbents can also be protonated or deprotonated at different pH values. Turning back to Fig. 3, it can be noted that at pH 4.8 (near molsidomine pI = 4.4) a greater portion of molsidomine molecules are neutral and the acid–base surface groups are protonated. This promotes the formation of hydrogen bonds between the molsidomine (proton acceptor) and surface groups (proton donors). The portion of neutral molecules of molsidomine decreases and the amount of molsidomine anionic species increases with increasing pH. At the same time under this condition the surface groups are charged negatively due to deprotonation. A number of adsorption sites able to form hydrogen bonds decrease resulting in decreasing qmax with increasing pH. The adsorption behavior of AMS for molsidomine differs from the other studied silica materials. AMS adsorbs the lowest amount of the drug and only at pH 7.4. It is possible that the molsidomine adsorption onto AMS occurs mainly due to coulomb interaction (Fig. 10). At pH 7.4 molsidomine exists in the anionic form and the aminopropyl surface groups of AMS are partially protonated because its pHZPC obtained
Fig. 10. Schematic illustration of coulombic interaction between molsidomine and AMS at pH 7.4.
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