Article pubs.acs.org/Langmuir
Adsorption and Detection of Sport Doping Drugs on Metallic Plasmonic Nanoparticles of Different Morphology Irene Izquierdo-Lorenzo, Irene Alda, Santiago Sanchez-Cortes,* and José Vicente Garcia-Ramos Instituto de Estructura de la Materia, IEM-CSIC, Serrano, 121, 28006-Madrid, Spain S Supporting Information *
ABSTRACT: A comparative study of different plasmonic nanoparticles with different morphologies (nanospheres and triangular nanoprisms) and metals (Ag and Au) was done in this work and applied to the ultrasensitive detection of aminoglutethimide (AGI) drug by surface enhanced Raman spectroscopy (SERS) and plasmon resonance. AGI is an aromatase inhibitor used as an antitumoral drug with remarkable pharmacological interest and also in illegal sport doping. The application of very sensitive spectroscopic techniques based on the localization of an electromagnetic field on plasmonic nanoparticles confirms the previous study of the adsorption of drugs onto a metal surface due to the near field character of these techniques. The adsorption of AGI on the above substrates was investigated at different pH values and surface coverages, and the results were analyzed on the basis of AGI/metal affinity, considering the interaction mechanism, the existence of two binding sites in AGI, and the influence of the interface on the adsorption in terms of surface charge due to the presence of other ions linked to the surface. Finally, a comparative quantitative detection of AGI was performed on both spherical and triangular nanoprism nanoparticles, and a limit of detection lower than those reported so far was deduced on the latter nanoparticles.
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INTRODUCTION Surface enhanced Raman spectroscopy (SERS) has seen constant growth since its discovery over 30 years ago. One of the most active areas of SERS is the development of effective substrates upon which sample molecules can be adsorbed giving rise to strong enhancement efficiencies and reproducibility.1,2 Its potential as an analytical technique has been widely studied, and SERS sensors have been developed for pollutants, insecticides, or drugs.3−5 The sensitivity and uniformity of the SERS response strongly depends on the morphology of the metal plasmonic surface, as well as on its surface chemistry, which can be modulated to enhance the applicability of these systems.6,7 The enhancement can be controlled by nanofabrication of the surface structure in terms of size, shape, and spacing of features of the surface to which the SERS analyte molecules bind. In this sense, nanofabrication keeps being a hot topic,8−10 so that new shapes and sizes of Au and Ag nanoparticles (NPs) are reported in the literature continuously as potential SERS substrates. Metal colloids have demonstrated to be one of the most active SERS substrates11 in spite of their instability. Dozens of new potentially active surfaces are synthesized by new methods every year, many of them based on silver and gold NP colloids. However, NP synthesis specialists do not often test the SERS efficiency of new surfaces, and given the © 2012 American Chemical Society
case, the employed probe molecules are mainly chosen for their strong SERS activity but are missing other applications. In particular, metal nanoplates have attracted attention in recent years due to their interesting plasmonic properties.12 In this sense, many different syntheses of colloidal silver triangular nanoprisms (TNAg) have been described, both by photochemical13−15 and thermal16−19 reduction processes. However, their ability to produce SERS enhancement is rarely tested, and when done, it is common to employ probe molecules that are known to give a strong SERS signal for any substrate, such as Rhodamine 6G (R6G), in order to refer impressive spectra and high enhancement factors.15,20 One of the main goals of the present work was the preparation of a TNAg colloid suitable for SERS experiments, without using strong capping agents.12 Another objective was the application of TNAg in the detection by SERS of nonresonant substances, displaying much lower SERS activity than R6G, to actually probe the potentiality of this substrate in real analytical applications. To perform this analysis, we have selected R-aminoglutethimide (AGI, Figure 1a), a compound with a high pharmacological interest. This substance is an Special Issue: Colloidal Nanoplasmonics Received: January 13, 2012 Revised: February 27, 2012 Published: February 27, 2012 8891
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MATERIALS AND METHODS
AgNO3, trisodium citrate, hydroxylamine hydrochloride, NaBH4, absolute ethanol, KBr, and KNO3 (all of analytical grade) were purchased from Merck. H2O2 (30%, puriss) and AGI (97%) were obtained from Aldrich. A stock solution of AGI in ethanol at a concentration of 0.2 M was prepared, and further dilutions were made under ethanol or Milli-Q water. Absolute ethanol was of analytical grade (99.5% purity) obtained from Merck. Raman spectra were registered with a Renishaw Raman RM2000, equipped with a charge-coupled device (CCD) camera, using a He/Ne 632.8 nm laser as the excitation source. A 785 nm laser line provided by a diode laser was also tested, but the resulting spectra did not show optimal intensity. So the Raman and SERS spectra shown in this paper correspond entirely to the spectra recorded at 632.8 nm. A UV−visible−near-infrared (UV−vis−NIR) Shimadzu 3600 spectrometer equipped with a photomultiplier (PMT) for light detection in the UV−visible range and an InGaAs detector for the near-infrared was employed to obtain the plasmon absorption spectra. Transmission electronic microscopy (TEM) micrographs were obtained by a JEOL-2100 operating at 200 kV. Samples for TEM were prepared by depositing a drop of the colloidal suspension on a CF400-Cu grid covered by a thin layer (30−50 nm) of pure carbon. Spherical Au NPs (SCAu) were prepared using the method described by Sutherland and Winefordner.32 Briefly, 0.1 mL of an aqueous solution of 0.118 M HAuCl4 was diluted in 40 mL of water, under intense stirring. One milliliter of sodium citrate solution at 1% in volume was added dropwise. The yellow solution was refluxed for 5 min, resulting in a red colloidal suspension. Spherical Ag NPs were prepared by reduction of silver nitrate with three different reduction agents: trisodium citrate dehydrate, hydroxylamine hydrochloride, and sodium borohydride. Citrate Ag NPs (SCAg) were obtained by the following procedure.33 A total of 1 mL of a 1% w/v trisodium citrate aqueous solution was added to 50 mL of a boiling 10−3 M silver nitrate aqueous solution, and boiling was continued for 1 h. The colloid obtained showed a turbid gray appearance and had a final pH of 6.5. Hydroxylamine Ag NPs (SHAg) were obtained by the method described by Leopold and Lendl.34 A total of 300 μL of a sodium hydroxide solution (1 M) was added to 90 mL of a 6 × 10−2 M hydroxylamine hydrochloride solution. Then, 10 mL of a 1.11 × 10−3 M silver nitrate aqueous solution was added dropwise to the mixture under vigorous stirring. Borohydride Ag NPs (SBAg) were prepared by using NaBH4 as a reductor.35 A total of 10 mL of aqueous silver nitrate (10−3 M) was added, drop by drop to 30 mL of ice-cold aqueous sodium borohydride (2 × 10−2 M) and vigorously stirred. Triangular nanoprism-shaped Ag NPs (TNAg) were prepared by an adaptation of the method described by Cathcart et al.16 Forty milliliters of an aqueous solution containing 2.4 × 10−3 M sodium citrate, 1.2 × 10−4 M AgNO3, 2.6 × 10−2 M H2O2, and 6.5 × 10−7 M KBr was prepared in an erlenmeyer flask and cooled for 30 min. After this time, the mixture was placed in a cold water bath, and 480 μL of a freshly prepared NaBH4 0.1 M solution was added under vigorous stirring. The solution immediately turned a pale yellow color, as an indication of the silver seeds formation. After 2−3 min, the seed growth to form TNP started. The reaction was finished after 5 min and removed from stirring. Samples for SERS measurements were prepared as follows: 0.5 mL of a colloid was activated by the addition of KNO3 up to 0.03 M. Finally, an aliquot of an AGI stock solution was then added to the sample, and then SERS spectra were registered. In order to optimize reproducibility of the SERS experiments, the laser beam was focused inside a cuvette containing the sample. The SERS intensities registered for the quantitative study were acquired three times for each concentration, and normalized using the water band at 3400 cm−1 as an internal reference. Finally, the limit of detection (LOD) was calculated for a signal-to-noise ratio of 3. The enhancement factor (EF) was calculated according to the method described in ref 36 (see Supporting Information).
Figure 1. (a) Molecular structure of AGI. Adsorption models: (b) Ionic interaction through the AN moiety of AGIH+ protonated form, (c) coordination interaction through AN, (d) coordination interaction through GI, and (e) bidentate interaction through simultaneous coordination of AN and GI.
aromatase inhibitor used for breast cancer treatment in postmenopausical women.21 It is also included in the World Anti-Doping Agency Prohibited List,22 as it is consumed by bodybuilders to prevent the biosynthesis of estrogen and increase muscle mass. In sport doping analysis, both the drug identification (specificity) and their detection at low concentration levels (sensitivity) are crucial. Thus, SERS fulfils all requirements to become an efficient analytical method to use in sport doping tests. In a previous work we performed a detection study of AGI on Au NPs.23 In addition, a similar study was recently performed for a group of structurally related compounds: beta2adrenergic agonist (βAA) drugs clenbuterol, salbutamol, and terbutaline on metal surface,24 demonstrating the high potentiality of SERS in antidoping analysis. In order to quantitatively determine the presence of AGI, and thus, to control its illegal use, several methods have been described.25−31 The most extended analytical techniques applied for the detection of this drug are liquid chromatography−mass spectrometry (LC-MS) and capillary electrophoresis (CE). However, LC-MS requires analyte preconcentration for detecting low concentrations, and CE does not afford any molecular information about the structure of the studied compound, apart from the usual need of preconcentration. In this paper, we have performed a comparison study between several metal NPs commonly used in SERS experiments and TNAg colloids in relation to the adsorption and detection of AGI. To fulfill this objective, an in-depth study of the adsorption of AGI on the different metallic systems and at different pH and adsorbate concentration is required. This investigation was performed to extract key structural information concerning this drug and to determine the conditions at which the AGI sensing can be made at conditions of maximum efficiency. 8892
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RESULTS AND DISCUSSION Characterization of Metal NPs. TEM. Figure 2 shows the TEM images of the metal NPs tested in the detection of
predominant existence of spheroids and even nanorods in the case of SCAg.33 In this work we have centered our attention on the morphology of TNAg NPs, as these NPs have not been well characterized so far. TEM images of these NPs are shown in more detail in Figure 3. These NPs are mainly constituted by triangular nanoprisms with a side length of 36 ± 4 nm and 6.6 ± 0.6 nm of thickness. The corners of the triangles are not completely sharp. Additionally, 6% of hexagonal nanoprisms are also present in the colloid. TNAg aggregates (Figure 3b) appear mostly from stacking on the triangular facets. The observed mean distance between nanoprisms is ca. 1 nm (Figure 3c). These interparticle junctions can act as hot spots where the field intensification is very high. Plasmon Resonance. For spherical NPs, the plasmon resonance wavelength increases with the mean diameter in the sense SCAg > SHAg > SBAg (Table 1), showing maxima at 415, 400, and 390 nm, respectively (Figure 2). The extinction spectrum of TNAg colloid (Figure 2 and 4) shows three bands:39 at 339 nm due to resonances of the out-of-plane localized surface plasmons (LSPs), at 394 nm due to quadrupolar in-plane and dipolar out-of-plane LSPs, and the most intense at 538 nm due to dipolar in-plane LSPs. Additionally, the absorption band at 290 nm is due to internal transitions in the NO3− ion. The adsorption of AGI causes an aggregation of NPs in the colloidal suspensions with the appearance of a new absorption band at longer wavelengths (Figure 2), which are seen at 800, 702, and 660 nm in the case of SCAg, TNPAg, and SCAu respectively. In the case of SHAg and SBAg, the aggregation induced by AGI is very low, and the extinction spectrum almost did not change (spectra not shown). This secondary band is the actual SERS active plasmon resonance leading to the SERS intensification. Therefore, we checked the SERS intensity with two laser lines: 632.8 and 785 nm. In all cases, the most intense SERS intensities were measured at 632.8 nm, thus this line was finally employed to register all the SERS spectra shown here. The higher enhancement reached at the latter excitation wavelength is due to the better fit between both the excitation and the SERS emissions bands with the extinction corresponding to SERS active plasmon resonances of aggregated NPs (Figure SI1 in the Supporting Information). The adsorption process of AGI onto Ag and Au surfaces is a key factor that determines the possibility of observing a large SERS signal. This adsorption can in principle be monitored by the extinction spectra, as it induces the aggregation of NPs in the suspension. In the case of Ag, it is noteworthy to observe that the addition of AGI only induced NP aggregation when the pH of the medium was larger than 7, which suggests that only the deprotonated form of AGI can interact with the Ag surface. This can be assumed by taking into account that the extinction
Figure 2. Plasmon resonance spectra of (a) SCAg, (b) TNAg, and (c) SCAu NPs and TEM images of each colloid on the right. TEM micrographs of SHAg (d) and SBAg (e) NPs are also shown in the lower part for comparison.
AGI by SERS as long as the plasmon resonance spectra of the suspensions before and after their aggregation with AGI. The main morphological features of all these colloids are summarized in Table 1. SCAu and SBAg NPs have been extensively characterized in previous works37,38 and display a very homogeneous dispersion of NPs with a mean spherical shape. SHAg and SCAg NPs are the biggest NPs and show a less homogeneous dispersion of sizes and shapes, with
Table 1. Properties of the Fabricated Metal NPs and Enhancement Factors Deduced from the SERS Spectra of AGI Registered at pH = 6.0 substrate SCAg SHAg SBAg TNAg SCAu a
plasmon resonance/nm
size of NP/nma
NPs·mL−1
total adsorption surface (TAS) cm2·mL−1
EF
415 400 389 394/538 520
D = 50 ± 5 D = 45 ± 4 D = 15 ± 2 L = 36 ± 4W = 6.6 ± 0.6 D = 20 ± 3
1.56 × 10 2.14 × 1011 1,9 × 1012 3.21 × 1011 7.30 × 1011
± ± ± ± ±
1.01 × 10 3.5 × 103 2.5 × 102 7.0 × 106 9.0 × 105
11
12.3 13.6 13.4 6.04 9.17
2.5 2.6 3.5 1.2 3.0
EF/TAS 6
8.2 × 104 2.6 × 102 18.7 1.16 × 106 9.8 × 104
D = diameter of spheres, L = side length of triangle, W = width of nanoprisms. 8893
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Figure 4. Plasmon resonance spectrum of the TNAg colloid at different pH values in the presence of AGI (10−5 M). Inset: Variation of the absorbance at 702 nm at different pH values due to the aggregation induced by the neutral AGI. The pK of the deprotonation was calculated from the first derivative, also shown in the figure.
resulting SERS spectra. However, the measurement of a SERS signal from AGI requires the adsorbate approach to the metal surface to benefit from the electromagnetic near-field enhancement. This involves several processes: (a) diffusion to the surface, (b) adsorption, which usually also implies the removal of other chemical species adsorbed onto the surface, and (c) self-assembly on the interface. The adsorption is a key step in which aqueous substrates implies the chemical interaction with the surface, making necessary the existence of chemical groups showing some kind of affinity toward the metal. AGI has two possible binding sites: anilinic (AN) or glutarimide (GI), which determine the interaction mechanism with the metal surface (Figure 1). The SERS spectra of AGI are shown in Figure 5 at pH 6.0 on each plasmonic materials fabricated here, compared to the Raman of the solution in ethanol (Figure 5f), and normalized to the water band. The comparison of SERS spectra in Figure 5 with the Raman spectrum of the solution reveals a clear weakening or disappearance of the νCO band 1714 cm−1 (see Table 2 for assignment), thus indicating that the interaction with the metal through the imide group is always taking place. As a consequence of this interaction, the imide N−H bending band almost disappears on Ag, while on Au it is still visible at 1509 cm−1 (Figure 5d). In addition, strong aromatic bands (for instance, the band at 1606 cm−1) can be observed in all the SERS spectra, indicating a possible implication of AN moiety in the interaction or simply due to the higher cross section of aromatic groups in Raman versus the aliphatic GI moiety. A detailed analysis of the SERS spectra indicates that the relative intensity of bands corresponding to AN or GI can vary depending on the nature of the metal and the interface (Figure 5 and Table 2). For example, on Ag NPs, a certain amount of Ag+ ions is always present on the surface of the NPs, due to the relatively lower electric potential, thus favoring the interaction with certain groups in the adsorbed molecules of the NPs, and inducing the adsorption of a variety of anions from the solution.
Figure 3. TEM micrographs of TNAg NPs, (a) unaggregated and (b) aggregated with nitrate and AGI, showing two different views of TNAg aggregates (from the side and from the top). (c,d) Side view detail of stacked TNAg nanoprisms showing interparticle spaces where hot spots are possible.
spectrum of TNAg is not affected by the addition of OH− anions due to the presence of adsorbed bromide ions, which are not desorbed by OH− ions40 (Figure SI2 in the Supporting Information). We have centered our attention on the aggregation of TNAg NPs by plotting the intensity of the plasmon peaks of aggregated NPs (centered at 702 nm) versus pH (Figure 4). A sigmoidal leaning was observed that depends on the surface coverage of NPs by deprotonated AGI. From the latter dependence, a pKa of 8 can be deduced for AGI adsorbed on silver, by estimating the numerical second derivative of the sigmoidal fitting (inset in Figure 4). SERS Spectra and Adsorption of AGI onto Metallic Surfaces. The adsorption of AGI on the different metallic NPs employed here can be carefully studied by analyzing the 8894
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SERS efficiency, is modulated by factors such as the interface properties (electric potential, adsorbed ions, and surface coverage). Therefore, the interaction strength and its mechanism are expected to be different on each metallic substrate, thus determining a different SERS enhancement factor (EF). In Table 1, the total EF and the EF relative to the total adsorption surface (TAS) of all the analyzed substrates is shown. The highest relative enhancement (1.16 × 106) was found in the case of TNAg colloid, which can be attributed to the morphology of the NPs, as also reported in a previous study.41 SCAg and SCAu colloid rendered a similar enhancement, but higher than that deduced for SHAg. This is due to the higher negative electric potential existing in citrate-covered NPs, which seems to exert an attraction to positively charged AGI at pH 6.0. Finally, the SERS intensity on the SBAg colloid turned out to be very low. The different EF factor found in the case of spherical Ag NPs in the sense SCAg > SHAg > SBAg suggests a size dependence of the enhancement.42 Since the strongest EF was deduced for SCAg and TNAg colloids, these substrates were selected to carry out the SERS adsorption and detection of AGI at the different experimental conditions shown below aimed to understand the adsorption of AGI, and to establish the optimal measurement conditions for its ultrasensitive detection. Effect of pH. The pH of the suspension was previously demonstrated to have an important role in the adsorption and interaction mechanism of AGI on metals, as previously reported for AGI adsorbed on SCAu.23 Figure 6 shows the SERS spectra of AGI on SCAg and TNAg substrates at different pH values. These spectra are shown in Figure 6 normalized to the water band at 3400 cm−1. At low pH, AGI does not seem to be adsorbed onto the surface as deduced from the absence of bands from the drug. In the case of SCAg colloid, the SERS spectrum at low pH is dominated by the bands corresponding to citrate (marked with an asterisk in Figure 6a). The variation of the intensity of the most intense AGI band at 1606 cm−1 is shown in Figure 7 along with the variation of plasmon absorption at 702 nm of aggregated NPs at different pH, all of them normalized to their respective maximum value. From the pH dependence it can be deduced that the adsorption of AGI on Ag is only possible after deprotonation of the amino group in the AN moiety of the protonated drug (AGIH+). Therefore, the adsorption of AGI on Ag only takes place under the neutral form (AGI), in contrast to what it was observed for SCAu colloid, for which a more intense SERS spectra was observed at acidic pH.23 In Figure 7, a shift can be observed between the SERS/pH dependence curve with respect to the plasmon/pH one. The aggregation, and consequently the plasmon resonance, depends on the interfacial charge, which in turn is modified by the adsorption of neutral AGI. Thus, the variation of the plasmon resonance is actually associated with the drug dissociation leading to the pK value of 8 reported above in the following equilibrium:
Figure 5. SERS spectra of AGI at pH 6.0 on the following substrates and concentrations: (a) SCAg ([AGI] = 10−6 M) (asterisks indicate bands from citrate); (b) TNAg ([AGI] = 10−6 M); (c) SHAg ([AGI] = 10−4 M); (d) SCAu ([AGI] = 10−6 M); and (e) SBAg ([AGI] = 10−4 M). Spectrum (f) is the Raman spectrum of AGI in ethanol (0.5 M).
The interaction mechanism of AGI depends on the substrate. On TNAg and SHAg (Figure 5b,c), a higher contribution of GI bands is seen, while lower AN bands at 1239 and 647 cm−1 are observed. By contrast, on SCAg, stronger GI bands are seen at 1702 (νCO), 1302 (tCH2), 835, and 801 cm−1 (ρCH2) The differences observed on the latter substrate can be attributed to the large amount of citrate ions adsorbed on the surface at pH 6.0, which are responsible for the intense bands of this anion (marked with asterisks in Figure 5a). In addition, strong bands corresponding to Ag−Cl− and Ag−Br− are observed in SHAg and TNAg colloid (not shown in the Figure), indicating the existence of a large amount of halides on Ag. The presence of halides in TNAg seems to remove the larger amount of citrate and borohydride employed in its fabrication, since bromide is more strongly adsorbed on the silver surface. Therefore, the presence of other adsorbed species onto the surface seems to influence to a large extent the adsorption and the detection of AGI on the probed surfaces. By contrast, on a Au surface, a relatively strong interaction of AGI through the amino group of the AN moiety can be deduced from the appearance of intense bands at 1606, 1190, and 1077 cm−1, assigned to CC stretching, C−H in-plane bending, and NH2 rocking (Figure 5d). On Au, the adsorption is modulated by the protonation state of the AN amino group. While at low pH values the interaction mechanism of AGI with Au seems to take place through the aromatic AN protonated NH3+ (Figure 1b), at high pH the interaction could take place through a metal coordination bond involving the GI imide group. Enhancement Factors. Accordingly, the above results indicate that interaction of AGI with metals, and therefore its
AGIH+ + H2O ⇄ AGI + H3O+
pK = 8
By contrast, the SERS/pH is rather related to the adsorption mechanism and the surface coverage. Taking into account the above pK, the actual amount of AGI can be calculated at any pH value from the expression pK = pH + log([AGIH+]/ [AGI]), and also considering the mass balance [AGIH+] + [AGI] = 10−4 M. Thus, at pH = 6.0, the concentration of the neutral form ([AGI]) is ca. 10−6 M, while at pH = 7.0, [AGI] = 8895
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Table 2. Main Raman Bands and Assignment of AGI in Solid, Ethanolic Solution, and SERS on SCAu (pH = 4.0), SCAg (pH = 9.0) at High and Low Concentrations, and TNAg (pH = 9.0) at Low Concentration Raman solid
Raman EtOH
SERS SCAu
SERS SCAg 10−7 M
SERS SCAg 3 × 10−5 M
SERS TNAg 3 × 10−5 M
3379w
3059m 3017m 2970s 2947s 2914vs 2881m 1707s 1682w 1620s 1516w
1611vs 1513w
1458w 1439w 1414w
1455w 1433w 1410w
2936m
1292w
1225w 1201w 1190w 1153w 1078m
2936s
2933s
2876m
2880m
1607vs 1509w
1607vs 1516w
1606vs
1607vs 1510w
1491m 1454s
1450w
1405w
1294w
1381m 1335sh 1306vs
1330s
1219w
1213vw
1190m
1190m
1150vs 1078m
1147m 1080m
947s
1305w 1253w
1233m
1188w 1147w
1189m
1192m 1150w
1075m AN
1076vs
1062w
1049w
835s 801m
3065w
1714s
1380m
1294w
3064m 3013w
1012m
834s
888m 833m 798w
654m
835m
837m
950w 893w 833m
664m
746w 663w
732vw 666w
643w 633m
642w
622w 598w
596w
596vw
647vs 642m
579w 526w
640s
587m
assignmentsa
AGI group
νs(NH2)
AN
νar(CH)
AN
νas(CH3) νs(CH2) νs(CH2) νs (CH3) ν(CO) νas(CO) ν(CC) δ(NH) ν(CN)ν(CO) δ(CH2) δ(CH2) δ(CH2) δ(CH3) ν(CN) ν(CN) ω(CH2)/ν(C−NH2) t(CH2) δip(CH)/νar(C−NH2) t(CH) δip(CH) δ(CH)/ν(C−NH δip(CH)/t(CH2) ν(C−O)/t(CH2) ρ(NH2)/δip(CH)
GI GI GI GI GI GI AN GI Ag−GI GI GI GI GI Ag−GI Ag−GI AN/GI GI AN GI AN AN AN/GI Ag−GI
ν(CC)/ρ(CH3) δ(CNC)/ρ(CH3)
GI Ag−GI
δ(CCN)/ρ(CH2)
GI
ρ(CH2) δ(CNC) δar(CCN)/δar(CNH) δar(CNC) δ(N−CO)
GI GI AN AN GI
δop(CCC) δ(CO)
AN GI
a Symbols: ν, stretching; δ, bending; ρ, rocking; ω wagging; t, twisting; s, symmetric; as, asymmetric; ip, in-plane; op, out-of-plane; ar, aromatic; AN, anilinic, GI, glutarimide; Ag−GI, complex of GI group with Ag atoms.
10−5 M. On the other hand, the concentration at which the metal surface reaches a total coverage can be deduced by taking into account the total available surface (TAS) of Table 1 and the area per molecule, which was calculated to be 52 Å2. This concentration turned out to be (3.9 ± 0.8) μM for SCAg and (1.82 ± 0.38) μM for TNAg. Therefore, the surface saturation by the AGI adsorption is expected to occur at pH between 6.0 and 7.0. This is then the reason to observe a saturation of the SERS signal above a pH of 7.0, even if the desprotonation of AGIH+ is not yet completed. The pH not only modifies the SERS intensity but also the SERS profile of AGI on Ag surfaces (Figure 6). Above a pH of
9.0, stronger bands of GI moiety can be seen at 2936, 1454, 1150, 837, and 663 cm−1 (Table 2) in relation to the AN band at 1606 cm−1. Thus, although two different interactions can occur on the Ag surface (with interactions through both AN and GI groups), an increasing importance of the interaction through the GI moiety can be deduced at higher pH. The change observed at pH 9.0 can be attributed to different reasons: (a) deprotonation of the imide NH group of neutral AGI thus leading to a stronger interaction through the N atom of imide moiety, as depicted in Figure 1c, or (b) reorientation of the molecule induced by the adsorbate concentration variation governed by the acid−base equilibrium shown 8896
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the amount of neutral AGI. In order to monitor this effect, SERS spectra of the drug were also measured at different concentration on both SCAg and TNAg colloids. TAS values per mL are shown in Table 1 for all the analyzed metallic substrates. As the surface coverage effect is strongest on SCAg, we only show the SERS spectra of AGI at different drug concentration on these NPs (Figure 8). These spectra show
Figure 6. SERS spectra of AGI (10−4 M) on SCAg and on TNAg at different pH.
Figure 8. Bottom: SERS spectra of AGI at different drug concentration fixing the pH to 9.0. Top: Plot of the I1150/ I1190 ratio against AGI concentration and reorientation from bidentate (B) to monodentate (M) interaction with the metal deduced from the spectra and concentrations at which this reorientation occurs ([B] = [M]).
two different profiles undergoing a transition in the 1−3 μM range of concentration. Below this threshold, the adsorption seems to take place through a simultaneous interaction with both AN and GI moieties, but at higher concentrations the role of the GI group in the adsorption is greater, as deduced from the relative intensification of bands attributed to this part of the molecule (2936 cm−1, attributed to νC−H; 1454 cm−1, due to δCH2 and δCH3; 947 cm−1, due to νC−C stretching; 837 and 663 cm−1, attributed to GI deformations; see Table 2). This result suggests that at low surface coverage a bidentate adsorption (B) of AGI through both the AN and GI binding sites seems to occur (top inset in Figure 8), while at higher surface coverage a monodentate (M) interaction of AGI through GI will be favored. To better evaluate this effect, the I1150/I1190 ratio was plotted against the AGI concentration obtaining a sigmoidal plot with concentration transitions ([AGI]t) occurring at 1.75 μM and 1.38 μM in the case of SCAg and TNAg, respectively (Top figure in Figure 8). [AGI]t represents the concentration at which [B] = [M], while at [AGI] = 5 μM the drug is expected to be totally adsorbed under a monodentate configuration on both surfaces ([M] ≫ [B]). Assuming that the TAS on SCAg and TNAg is 12.3 and 6.04 cm2/mL, respectively (Table 1), and that [AGI]t corresponds
Figure 7. Variation of the intensity of AGI (10−4 M) SERS band at 1606 cm−1 on SCAg (circles) and on TNAg (open circles) on varying the pH, and variation of the plasmon band at 702 nm also at different pH (triangles). All these intensities were normalized to their maximum values.
above. The deprotonation of the imide N−H group occurs at pH 11.8 in glutethimide,43 but this pK could be very much lowered in the presence of Ag due to the formation of a Ag−GI complex.44 However the absence of CO bands at any pH suggests that the deprotonation already occurs at pH lower than 9.0. Therefore, the only factor that accounts for such a change is a reorientation. On TNAg NPs, the increase of GI bands detected on this substrate is lower (Figure 6, bottom spectra). This can be attributed to the higher adsorption restrictions existing on their surfaces (see below). Effect of Surface Coverage. From the SERS/pH dependence, a clear influence of the surface coverage and TAS on the adsorption of AGI was deduced, since the pH actually modifies 8897
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to 1.1 × 1015 and 8.0 × 1014 molecules/mL, the calculated area per molecule onto these surfaces at their maximum coverage is 1.12 and 0.75 nm2. These values are slightly higher than the theoretical area calculated for AGI, which is 52 Å2 (0.52 nm2) assuming a flat orientation onto the surface. This small disagreement is attributed to the presence of other species also adsorbed on the Ag surface (citrate and bromide), which avoids a full coverage of the metal surface. Although a similar saturation concentration was found for TNAg, the lower I1150/I1190 ratio reached at conditions of saturation (1.85) in this case suggests that this reorientation could not be complete on this substrate. This is attributed to the presence of Br− ions on the latter surface, which seems to weaken the Ag-imide strength by limiting the Lewis acidic character of interfacial Ag+ ions. Bromide seems to induce a relative passivation of the metallic surface in relation to their interaction with adsorbates, likely due to a partial charge transfer from the anion to the metal,45 which in turns induces an increase of the surface electric potential.40 Since the monodentate adsorption involves a strong interaction through the N atom of the GI moiety, in addition to the relative intensification of the SERS bands corresponding to this moiety, a modification of the imide bands is expected. This is the case of the broad band at 1350−1300 cm−1, and the strong band appearing at 1150 cm−1, which are assigned to the new ν(C:::N) and ν(C:::O) vibrations resulting from the formation of a strong Ag−N bond inducing a higher electronic delocalization in the imide group (Table 2). This strong interaction is also supported by the appearance of a new band at 214 cm−1 (not shown here) attributed to Ag−N stretching.46 Furthermore, the monodentate adsorption implies a more perpendicular orientation of the AN ring, which is supported by the relative intensification of the in-plane C−H stretching of the benzene ring at 3064 cm−1. Adsorption Isotherms and Detection of AGI. According to the results shown in the above section, the AGI adsorption on Ag is larger at high pH. This behavior is opposite to that followed by AGI on Au, where the SERS is stronger at acidic pH.23 Therefore, the detection study of AGI was made by using SCAg and TNAg substrates and fixing the pH at 9.0. Additionally, the CC stretching band at 1606 cm −1 (normalized to that of water) was chosen as the AGI marker band because it is the most intense and well-resolved band in the spectrum. Figure 9 shows the SERS intensity variation of the marker band against the drug concentration on both SCAg and TNAg colloids. The resulting plots follow a simple adsorption− saturation Langmuir curve in both cases, thus indicating that there is no significant intermolecular interaction between AGI molecules on the surface. The general expression of a Langmuir adsorption can be expressed by the following equation: ϕ /ϕ∞ =
Kad[A] 1 + Kad[A]
Figure 9. Adsorption isotherms obtained from the variation of the relative intensity of the AGI SERS band at 1606 cm−1 on SCAg (circles) and on TNAg (open circles) on varying the drug concentration.
intensity in conditions of saturation, i.e., at maximum surface coverage). Therefore, to fit the SERS intensity versus the drug concentration in the sample, a Langmuir-type function can be used in the following form: Is =
KadIsm[AGI] 1 + Kad[AGI]
(2)
From the Is versus [AGI] plot, the adsorption parameters can be deduced (Table 3). In general, a high affinity of AGI toward Table 3. Adsorption Parameters and Limits of Detection Calculated from the Langmuir Fittings for the SERS of AG on SCAu, SCAg, and TNAg parameter
SCAu
SCAg
TNAg
Kads × 10−7 (L·mol−1) Ism [AGI]max (μM) R2 LOD (ng·mL−1, ppb)
2.5 ± 1.1 6.0−9.0 0.9994 85
7.2 ± 0.1 1.72 ± 0.07 6.0 0.991 5.1
150 ± 20 0.350 ± 0.006 1.0−3.0 0.994 0.13 (130 ppt)
all the monitored metallic surfaces was found, as deduced from the high Kad values. The latter constant should be the same on all the Ag substrates, but the higher Kad deduced on TNAg in comparison to SCAg is rather attributed to an apparent effect derived from the higher intensification of the electromagnetic field in TNAg corners and interparticle junctions where hot spots are formed, at low surface coverage. Therefore we can consider that (Kad)TNAg = p*(Kad)SCAg, where p is a factor related to the plasmonic advantages of TNAg NPs in comparison to SCAg. The p factor turned out to be 20.8 in the case of TNAg. Furthermore, the highest affinity found on Ag surfaces in relation to Au, is likely due to the fact that the adsorption study on the latter metal was accomplished at pH = 4.0, since at this pH a weaker ionic AGIH+/Au interaction was deduced, although a plasmonic effect to this fact is not discarded. From Figure 9, the AGI concentration at which the saturation in the SERS intensity occurs can be deduced ([AGI]max), being 1.0−3.0 μM and 6.0 μM for TNAg and SCAg, respectively. These values correlate very well with the AGI concentration at which the reorientation on the surface is completed due to a full surface coverage on the surface (5 μM,
(1)
Where Kad is the adsorption constant of the adsorbate (A) on the Au surface, ϕ is the amount of adsorbed molecules at a concentration [A], and ϕ∞ is the maximum number of molecules which can be adsorbed on the surface. Since the SERS intensity exclusively depends on the number of molecules adsorbed on a plasmonic surface, the ϕ/ϕ∞ ratio can be approximated to the SERS intensity ratio Is/Ism (where Is is the SERS intensity at concentration [A], and Ism is the SERS 8898
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standard deviation of the intensities) of this method are better for TNAg NPs than for SCAg ones. The higher sensitivity observed at low concentrations of TNAg NPs is attributed to the better morphological properties of the nanoprisms, which render a higher SERS signal due to the adsorption of AGI in interparticle spaces at submonolayer coverage. Nevertheless, at full surface coverage the SERS efficiency, in terms of total amount of adsorbed drug, of the latter surfaces is seriously limited by the presence of bromide, which in turn is necessary to obtain this special geometry by this particular synthesis method. This means that the detection properties of TNAg could be improved by increasing the TAS, e.g., eliminating bromide ions from their surface or concentrating the number of NPs, without an increase of the colloidal instability. In a future work we will try to improve these properties by immobilizing these nanoprisms and by removing halide ions from their surface.
Figure 6). Moreover, this value also agrees with the theoretical concentration at maximum coverage, deduced by dividing the TAS of each colloid by the estimated area per molecule at a monodentate orientation (0.30 nm2), which resulted to be 3.15 and 6.75 μM for TNAg and SCAg, respectively. The lower value of [AGI]max for TNAg is indeed related to the lower available surface, which is further limited by the presence of adsorbed bromide ions, which are not desorbed by OH− ions,40 while in SCAg the citrate ions are completely detached at pH 9.0. The maximum relative SERS intensity (Ism) is indeed related to [AGI]max. The higher value of Ism observed on SCAg surface in comparison to TNAg (ca. 4 times higher) indicates that these NPs can hold a greater amount of molecules, not only because of the higher TAS value (Table 1), which is 2 times greater, but also because of the presence of bromide ions on the surface of the triangular nanoprisms, which seriously limits the total surface coverage. At very low AGI concentrations, i.e., when Kad[A] ≪ 1, eq 2 becomes linear: IS = KadIsm[A], and a calibration line can be then built (Figure 10a,b). The concentration range at which
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CONCLUSIONS The detection of AGI by SERS was possible at concentrations as low as 130 ppt by using plasmonic metal NPs. Triangular nanoprisms turned out to be the most active substrate in comparison to other usually employed systems such as spherical NPs of Ag and Au prepared by reduction with citrate, borohydride, or hydroxylamine. The SERS activity of all these systems depends on the adsorption of AGI onto the surface to benefit from the high intensification of the near-field electromagnetic field by localization of surface plasmon. Therefore, a previous study of this adsorption was very important to understand the interfacial behavior of the analyte onto the metallic surface. This adsorption was found to depend on factors such as (a) the aff inity toward the metal, (b) the adsorbate charge, which is modulated by the pH; (c) the surface coverage; and (d) the presence of residual ions on the surface remaining from the nanofabrication process. All these variables must be considered to optimize the application of SERS in chemical sensing. The pK of AGI was calculated for the first time here from the data afforded by the plasmon resonance spectra at different pH. The adsorption isotherms of AGI on spherical and triangular nanoprism NPs followed a Langmuir-type mechanism, thus indicating that there is no significant intermolecular interaction between AGI molecules on the surface. From these isotherms, the main adsorption parameters could be obtained (Kad, Ism, and [AGI]max). The existence of two binding sites in AGI also determines two possible interaction mechanisms on Ag: bidentate and monodentate, with a bi-to-monodentate transition occurring at high pH and at high surface coverage. Additionally, this transition takes place at AGI concentration values at which a maximum coverage is expected taking into account the total available adsorption surface of the colloidal suspension. TNAg colloid exhibits several advantages in relation to the other metallic colloids. The Kad of AGI to bind TNAg colloid is the highest, although this is an apparent effect determined by the better morphological properties of nanoprisms inducing a strong intensification of the electromagnetic field in corners and interparticle junctions, where hot spots are formed. In addition, the sensitivity, LOD, and reproducibility are better for TNAg NPs than for SCAg ones. However, the SERS efficiency of TNAg NPs is seriously limited by their interfacial characteristics, since the presence of bromide avoids a bigger SERS intensification by limiting the TAS. Additionally, another
Figure 10. Details of the variation of the relative intensity of the AGI SERS band at 1606 cm−1 on SCAg (circles) and on TNAg (open circles) at different drug concentrations in the [AGI] range at which a linear dependence occurs: 10−8−10−7 M (a) and 10−9−10−8 M (b), which in turns correspond to 2.0−20 and 0.2−2.0 ppb (200−2000 ppt) intervals for SCAg and TNAg, respectively.
this linearity occurs is 10−8−10−7 M (Figure 10a) for SCAg and 10−9−10−8 M (Figure 10b) for TNAg. The LODs deduced for both substrates are 5.1 and 0.13 ppb, respectively, which is the lowest reported so far for the detection of this drug. Comparatively, the sensitivity (estimated by the slope of the calibration curve) and reproducibility (estimated by the 8899
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(10) Wiley, B. J.; Xiong, Y.; Li, Z. Y.; Yin, Y.; Xia, Y. N. Right bipiramids of silver: A new shape derived from twin seeds. Nano Lett. 2006, 6, 765−768. (11) Aroca, R. F.; Alvarez-Puebla, R. A.; Pieczonka, N.; SanchezCortez, S.; Garcia-Ramos, J. V. Surface-enhanced Raman scattering on colloidal nanostructures. Adv. Colloid Interface Sci. 2005, 116, 45−61. (12) Pastoriza-Santos, I.; Alvarez-Puebla, R. A.; Liz-Marzan, L. M. Synthetic routes and plasmonic properties of noble metal nanoplates. Eur. J. Inorg. Chem. 2010, 4288−4297. (13) Jin, R. C.; Cao, Y. W.; Mirkin, C. A.; Kelly, K. L.; Schatz, G. C.; Zheng, J. G. Photoinduced conversion of silver nanospheres to nanoprisms. Science 2001, 294, 1901−1903. (14) An, J.; Tang, B.; Ning, X. H.; Zhou, J.; Xu, S. P.; Zhao, S.; Xu, W. Q.; Corredor, C.; Lombardi, J. R. Photoinduced shape evolution: From triangular nanoprisims to hexagonal nanoplates. J. Phys. Chem. C 2007, 111, 18055−18059. (15) Sato-Berru, R.; Redon, R.; Vaquez-Olmos, A.; Saniger, J. M. Silver nanoparticles synthesized by direct photoreduction of metal salts. Application in surface-enhanced Raman spectroscopy. J. Raman Spectrosc. 2009, 40, 376−380. (16) Cathcart, N.; Frank, A. J.; Kitaev, V. Silver nanoparticles with planar twinned defects: Effect of halides for precise tuning of plasmon resonance maxima from 400 to >900 nm. Chem. Commun. 2009, 7170−7172. (17) Zhang, J. H.; Liu, H. Y.; Zhan, P.; Wang, Z. L.; Ming, N. B. Controlling the growth and assembly of silver nanoprisms. Adv. Funct. Mater. 2007, 17, 1558−1566. (18) Metraux, G. S.; Mirkin, C. A. Rapid thermal synthesis of silver nanoprisms with chemically tailorable thickness. Adv. Mater. 2005, 17, 412. (19) Sun, Y. G.; Xia, Y. N. Triangular nanoplates of silver: Synthesis, characterization and use as sacrificial templates for generating triangular nanorings of gold. Adv. Mater. 2003, 15, 695−699. (20) Tiwari, V. S.; Oleg, T.; Darbha, G. K.; Hardy, W.; Singh, J. P.; Ray, P. C. Non-resonance: SERS effects of silver colloids with different shapes. Chem. Phys. Lett. 2007, 446, 77−82. (21) Gale, K. E.; Andersen, J. W.; Tormey, D. C.; Mansour, E. G.; Davis, T. E.; Horton, J.; Wolter, J. M.; Smith, T. J.; Cummings, F. J. Hormonal treatment for metastatic breast-cancer - An Eastern Cooperative Oncology Group-Phase III- trial comparing aminoglutethimide to tamoxifen. Cancer 1994, 73, 354−361. (22) World Anti-Doping Agency. The 2011 Prohibited List International Standard; WADA: Montreal, Canada, 2011. (23) Izquierdo-Lorenzo, I.; Sanchez-Cortes, S.; Garcia-Ramos, J. V. Trace detection of aminoglutethimide drug by surface-enhanced Raman spectroscopy: A vibrational and adsorption study on gold nanoparticles. Anal. Methods 2011, 3, 1540−1545. (24) Izquierdo-Lorenzo, I.; Sanchez-Cortes, S.; Garcia-Ramos, J. V. Adsorption of beta-adrenergic agonists used in sport doping on metal nanoparticles: A detection study based on surface-enhanced Raman scattering. Langmuir 2010, 26, 14663−14670. (25) Mareck, U.; Sigmund, G.; Opfermann, G.; Geyer, H.; Schanzer, W. Identification of the aromatase inhibitor aminoglutethimide in urine by gas chromatography/mass spectrometry. Rapid Commun. Mass Spectrom. 2002, 16, 2209−2214. (26) Kang, M. J.; Hwang, Y. H.; Lee, W.; Kim, D. H. Validation and application of a screening method for beta 2-agonists, anti-estrogenic substances and mesocarb in human urine using liquid chromatography/tandem mass spectrometry. Rapid Commun. Mass Spectrom. 2007, 21, 252−264. (27) Abdelkhalek, M. M.; Mahrous, M. S.; Daabees, H. G.; Beltagy, Y. A. Spectrophotometric determination of aminoglutethimide by diazotization and subsequent coupling. Anal. Lett. 1993, 26, 1109− 1123. (28) Poon, G. K.; Bisset, G. M. F.; Mistry, P. Electrospray-ionization mass-spectrometry for analysis of low-molecular-weight anticancer drugs and their analogs. J. Am. Soc. Mass Spectrom. 1993, 4, 588−595. (29) Aboul-Enein, H. Y.; Ozkirimli, S.; Apak, T. I. Determination of aminoglutethimide enantiomers as dansyl derivative in human plasma
effect of the halide is a strong electron donating effect toward the metal, which decreases the AGI−Ag interaction and prevents a total reorientation of the drug at high concentrations. Even so, the LOD deduced in this work is the lowest ever measured for this drug, thus demonstrating the high efficiency of SERS in ultrasensitive detection of doping drugs.
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ASSOCIATED CONTENT
S Supporting Information *
Additional experimental data on the effect of pH on the extinction spectrum of different colloids, as well as detailed explanations concerning the influence of the excitation line on the enhancement factor and the method employed for the enhancement factor estimations are included as Supporting Information. This information is available free of charge via the Internet at http://pubs.acs.org/.
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AUTHOR INFORMATION
Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS This work has been supported by the Spanish Ministerio de Ciencia e Innovación (Grant FIS2010-15405) and Comunidad de Madrid through the MICROSERES II network (grant S2009/TIC-1476). I.I.-L. acknowledges CSIC and FSE 20072013 for a JAE-CSIC predoctoral grant. The Biophysics of Macromolecular Systems Group of IEM-CSIC is acknowledged for the TEM measurements.
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REFERENCES
(1) Nafie, L. A. Recent advances in linear and nonlinear Raman spectroscopy. Part IV. J. Raman Spectrosc. 2011, 41, 1276−1296. (2) Aroca, R. Surface-Enhanced Vibrational Spectroscopy; John Wiley & Sons: Chichester, U.K., 2006. (3) Guerrini, L.; Garcia-Ramos, J. V.; Domingo, C.; Sanchez-Cortes, S. Nanosensors based on viologen functionalized silver nanoparticies: Few molecules surface. Enhanced Raman spectroscopy detection of polycyclic aromatic hydrocarbons in interparticle hot spots. Anal. Chem. 2009, 81, 1418−1425. (4) Trachta, G.; Schwarze, B.; Sagmuller, B.; Brehm, G.; Schneider, S. Combination of high-performance liquid chromatography and SERS detection applied to the analysis of drugs in human blood and urine. J. Mol. Struct. 2004, 693, 175−185. (5) Guerrini, L.; Izquierdo-Lorenzo, I.; Garcia-Ramos, J. V.; Domingo, C.; Sanchez-Cortes, S. Self-assembly of α,ω aliphatic diamines on Ag nanoparticles as an effective localized surface plasmon nanosensor based in interparticle hot spots. Phys. Chem. Chem. Phys. 2009, 11, 7363−7371. (6) Graham, D. The next generation of advanced spectroscopy: Surface enhanced Raman scattering from metal nanoparticles. Angew. Chem., Int. Ed. 2010, 49, 9325−9327. (7) Guerrini, L.; Leyton, P.; Campos-Vallette, M.; Domingo, C.; Garcia-Ramos, J. V.; Sanchez-Cortes, S. Detection of Persistent Organic Pollutants by Using SERS Sensors Based on Organically Functionalized Ag Nanoparticles. In Surface Enhanced Raman Spectroscopy; Schlücker, S., Ed.; Wiley-VCH: Weinheim, Germany, 2010; pp 103−128. (8) Lu, X. M.; Rycenga, M.; Skrabalak, S. E.; Wiley, B. J.; Xia, Y. N. Chemical synthesis of novel plasmonic nanoparticles. Annu. Rev. Phys. Chem. 2009, 60, 167−192. (9) Kim, J. H.; Kang, T.; Yoo, S. M.; Lee, S. Y.; Kim, B.; Choi, Y. K. A well-ordered flower-like gold nanostructure for integrated sensors via surface-enhanced Raman scattering. Nanotechnology 2009, 20, 235302. 8900
dx.doi.org/10.1021/la300194v | Langmuir 2012, 28, 8891−8901
Langmuir
Article
by HPLC with fluorescence detection. Arch. Pharm. 1999, 332, 145− 147. (30) Cesur, N.; Apak, T. I.; Aboul-Enein, H. Y.; Ozkirimli, S. LC determination of amino glutethimide enantiomers as dansyl and fluorescamine derivatives in tablet formulations. J. Pharm. Biomed. 2002, 28, 487−492. (31) Elbashir, A. A.; Suliman, F. E. O.; Saad, B.; Aboul-Enein, H. Y. Determination of aminoglutethimide enantiomers in pharmaceutical formulations by capillary electrophoresis unsing methilated betacyclodextrin as chiral selector and computational calculation for their respective inclusion process. Talanta 2009, 77, 1338−1393. (32) Sutherland, W. S.; Winefordner, J. D. Colloid filtration: A novel substrate preparation method for surface-enhanced Raman spectroscopy. J. Colloid Interface Sci. 1992, 148, 129−141. (33) Cañamares, M. V.; Garcia-Ramos, J. V.; Gomez-Varga, J. D.; Domingo, C.; Sanchez-Cortes, S. Comparative study of the morphology, aggregation, adherence to glass, and surface-enhanced Raman scattering activity of silver nanoparticles prepared by chemical reduction of Ag+ using citrate and hydroxylamine. Langmuir 2005, 21, 8546−8553. (34) Leopold, N.; Lendl, B. A new method for fast preparation of highly surface-enhanced Raman scattering (SERS) active silver colloids at room temperature by reduction of silver nitrate with hydroxilamine hydrochloride. J. Phys. Chem. B 2003, 107, 5723−5727. (35) Sanchez-Cortes, S.; Garcia-Ramos, J. V.; Morcillo, G. Morphological-study of metal colloids employed as substrate in the SERS spectroscopy. J. Colloid Interface Sci. 1994, 167, 428−436. (36) Cañamares, M. V.; Garcia-Ramos, J. V.; Sanchez-Cortes, S.; Castillejo, M.; Oujja, M. Comparative SERS effectiveness of silver nanoparticles prepared by different methods: A study of the enhancement factor and the interfacial properties. J. Colloid Interface Sci. 2008, 326, 103−109. (37) Sanchez-Cortes, S.; Garcia-Ramos, J. V.; Morcillo, G. In Morphological Study of Metal Colloids Employed as Substrate in SERS spectroscopy, 14th International Conference on Raman Spectroscopy, Hong Kong, Hong Kong, Aug 22−26, 1994; Yu, N. T., Li, X. Y., Eds.; Wiley: New York, 1994; pp 664−665. (38) Sanchez-Cortes, S.; Garcia-Ramos, J. V.; Morcillo, G.; Tinti, A. Morphological-study of silver colloids employed in surface-enhanced Raman-spectroscopy - Activation when exciting in visible and nearinfrared regions. J. Colloid Interface Sci. 1995, 175, 358−368. (39) Chen, S.; Carroll, D. L. Synthesis and characterization of truncated triangular silver nanoplates. Nano Lett. 2002, 2, 1003−1007. (40) Sibbald, M. S.; Chumanov, G.; Cotton, T. M. Reduction of cytochrome c by halide-modified, laser-ablated silver colloids. J. Phys. Chem. 1996, 100, 4672−4678. (41) Ciou, S. H.; Cao, Y. W.; Huang, H. C.; Su, D. Y.; Huang, C. L. SERS enhancement factors studies of silver nanoprism and spherical nanoparticle colloids in the presence of bromide ions. J. Phys. Chem. C 2009, 113, 9520−9525. (42) Emory, S. R.; Haskins, W. E.; Nie, S. M. Direct observation of size-dependent optical enhancement in single metal nanoparticles. J. Am. Chem. Soc. 1998, 120, 8009−8010. (43) Deluca, P. P.; Lachman, L.; Schroeder, H. G. Physical-chemical properties of substituted amides in aqueous-solution and evaluation of their potential use as solubilizing agents. J. Pharm. Sci. 1973, 62, 1320− 1327. (44) Morzyk-Ociepa, B.; Michalska, D. FT-Raman and infrared spectra of silver(I) complexes with glutarimidate and 3,3-dimethylglutarimidate anions. Spectrochim. Acta A 1999, 55, 2671−2676. (45) Marichev, V. A. First experimental evaluation of partial charge transfer during anion adsorption. Colloid Surf., A 2009, 348, 28−34. (46) Rivas, L.; Murza, A.; Sanchez-Cortes, S.; Garcia-Ramos, J. V. Adsorption of acridine drugs on silver: Surface-enhanced resonance Raman evidence of the existence of different adsorption sites. Vib. Spectrosc. 2001, 25, 19−28.
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