IR, Raman and SERS analysis of amikacin combined with DFT-based calculations

Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 214 (2019) 79–85

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Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy journal homepage: www.elsevier.com/locate/saa

IR, Raman and SERS analysis of amikacin combined with DFT-based calculations Cristina Balan a,1, Lucian-Cristian Pop b,c,1, Monica Baia a,c,⁎ a b c

Faculty of Physics, Babeş-Bolyai University, Mihail Kogalniceanu 1, 400084 Cluj-Napoca, Romania Faculty of Chemistry and Chemical Engineering, Babeş-Bolyai University, Arany János 11, 400028 Cluj-Napoca, Romania Institute for Interdisciplinary Research in Bio-Nano-Sciences, Babeş-Bolyai University, Treboniu Laurian 42, 400271 Cluj-Napoca, Romania

a r t i c l e

i n f o

Article history: Received 27 September 2018 Received in revised form 30 January 2019 Accepted 5 February 2019 Available online 6 February 2019 Keywords: Amikacin Antibiotics IR Raman SERS DFT

a b s t r a c t Amikacin, a molecule formed by two glucosamine rings linked by α-linkages through a central deoxystreptamine, is an antibiotic often used in clinical treatments, with a special attention in the pediatric cases, due to the physiological activity of their renal system. In spite of its extensive use, no detailed information about the vibrational features of the molecule is available in the literature. Thus, in this study we performed a comprehensive vibrational investigation of amikacin from both an experimental and theoretical point of view. Raman and IR spectroscopy combined with DFT calculations conducted to a complete vibrational characterization of the molecule, with the assignment of the vibrational modes. Moreover, SERS spectrum was recorded and analyzed and provided information about the adsorption behavior of the amikacin on the silver nanoparticles surface. © 2019 Elsevier B.V. All rights reserved.

1. Introduction Nowadays, the research related to antibiotics and their resistance is a major subject in medical areas, as a proof stands the trend of the current medical publications [1–3]. Due to the clinical importance and the lack of vibrational investigations in the literature, amikacin was chosen to be characterized in this study. With the chemical formula C22H43N5O13, the molecule is formed by two glucosamine rings linked by α-linkages through a central deoxystreptamine (see Fig. 1) [4]. This water-soluble, semisynthetic antibiotic from the class of aminoglycosides, is used in the treatment of the several infections produce by Gram-negative bacteria [5]. Amikacin is considered an important bactericidal drug when the treatment is addressed to pediatric patients with severe infections, so the dosage in these situations becomes a major responsibility for the clinicians. Amikacin is excreted by the renal system, through glomerular filtration, and therefore, an inadequate dosage can cause nephrotoxicity and ototoxicity [6–11]. Since specific studies about drugs and not only, should create a comprehensive representation of the structural information about their molecule because there is a relation between the drugs structure and their properties, the use of the spectroscopic methods combined with density functional theory (DFT) based calculations represents an accurate way ⁎ Corresponding author at: Faculty of Physics, Babeş-Bolyai University, Mihail Kogalniceanu 1, 400084 Cluj-Napoca, Romania. E-mail address: [email protected] (M. Baia). 1 These authors contributed equally to this work.

https://doi.org/10.1016/j.saa.2019.02.012 1386-1425/© 2019 Elsevier B.V. All rights reserved.

for this purpose [12–15]. By reading the literature we found that there are some structural studies of antibiotics, which combine the theoretical approach with the experimental one [16,17], but the molecule of amikacin was not yet studied. The Raman spectrum of amikacin is not reported in the literature, instead the FT-IR spectrum of the molecule was recorded in a previous study [18]. Vibrational spectroscopy is an analytical method frequently used for pharmaceuticals investigations [19–22], so in this study Raman, IR and surface-enhanced Raman spectroscopy (SERS), combined with DFT calculations were used to characterize the amikacin molecule. To understand a molecule and its behavior in different types of interactions is necessary to have an overview of its chemical and physical properties, thus the experimental and theoretical methods work together for a comprehensive analysis of amikacin. The aim of this comparative study is to describe the amikacin molecule by its vibrational characteristics from two perspectives: the experimental one, by means of Raman and IR spectroscopy, and the theoretical approach by using molecular computational methods, as DFT. SERS spectroscopy was also used for elucidating the adsorption behavior of amikacin on the surface of metal nanoparticles, a process that mimics the adsorption of the drugs that occurs into the organism. 2. Experimental details 2.1. Materials and methods Amikacin of 99% purity was purchased from Cayman Chemical Company and all other materials involved in substrate and solutions

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glucosamine ring

deoxystreptamine ring

glucosamine ring

Fig. 1. Chemical structure of the amikacin and the optimized geometry of the model compound obtained at the BPW91/6-31+G* theoretical level with the legend of the atoms.

preparation were purchased from Sigma Aldrich as analytical pure reagents. A stable sodium citrate silver colloid was prepared according to the standard procedure of Lee and Meisel [23] and employed as the SERS substrate. Thus, over 50 ml of 10−3 M AgNO3 at boiling temperature 0.8 ml solution of (38.8 mM) anhydrous trisodium citrate was added. After 5–7 min the colour of silver colloid stabilized at dark yellowish [23]. Having in mind that silicone grease, even though considered chemically inert, could take part in the reactions (e.g. reduction of the silver salt) its use was avoided for the entire duration of the experiments [24]. Different amounts of silver colloid, 10−2 M aqueous solution of amikacin and 10−1 M NaCl aqueous solution were mixed and stock solutions of different amikacin concentrations were obtained and used in order to record the best SERS spectrum. NaCl solution was added to produce a stabilization of the colloidal dispersion that results in a considerable enhancement of the SERS signal [25]. Thus, the final concentration of the amikacin in the colloidal suspension was of 10−3 M. The UV-VIS absorption spectra of silver colloid before and after addition of NaCl aqueous solution (10−1 M) and amikacin aqueous solution (10−2 M) were recorded by using an UV-VIS JASCO-V650 spectrometer. FT-IR absorption spectrum of amikacin was recorded with a JASCO 6200 spectrometer and a resolution of 4 cm−1, by using the KBr pellet technique, in the range of 400–4000 cm−1. The Raman spectra of both solid-state and 1 M aqueous solution of amikacin and the SERS spectra were recorded in backscattering geometry by using a multi-laser confocal Renishaw InVia Reflex Raman spectrometer equipped with an Leica 20× (NA 0.35) microscope objective, an 1800 lines/mm grating, and an external laser with an emission wavelength of 532 nm. In the recording of the SERS spectra, a power of 150 mW incident on the sample was employed. The spectral resolution was about 4 cm−1. The SERS spectra were recorded by focusing the laser beam on a 50 μl droplet deposited on a glass slide covered by parafilm.

2.2. Computational details The theoretical simulations in this comparative study, more exactly the molecular structure optimization and the calculation of the theoretical vibrational wavenumbers of the amikacin were performed with the Gaussian 03W package [26]. The DFT calculations were carried out with two functionals: Becke's 1988 exchange functional and the PerdewWang 91 gradient corrected correlation functional (BPW91) and Becke's three-parameter hybrid method using the Lee-Yang-Parr correlation functional (B3LYP), together with the same basis set 6-31+G* [27–29]. For the optimized structure of the amikacin molecule no imaginary frequency modes were obtained, which leads to the conclusion that the structure is a local minimum on the potential energy surface.

3. Results and discussion 3.1. IR and Raman measurements. DFT calculations Amikacin is formed by three significant units, two peripheral glucosamine rings and a central deoxystreptamine ring, as it can be seen in Fig. 1, where the optimized geometry of the molecule is illustrated together with the chemical structure [4]. The amikacin molecule has a very low symmetry, none of the its rings being planar. The geometry optimization, theoretical IR and Raman spectra were calculated within this two theory levels BPW91/6-31+G* and B3LYP/6-31+G*. Since the vibrational spectroscopy is strongly related to the structural characteristic of the molecule, Table 1 presents some selected internal coordinates of the optimized structure of amikacin obtained at both theory levels used in this study. For equivalent internal coordinates were cited the experimental values of the molecule of amikacin, which were obtained throughout an X-ray diffraction study [4]. Looking at the results, one

C. Balan et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 214 (2019) 79–85 Table 1 Selected bonds lengths (Å), bond angles and torsion angles (c) of the amikacin molecule. Theoretical values

Experimental values ref. [4]

BPW91

B3LYP

Bond lengths C1-O22 C17-C2 C17-O20 C2-C3 O13-C3 C3-C4 N10-C4 C5-C4 O15-C5 O23-C1 O23-C24 C25-C24 C26-C24 O35-C25 C27-C25 C27-C30 N39-C30 C28-C26 C26-N42 C68-N42 O82-C68 C69-C68 O80-C69 C69-C71 C71-C74 N77-C74 O37-C27 C44-O37 C44-C45 C45-O55 C45-C47 C47-O57 C47-C49 C49-O59 C46-C62 C62-N65 O61-C44

1.418 1.543 1.434 1.571 1.438 1.569 1.463 1.529 1.430 1.443 1.442 1.534 1.552 1.428 1.533 1.548 1.481 1.539 1.461 1.366 1.239 1.542 1.446 1.538 1.535 1.474 1.457 1.428 1.539 1.421 1.546 1.434 1.545 1.433 1.543 1.481 1.429

1.410 1.536 1.427 1.560 1.431 1.560 1.458 1.525 1.423 1.429 1.434 1.530 1.546 1.421 1.529 1.545 1.477 1.535 1.459 1.358 1.230 1.535 1.437 1.534 1.531 1.469 1.448 1.418 1.533 1.414 1.540 1.425 1.540 1.425 1.536 1.475 1.420

1.401 1.504 1.431 1.526 1.438 1.517 1.471 1.517 1.446 1.434 1.451 1.518 1.510 1.434 1.522 1.517 1.479 1.510 1.472 1.345 1.246 1.525 1.430 1.478 1.522 1.497 1.443 1.411 1.492 1.442 1.502 1.438 1.537 1.433 1.496 1.473 1.410

Bond angles C1-O22-C5 C2-C3-C4 C3-C4-C5 N10-C4-C3 C1-O23-C4 C28-C26-C24 O82-C68-N42 C69-C71-C74 C30-C27-C25 O35-C25-C24 N39-C30-C27 C27-O37-C44 C44-C45-C47 C47-C49-C45 C46-C62-N65

114.2 112.5 111.4 115.4 120.2 109.0 124.0 114.7 111.8 105.9 108.6 117.2 111.5 113.9 111.7

113.9 112.2 111.3 115.0 112.1 107.2 123.9 114.6 105.1 109.3 109.2 117.9 111.3 113.9 111.7

115.6 109.1 108.1 110.0 113.8 110.9 123.8 112.8 108.6 108.6 113.6 118.5 109.4 108.0 104.4

93.2 −143.7 149.1 179.3 −62.3 −0.9 179.5

93.1 −144.3 149.6 178.2 −63.1 −1.8 179.1

107.3 −130.5 120.4 146.0 −92.6 −0.9 176.9

Torsion angles C27-O37-C44-O61 C27-O37-C44-C45 C44-O37-C27-C25 C1-O23-C24-C26 C1-O23-C24-C25 C26-N42-C68-O82 C26-N42-C68-C69

can observe that the calculated bond lengths and bond angles agree with experimental X-ray data, and the B3LYP functional produces an optimized model closer to the experimental crystalline structure, with some exceptions at the values of the torsion angles. The observed differences can be caused by the fact that the theoretical calculations were performed for the gas phase, while the experimental data were

81

obtained for solid phase more precisely, for the X-Ray diffraction analysis [4] the authors crystallized the amikacin from an aqueous solution. The assignment of the vibrational modes of the amikacin found in Table 2 is the result of the interpretation of the IR and Raman spectra illustrated in Figs. 2 and 3. The association of theoretical and experimental bands has been done by comparing the intensity and position of the bands in all spectra. The disagreement existent between the calculated and the experimental wavenumber values could be a consequence of the anharmonicity and of the general tendency of the quantum chemical methods to overestimate the force constants at the exact equilibrium geometry. Nevertheless, as can be observed from Table 2, the theoretical calculations reproduce the experimental data well and allow the assignment of the vibrational modes. Analyzing Table 2 and Figs. 2 and 3, it can be observed that at low wavenumber values the vibrational bands which occur in the spectra of amikacin are given by the deformation vibration of H-C-H from the rings and by the H-N-H rocking vibrations. The most representative band for this spectral range is due to the deformation vibration of the N\\H bond, observable in the Raman spectra at 545 cm−1 as a strong band, respectively as a medium band at 617 cm−1 in the IR spectra (calc. 535, 553 cm−1). The deformations of the two glucosamine rings and of the deoxystreptamine ring have contributions to most of the bands, up to 800 cm−1 in both spectra. Now looking at the IR spectra, all the attentions goes to the intense bands located at 1032, 1048 and 1068 cm−1, with their correspondent bands from Raman spectra at 979, 1045 and 1073 cm−1. These bands are the result of the deformation vibration of the H\\N\\H and stretching vibration of the C\\O bonds. The stretching of the C\\N bond is found in the Raman spectrum as a medium band at 1117 cm−1 and at 1121 cm−1 in the IR spectrum (calc. 1054, 1080 cm−1). Having a view the amikacin structure and looking at the spectra, most precisely at the IR spectrum, the distinguishable peaks from 1551 and 1626 cm−1 with their analogues bands in Raman spectrum confirm that these are the result of the bending vibration of the N\\H bond, respectively the stretching vibration of the C_O bond. At higher wavenumber values (between 2900 and 3600 cm−1) the observed bands are due to the symmetrical and antisymmetrical stretching vibrations of the C\\H or N\\H bonds, and of course to the stretching vibration of the O\\H bond. 3.2. Adsorption of amikacin on the silver nanoparticles surface Afterwards a complete vibrational description of the amikacin molecule was accomplished it was investigated the adsorption behavior of amikacin on the surface of silver nanoparticles by analyzing the recorded SERS spectrum. The SERS effect is characterized by two major processes that occur between the metallic component and investigated molecule, with a significant effect on the Raman intensities. To be more precise, the enhancement of the Raman signal is produced by an electromagnetic mechanism and a chemical one in certain conditions: first, by choosing the right excitation light to resonate with the surface plasmons of the metal nanoparticles, and second, by increasing the molecular polarizability of the analyte when the molecule adsorbed on the metallic substrate [30]. Before performing SERS measurements, to be sure about the right frequency of incident radiation which must resonate with that of the surface plasmons of the metallic nanoparticles, the absorption spectra of silver colloid before and after addition of NaCl and amikacin solution were recorded and are presented in Fig. 4 [31]. As one can see, the pure silver colloid presents a broad peak of absorption with a maximum at 430 nm due to the metallic particle plasmonic resonance. The addition of amikacin to the colloid activated by NaCl solution (Fig. 4b) determines a red-shift and a decrease of this absorption band and the appearance of a new broad absorption signal at longer wavelength values (around 700 nm). This later absorption peak is known to arise from the aggregation of the colloid particles formed upon addition of the adsorbed molecule [32]. Thus, for recording the SERS spectrum the

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Table 2 Selected experimental and theoretical vibrational wavenumbers (cm−1) of the amikacin molecule with their tentative assignment. IR

544 m 582 m 617 m 582 m 704 m 761 m 781 w 813 w 864 w 914 sh m 942 sh m 985 sh m 1032 str 1048 str 1068 str 1092 sh m 1121 m 1145 m 1173 sh w 1181 sh w 1261 w 1302 m 1334 sh 1345 sh 1361 sh 1388 m 1454 m 1551 m 1591 sh m 1626 str 2878 str 2908 str 2923 sh m 2948 str 2972 m 2984 sh m 3004 m 3283 m 3306 m 3328 m 3347 m 3383 m 3481 w

Raman experimental

Theoretical

Solid state

Aqueous solution

BPW9

B3LYP

128 m 157 m 200 w 224 w 250 w 303 w 332 w 410 m 425 sh w 440 m 467 m 519 sh m 545 str 577 m 645 w 708 w 764 m 780 sh m 814 sh w 818 sh w 866 sh m 874 m 894 m 919 m 979 sh m 1045 m 1073 m 1099 sh m 1117 m 1141 sh m 1153 sh m 1183 m 1258 w 1277 m 1299 w 1343 sh m 1358 str 1391 m 1434 m 1463 m 1485 m 1552 w 1601 sh w 1626 m 2843 sh w 2874 m 2908 sh m 2920 sh m 2941 sh m

126 m 152 m 205 w 224 w 246 w 304 w 331 w 409 m 419 m 447 sh m 466 m 521 sh m 543 str 575 m 642 w 709 w 764 m 781 sh m 815 w 819 sh w 865 sh m 873 m 892 m 918 m 980 sh w 1042 m 1080 m 1104 sh m 1113 m 1137 sh m 1150 sh m 1182 m 1256 w 1276 m 1295 m 1343 sh m 1358 str 1389 m 1434 m 1462 m 1485 w 1554 w 1603 w 1629 w

157 201 238 276 306 314 337 365 400 427 472 481 535 553 598 667 699 718 742 752 814 841 854 877 913 951 995 1026 1054 1098 1111 1147 1166 1199 1241 1273 1291 1310 1353 1384 1408 1507 1660 1696 2884 2909 2949 2981 3013 3028 3040 3298 3397 3451 3487 3505 3577

149 225 247 285 313 334 345 364 413 427 481 490 553 571 616 671 698 725 751 778 841 862 877 895 936 1021 1040 1057 1080 1118 1135 1183 1201 1234 1278 1318 1332 1372 1384 1435 1462 1557 1700 1744 2952 2980 3016 3046 3077 3098 3118 3508 3480 3532 3562 3602 3649

3283 str 3343 sh str 3379 sh str 3420 sh m

1

SERS

353 m 407 w 429 w 461 w 517 m 536 m 575 m 663 m 736 m 775 m 808 sh w 836 w 876 w 909 w 960 m 1065 m 1119 sh m

1172 str 1267 str 1294 sh m 1321 sh m 1350 m 1408 sh m 1426 sh w 1454 m 1515 sh w 1544 m 1575 sh m 1623 sh w

Vibrational assignment

H31C28H34, H18C17H19 rock, C1O23C24 bend O80H81, O13H14 bend, H11N10H12, H79N77H78 rock H11N10H12, H31C28H34 rock, OH bend H11N10H12, H41N39H40 rock H11N10H12 rock, O13H14 bend H67N65H67 rock, O55H56, O57H58 bend H67N65H67, H63C62H64 rock, O55H56, O57H58 bend O35H36 bend, ring 1 def, H40N39H41 rock, O15H16 bend H40N39H41 rock, ring 3 def O15H16 bend H40N39H41 twist, ring 2 def ring 1 & 2 def N42H43 bend, ring 2 & 3 def N42H43 bend, CH def of ring 1, H72C71H73 wag N42H43 bend, C27O37C44 wag, CH def of ring 2 H66N65H67, H63N62H64 twist, CC def of ring 3 CH bend of ring 3, O59H60 bend O59H60 bend, CH bend of ring 3 skeletal def H76C74H75, H72C71H73 rock H66N65H67 wag, CH bend of ring 3 H79N77H78 wag H79N77H78 wag H78N77H79 wag H12N10H11 wag H64C62H63 rock, CH def of ring 3 C27O37 stretch, CC def of ring 3 C17O20 stretch C74N77 stretch C4N10 stretch, CH def ring 1 H78N77H79, H76C74H75, H72C71H73 wag, CH bend H78N77H79, H76C74H75, H72C71H73 twist, O80H81, C69H70 bend O80H81, C69H70, N42H43 bend, C68N42 stretch, H72C71H73 twist H66N65H67 twist, CH def of ring 1 H11N10H12 twist, OH bend, CH def of ring 1 skeletal def, H64C62H63, H31C28H34, H18C17H19 twist H78N77H79, H75C74H76, H73C71H72 twist, C69H70 bend CH def of ring 1 & 2, O20H21 bend, H11N10H12 twist H63C62H64 wag, H66N65H67, H11N10H12 twist, CH def of ring 1&2 H63C62H64 wag, CH bend of ring 3, H66N65H67 twist CH bend of ring 2&3, O57H58 bend, H63C62H64 wag N42H43 bend H78N77H79 sciss C68O82 stretch, N42H43 bend CH stretch HCH sym & asym stretch

OH stretch NHN sym & asym stretch NH stretch

OH stretch

2

Calculated with: BPW91/6–31+G* and B3LYP/6–31+G*. Abbreviations: w-weak, m-medium, sh-shoulder, str-strong, rock-rocking, sciss-scissoring, bend-bending, def-deformation, stretch-stretching, twist-twisting, wag-wagging, symsymmetrical, asym-asymmetrical, ring 1-glucosamine ring with oxygen atom labeled as O22, ring 2-deoxystreptamine ring, ring 3-glucosamine ring with oxygen atom labeled as O61.

532 nm laser line, which is able to induce the resonance of the surface plasmons, was chosen. Fig. 5 shows the SERS spectrum of amikacin in comparison with the Raman spectra of solid state and concentrated amikacin solution. A close analysis of Fig. 5 reveals no changes in the Raman spectrum of the amikacin solution in comparison with the solid-state spectrum besides the small change of the bands position as one can see from Table 2. To understand and predict the way in which amikacin interacts with the plasmonic structures the molecular electrostatic potential (MEP) was calculated, for the optimized geometry of the theoretical model. The

results of the B3LYP/6-31+G* calculation can be seen in the Fig. 6, as an 3D RGB map of the optimized amikacin obtained for an electron density isovalue of 0.020 (a.u). Based on the results illustrated in Fig. 6 the regions with high electron density, marked with red/yellow colors, represent the possible places where the adsorption can happen. So, those located around skeletal oxygens both from O\\H and C_O bonds, and around the N atom from the glucosamine ring, denoted ring 1, respectively denote different adsorption behavior of the amikacin on the metal structure. Thus, it is possible that the amplification of the Raman signal is due to the interactions of these groups of atoms and

1696

1507

Absorbance

1551

1121 995 913 951 1054

IR-bpw91

532 nm

b a

553

IR-b3lyp

1744

9361021 1080

1557

1040

535

Absorbtion (a.u.)

617

FT-IR

83

1626

1032 1048 1068

C. Balan et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 214 (2019) 79–85

300

400

500

600

700

800

900

Wavelength / nm 500

1000

1500

2800

3200

Wavenumber /cm

3600

-1

Fig. 4. UV-VIS absorption spectra of silver colloid before (a) and after addition of NaCl and amikacin solution (b).

Fig. 2. Experimental and simulated IR spectra of amikacin obtained at B3LYP/6-31+G* (blue line) and BPW91/6-31+G* (red line) theoretical levels.

1623

1454

1544

1344 1408

1267 1172 663

1391

1626

1183

1256

1626

1268

1183

979 979

1391

960

575

645

577 577

Raman - solid state 645

Raman Intensity (a.u.)

1696

SERS

1744

913 951 995 1054

1507 1507

553

1080

Raman-b3lyp

936 1021 1040

Raman-bpw91 535

Raman intensity (a.u.)

545

979 1045 1073 1117

Raman

1552 1626

silver nanoparticles, which will further induce some shifts of the bands beside the Raman signal enhancement. By analyzing the spectra from Fig. 5., one can observe the shifts of some SERS bands compared to the corresponding Raman bands of the amikacin solution, which confirm the chemisorption of the molecule through some of its constituent groups, while other groups are located at a relatively large distance from the metal surface and therefore their vibrations are not influenced by adsorption. Moreover, by using the surface selection rules for Raman scattering [33–36] the orientation of the adsorbed amikacin molecule can be deduced. According to these rules, if the molecular axis (z-axis) is normal

to the surface, then vibrations of the adsorbed molecule, which have a polarizability tensor component along this axis, will be preferentially enhanced. The amikacin molecule has a very low symmetry and all vibrations have polarizability tensor component along the z-axis. However, stretching vibrations are supposed to have the larger component along the bond axis and consequently, stretches that are orthogonal to the metal surface will exhibit different intensities in SERS and normal Raman spectra [34]. By analyzing the SERS and Raman spectra of amikacin from Fig. 5 and taking into account the assignment of the vibrational modes summarized in Table 2, one can observe that the most enhanced bands from the SERS spectrum are due to vibrations of skeletal bonds. Thus, the bands at 575 and 663 cm−1 are mainly due to the N42\\H bending vibration. Moreover, the other most intense peaks from the SERS spectrum from 1172 and 1267 cm−1, are assigned to the bending vibration of the skeletal O80\\H bond and also to the deformation vibration of the N42\\H bond. At higher wavenumber values the bands at 1350 and 1544 cm−1 given by the deformation vibration of the skeletal N77\\H and N42\\H bond, respectively are also enhanced in the SERS spectrum as compared to the corresponding ones from the Raman

Raman - solution

400

800

1200

1600

2700 3000 3300 3600

Wavenumber / cm

-1

Fig. 3. Experimental and simulated Raman spectra of amikacin obtained at B3LYP/6-31 +G* (blue line) and BPW91/6-31+G* (red line) theoretical levels.

200

400

600

800

1000

1200

Wavenumber / cm

1400

1600

1800

-1

Fig. 5. Experimental Raman (solid state and 1 M aqueous solution) and SERS spectra of amikacin.

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Fig. 6. The 3D map of electrostatic potential of amikacin, calculated with B3LYP/6–3 ± 1G* for an electronic isovalue of 0.02 (a.u.).

spectrum. Furthermore, having in view the high density around the C_O in MEP of amikacin, it not surprising that the band at 1623 cm−1 due to the stretching vibration of this group is also enhanced in the SERS spectrum. The other peaks from SERS spectrum do not presents an impressive amplification, which means that the amikacin chemisorption is accomplished by those groups of the skeletal part of the molecule, whose vibrations have been amplified in the SERS spectrum, most probably through the oxygen atom of the carbonyl group. Moreover, one can assume that the rings are located at relatively large distance from the nanoparticle surface and therefore their vibrational modes are not as enhanced as those of the skeletal bonds. On the other hand, having in view the complex structure of the amikacin molecule it is not possible to establish the exact orientation of the adsorbed molecule to the metal surface. By analyzing the enhancement of the SERS bands in agreement with the predictions of surface selection rules the tilted orientation of the adsorbed species with respect to the silver nanoparticles surface can be assumed. 4. Conclusions This study presents a comparative analysis of amikacin that was investigated by FT-IR and Raman spectroscopy in conjunction with theoretical calculations. The DFT calculations were carried out with BPW91 and B3LYP functionals coupled with 6-31+G* as basis set and with their help the assignment of the vibrational modes was accomplished. The obtained theoretical data not only for the wavenumber values, but also for the structural parameters of the molecule are found to be close to the experimental values. The SERS spectrum of amikacin was also recorded and analyzed and the chemisorption of the molecule most probably through the oxygen atom of the skeletal carbonyl group was assumed. The amikacin adsorption occurs so that the

glucosamine and deoxystreptamine rings are situated at a relative large distance from the metallic surface.

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