Nano Research

, Volume 11, Issue 8, pp 4401–4411 | Cite as

Polarization effect in tip-enhanced infrared nanospectroscopy studies of the selective Y5 receptor antagonist Lu AA33810

  • Natalia Piergies
  • Ewa Pięta
  • Czesława Paluszkiewicz
  • Helena Domin
  • Wojciech M. Kwiatek
Open Access
Research Article


A novel approach of combining conventional infrared spectroscopy (IR) and atomic force microscopy (AFM) is presented to better understand the behavior of a drug adsorbed on a metal substrate at the nanoscale level. Tip-enhanced infrared nanospectroscopy (TEIRA) was used for the first time to investigate Lu AA33810, a selective brain-penetrating Y5 receptor antagonist, after immobilization on gold nanoparticles (GNPs). Here, a gold coated AFM tip and gold substrate were used to obtain the near-field electromagnetic field trapping effect. Because of the huge signal enhancement, it was possible to obtain the spectral information regarding the self-assembled monolayer of the investigated molecule. The effect of two orthogonal polarizations (p- and s-polarization modulations) of the excitation laser beam on the spectral patterns is also discussed. The results show that there is a strong relationship between the state of polarization of the incident radiation and the relative infrared band intensities. Another factor affecting the observed spectral differences is the topology of the metal substrate, which may result in the induction of a cross-polarization effect. The performed analysis indicates that the C–C bond from the cyclohexyl group is oriented almost parallel to the metal surface. Conversely, the p- and s-polarized spectral variations suggest that the O=S=O angle is high enough to enable the simultaneous interaction of both oxygen atoms with the GNPs.


tip-enhanced infrared nanospectroscopy polarization modulation Y5 receptor antagonist gold nanoparticles adsorption 



The research was performed by the use of the equipment purchased in the frame of the project co-funded by the Małopolska Regional Operational Program Measure 5.1 Krakow Metropolitan Area as an important hub of the European Research Area for 2007–2013 (No. MRPO.05.01.00–12–013/15). This work was also supported by the National Science Centre Poland (No. 2016/21/D/ ST4/02178 to N. P. and 2017/01/X/ST4/00428 to E. P.). The authors gratefully acknowledge M. Oćwieja, Ph. D, J. Haber Institute of Catalysis and Surface Chemistry, Polish Academy of Sciences, for GNPs synthesis.


  1. [1]
    Goswami, A.; Dhandaria, P.; Pal, S.; McGee, R.; Khan, F.; Antić, Z.; Gaikwad, R.; Prashanthi, K.; Thundat, T. Effect of interface on mid-infrared photothermal response of MoS2 thin film grown by pulsed laser deposition. Nano Res. 2017, 10, 3571–3584.CrossRefGoogle Scholar
  2. [2]
    Vitry, P.; Rebois, R.; Bourillot, E.; Deniset-Besseau, A.; Virolle, M. J.; Lesniewska, E.; Dazzi A. Combining infrared and mode synthesizing atomic force microscopy: Application to the study of lipid vesicles inside Streptomyces bacteria. Nano Res. 2016, 9, 1674–1681.CrossRefGoogle Scholar
  3. [3]
    Aroca, R. F.; Ross, D. J.; Domingo, C. Surface-enhanced infrared spectroscopy. Appl. Spectrosc. 2004, 58, 324A–338A.CrossRefGoogle Scholar
  4. [4]
    Hartstein, A.; Kirtley, J. R.; Tsang, J. C. Enhancement of the infrared absorption from molecular monolayers with thin metal overlayers. Phys. Rev. Lett. 1980, 45, 201–204.CrossRefGoogle Scholar
  5. [5]
    Qian, H. M.; Xu, M.; Li, X. W.; Ji, M. W.; Cheng, L.; Shoaib, A.; Liu, J. J.; Jiang L.; Zhu, H. S.; Zhang, J. T. Surface micro/nanostructure evolution of Au–Ag alloy nanoplates: Synthesis, simulation, plasmonic photothermal and surface-enhanced Raman scattering applications. Nano Res. 2016, 9, 876–885.CrossRefGoogle Scholar
  6. [6]
    Khlebtsov, B.; Khanadeev, V.; Khlebtson, N. Surface-enhanced Raman scattering inside Au@Ag core/shell nanorods. Nano Res. 2016, 9, 2303–2318.CrossRefGoogle Scholar
  7. [7]
    Wang, Y. D.; Lu, N.; Wang, W. T.; Liu, L. X.; Feng, L. F.; Zeng, Z. F.; Li, H. B.; Xu, W. Q.; Wu, Z. J.; Hu, W. et al. Highly effective and reproducible surface-enhanced Raman scattering substrates based on Ag pyramidal arrays. Nano Res. 2013, 6, 159–166.CrossRefGoogle Scholar
  8. [8]
    Osawa, M. Surface-enhanced infrared absorption. In Near-Field Optics and Surface Plasmon Polaritons. Kawata, S., Ed.; Springer-Verlag: Berlin, Heidelberg, 2001; pp 163–187.CrossRefGoogle Scholar
  9. [9]
    Joshi, P.; Chakraborti, S.; Ramirez-Vick, J. E.; Ansari, Z. A.; Shanker, V.; Chakrabarti, P.; Singh, S. P. The anticancer activity of chloroquine-gold nanoparticles against MCF-7 breast cancer cells. Colloid. Surface B 2012, 95, 195–200.CrossRefGoogle Scholar
  10. [10]
    Brigger, I.; Dubernet, C.; Couvreur, P. Nanoparticles in cancer therapy and diagnosis. Adv. Drug Deliver Rev. 2012, 64, 24–36.CrossRefGoogle Scholar
  11. [11]
    El-Ansary, A.; Faddah L. M. Nanoparticles as biochemical sensors. Nanotechnol. Sci. Appl. 2010, 3, 65–76.CrossRefGoogle Scholar
  12. [12]
    Wang, E. C.; Wang A. Z. Nanoparticles and their applications in cell and molecular biology. Integr. Biol. 2014, 6, 9–26.CrossRefGoogle Scholar
  13. [13]
    Kreuter, J. Drug delivery to the central nervous system by polymeric nanoparticles: What do we know? Adv. Drug Deliver Rev. 2014, 71, 2–14.CrossRefGoogle Scholar
  14. [14]
    Lipiec, E.; Sekine, R.; Bielecki, J.; Kwiatek, W. M.; Wood, B. R. Molecular characterization of DNA double strand breaks with tip-enhanced Raman scattering. Angew. Chem. 2014, 126, 173–176.CrossRefGoogle Scholar
  15. [15]
    Święch, D.; Ozaki, Y.; Kim, Y.; Proniewicz, E. Surface- and tip-enhanced Raman scattering of bradykinin onto the colloidal suspended Ag surface. Phys. Chem. Chem. Phys. 2015, 17, 17140–17149.CrossRefGoogle Scholar
  16. [16]
    Lu, F.; Jin, M. Z.; Belkin, M. A. Tip-enhanced infrared nanospectroscopy via molecular expansion force detection. Nat. Photonics 2014, 8, 307–312.CrossRefGoogle Scholar
  17. [17]
    Ruggeri, F. S.; Vieweg, S.; Cendrowska, U.; Longo, G.; Chiki, A.; Lashuel, H. A.; Dietler G. Nanoscale studies link amyloid maturity with polyglutamine diseases onset. Sci. Rep. 2016, 6, 31155.CrossRefGoogle Scholar
  18. [18]
    Dazzi, A.; Prazeres, R.; Glotin, F.; Ortega, J. M. Local infrared microspectroscopy with subwavelength spatial resolution with an atomic force microscope tip used as a photothermal sensor. Opt. Lett. 2005, 30, 2388–2390.CrossRefGoogle Scholar
  19. [19]
    Dazzi, A.; Prazeres, R.; Glotin, F.; Ortega, J. M. Subwavelength infrared spectromicroscopy using an AFM as a local absorption sensor. Infrared Phys. Technol. 2006, 49, 113–121.CrossRefGoogle Scholar
  20. [20]
    Dazzi, A.; Prater, C. B. AFM-IR: Technology and applications in nanoscale infrared spectroscopy and chemical imaging. Chem. Rev. 2017, 117, 5146–5173.CrossRefGoogle Scholar
  21. [21]
    Petibois, C.; Piccinini, M.; Guidi, M. C.; Marcelli, A. Facing the challenge of biosample imaging by FTIR with a synchrotron radiation source. J. Synchrotron Rad. 2010, 17, 1–11.CrossRefGoogle Scholar
  22. [22]
    Nasse, M. J.; Walsh, M. J.; Mattson, E. C.; Reininger, R.; Kajdacsy-Balla, A.; Macias, V.; Bhargava, R.; Hirschmugl, C. J. High-resolution Fourier-transform infrared chemical imaging with multiple synchrotron beams. Nat. Methods 2011, 8, 413–416.CrossRefGoogle Scholar
  23. [23]
    Reddy, R. K.; Walsh, M. J.; Schulmerich, M. V.; Carney, P. S.; Bhargava, R. High-definition infrared spectroscopic imaging. Appl. Spectrosc. 2013, 67, 93–105.CrossRefGoogle Scholar
  24. [24]
    Findlay, C. R.; Wiens, R.; Rak, M.; Sedlmair, J.; Hirschmugl, C. J.; Morrison, J.; Mundy, C. J.; Kansiz, M.; Gough, K. M. Rapid biodiagnostic ex vivo imaging at 1 μm pixel resolution with thermal source FTIR FPA. Analyst 2015, 140, 2493–2503.CrossRefGoogle Scholar
  25. [25]
    Dazzi, A.; Prater, C. B.; Hu, Q. C.; Chase, D. B.; Rabolt, J. F.; Marcott, C. AFM-IR: Combining atomic force microscopy and infrared spectroscopy for nanoscale chemical characterization. Appl. Spectrosc. 2012, 66, 1365–1384.CrossRefGoogle Scholar
  26. [26]
    Centrone, A.; Lahiri, B.; Holland, G. E. Chemical imaging beyond the diffraction limit using photothermal induced resonance microscopy. Microsc. Anal. 2013, 27, 6–9.Google Scholar
  27. [27]
    Ruggeri, F. S.; Habchi, J.; Cerreta, A.; Dietler, G. AFM-based single molecule techniques: Unraveling the amyloid Pathogenic Species. Curr. Pharm. Design 2016, 22, 3950–3970.CrossRefGoogle Scholar
  28. [28]
    Paluszkiewicz, C.; Piergies, N.; Chaniecki, P.; Rękas, M.; Miszczyk, J.; Kwiatek, W. M. Differentiation of protein secondary structure in clear and opaque human lenses: AFM–IR studies. J. Pharmaceut. Biomed. 2017, 139, 125–132.CrossRefGoogle Scholar
  29. [29]
    Jackson, M.; Mantsch, H. H. The use and misuse of FTIR spectroscopy in the determination of protein structure. Crit. Rev. Biochem. Mol. 1995, 30, 95–120.CrossRefGoogle Scholar
  30. [30]
    Greenler, R. G. Infrared study of adsorbed molecules on metal surfaces by reflection techniques. J. Chem. Phys. 1966, 44, 310–315.CrossRefGoogle Scholar
  31. [31]
    Ras, H. A. R.; Schoonheydt, R. A.; Johnston, C. T. Relation between s-polarized and p-polarized internal reflection spectra: Application for the spectral resolution of perpendicular vibrational modes. J. Phys. Chem. A 2007, 111, 8787–8791.CrossRefGoogle Scholar
  32. [32]
    Frey, B. L.; Corn, R. M.; Weibel, S. C. Polarization-modulation approaches to reflection-absorption spectroscopy. In Handbook of Vibrational Spectroscopy. Griffiths, P. R., Ed.; John Wiley & Sons: New York, 2001; pp 1042–1056.Google Scholar
  33. [33]
    Paluszkiewicz, C.; Handke, M.; Aleksandrowicz, R. Application of FT-IR spectroscopy to phosphate coatings on electrotechnical iron sheets. J. Mol. Structure 1984, 114, 433–436.CrossRefGoogle Scholar
  34. [34]
    Handke, M.; Paluszkiewicz, C. FTIR spectra of thin inorganic coatings on metals. Infrared Phys. 1984, 24, 121–128.CrossRefGoogle Scholar
  35. [35]
    Handke, M.; Milosevic, M.; Harrick, N. J. External reflection Fourier transform infrared spectroscopy: Theory and experimental problems. Vibrat. Spectrosc. 1991, 1, 251–262.CrossRefGoogle Scholar
  36. [36]
    Guo, P.-F.; Huang, W.-Y.; Liu, H.-B.; Xiao, S.-J. AFM and multiple transmission-reflection infrared spectroscopy (MTR-IR) studies on formation of air-stable supported lipid bilayers. Int. J. Mol. Sci. 2009, 10, 1407–1418.CrossRefGoogle Scholar
  37. [37]
    Ataka, K.; Stripp, S. T.; Heberle, J. Surface-enhanced infrared absorption spectroscopy (SEIRAS) to probe monolayers of membrane proteins. Biochim. Biophys. Acta 2013, 1828, 2283–2293.CrossRefGoogle Scholar
  38. [38]
    Osawa, M.; Ataka, K.; Yoshii, K.; Yotsuyanagi, T. Surface-enhanced infrared ATR spectroscopy for in situ studies of electrode/electrolyte interfaces. J. Electron Spectrosc. Related Phenomena 1993, 64–65, 371–379.CrossRefGoogle Scholar
  39. [39]
    Aroca, R. SERS/SERRS, the analytical tool. In Surface-Enhanced Vibrational Spectroscopy. Aroca, R., Ed.; John Wiley & Sons Ltd: Chichester, UK, 2006; pp 164–176.CrossRefGoogle Scholar
  40. [40]
    Walker, M. W.; Wolinsky, T. D.; Jubian, V.; Chandrasena, G.; Zhong, H. L.; Huang, X. Y.; Miller, S.; Hegde, L. G.; Marsteller, D. A.; Marzabadi, M. R. et al. The novel neuropeptide Y Y5 receptor antagonist Lu AA33810 [N-[[trans-4-[(4,5-Dihydro[1]benzothiepino[5,4-d]thiazol-2-yl)amino]cyclohexyl] methyl]-methanesulfonamide] exerts anxiolytic- and antidepressant-like effects in rat models of stress sensitivity. J. Pharmacol. Exp. Ther. 2009, 328, 900–911.CrossRefGoogle Scholar
  41. [41]
    Packiarajan, M.; Marzabadi, M. R.; Desai, M.; Lu, Y. L.; Noble, S. A.; Wong, W. C.; Jubian, V.; Chandrasena, G.; Wolinsky, T. D.; Zhong, H. L. et al. Discovery of Lu AA33810: A highly selective and potent NPY5 antagonist with in vivo efficacy in a model of mood disorder. Bioorg. Med. Chem. Lett. 2011, 21, 5436–5441.CrossRefGoogle Scholar
  42. [42]
    Heilig, M. The NPY system in stress, anxiety and depression. Neuropeptides 2004, 38, 213–224.CrossRefGoogle Scholar
  43. [43]
    Morales-Medina, J. C.; Dumont, Y.; Quirion, R. A possible role of neuropeptide Y in depression and stress. Brain Res. 2010, 1314, 194–205.CrossRefGoogle Scholar
  44. [44]
    Domin, H.; Szewczyk, B.; Pochwat, B.; Woźniak, M.; Śmiałowska, M. Antidepressant-like activity of the neuropeptide Y Y5 receptor antagonist Lu AA33810: Behavioral, molecular, and immunohistochemical evidence. Psychopharmacology. 2017, 234, 631–645.CrossRefGoogle Scholar
  45. [45]
    Pięta, E.; Piergies, N.; Oćwieja, M.; Domin, H.; Paluszkiewicz, C.; Bielańska, E.; Kwiatek, W. M. Monitoring the interfacial behavior of selective Y5 receptor antagonist on colloidal gold nanoparticle surfaces: Surface-enhanced vibrational spectroscopy studies. J. Phys. Chem. C 2017, 121, 17276–17288.CrossRefGoogle Scholar
  46. [46]
    Domin, H.; Pięta, E.; Piergies, N.; Święch, D.; Kim, Y. Proniewicz, L. M.; Proniewicz, E. Neuropeptide Y and its C-terminal fragments acting on Y2 receptor: Raman and SERS spectroscopy studies. J. Colloid Interf. Sci. 2015, 437, 111–118.CrossRefGoogle Scholar
  47. [47]
    Lahiri, B.; Holland, G.; Aksyuk, V.; Centrone, A. Nanoscale imaging of plasmonic hot spots and dark modes with the photothermal-induced resonance technique. Nano Lett. 2013, 13, 3218–3224.CrossRefGoogle Scholar
  48. [48]
    Chae, J.; Lahiri, B.; Centrone A. Engineering near-field seira enhancements in plasmonic resonators. ACS Photonics 2016, 3, 87–95.CrossRefGoogle Scholar
  49. [49]
    Pięta, E.; Paluszkiewicz, C.; Oćwieja, M.; Kwiatek, W. M. Potential drug-nanosensor conjugates: Raman, infrared absorption, surface-enhanced Raman, and density functional theory investigations of indolic molecules. Appl. Surf. Sci. 2017, 404, 168–179.CrossRefGoogle Scholar
  50. [50]
    Purcell, S. M.; Barker, P. F. Tailoring the optical dipole force for molecules by field-induced alignment. Phys. Rev. Lett. 2009, 103, 153001.CrossRefGoogle Scholar
  51. [51]
    Yu, Y. Q.; Lin, K.; Zhou, X. G.; Wang, H.; Liu, S. L.; Ma, X. X. New C−H stretching vibrational spectral features in the Raman spectra of gaseous and liquid ethanol. J. Phys. Chem. C 2007, 111, 8971–8978.CrossRefGoogle Scholar
  52. [52]
    Leverette, C. L.; Jacobs, S. A.; Shanmukh, S.; Chaney, S. B.; Dluhy, R. A.; Zhao, Y.-P. Aligned silver nanorod arrays as substrates for surface-enhanced infrared absorption spectroscopy. Appl. Spectrosc. 2006, 60, 906–913.CrossRefGoogle Scholar

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Open Access: This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

Authors and Affiliations

  1. 1.Institute of Nuclear PhysicsPolish Academy of SciencesKrakowPoland
  2. 2.Institute of PharmacologyPolish Academy of Sciences, Department of NeurobiologyKrakowPoland

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