Specific Interaction of Tricyclic Antidepressants with Gold and Silver Nanostructures as Revealed by Combined One- and Two-Photon Vibrational Spectroscopy

Abstract

We report two-photon excited nonresonant surface-enhanced hyper Raman scattering (SEHRS) spectra of tricyclic antidepressant (TCA) molecules during their interaction with biocompatible gold nanostructures and with silver nanostructures. The SEHRS spectra of amitriptyline, desipramine, and imipramine are compared with surface-enhanced Raman scattering (SERS) spectra on both kinds of nanoparticles, obtained with excitation at 532 and 785 nm. The SEHRS spectra of the TCA molecules show several intense contributions by infrared-active vibrations. Combining SEHRS with SERS therefore enables a comprehensive vibrational characterization of the interaction of the molecules with the nanostructures. SEHRS and SERS data indicate that the molecules interact with the silver nanostructures mainly via their ring moiety. In contrast, in the interaction with gold, the methylaminopropyl side chain plays a very important role, along with parts of the ring system. It is possible to obtain the spectra of the molecules with near-infrared excitation and with gold nanoparticles in cell culture media. The spectral signatures of the drug molecules collected at low pH values characteristic of late endosomal stages or of acidified tissues are very stable and show only small changes in the interaction of the TCA with the gold nanoparticles. The results will help to develop tools for the characterization of new nanoparticle-based drug delivery platforms in real biological environments.

Bio‐probing with nonresonant surface‐enhanced hyper‐Raman scattering excited at 1,550 nm

“…[15] Both spectra display bands at $1,295 and $1,160 cm −1 , which could be assigned to the bridge bond C-C stretching of the sevenmembered ring and the C-H in-plane bending vibration of the aromatic rings, respectively (Table 1). [42,43] These bands were observed with similar intensities relative to each other as they were also found in the 1,064 nm-excited SEHRS spectra of the drugs. [43] Some bands that were found in the spectra excited at 1,064 nm reported previously [43] were not observed in the spectra measured here (Figure 3), because of the lower sensitivity of the experiment here.…”

“…[42,43] These bands were observed with similar intensities relative to each other as they were also found in the 1,064 nm-excited SEHRS spectra of the drugs. [43] Some bands that were found in the spectra excited at 1,064 nm reported previously [43] were not observed in the spectra measured here (Figure 3), because of the lower sensitivity of the experiment here. This is, on the one hand, due to a different plasmonic enhancement [34] generated by nanoaggregates formed by the drug molecules [43] at this wavelength and, on the other hand, due to the overall lower signals caused by very low excitation intensity, preventing weaker bands from appearing in the spectrum.…”

“…[43] Some bands that were found in the spectra excited at 1,064 nm reported previously [43] were not observed in the spectra measured here (Figure 3), because of the lower sensitivity of the experiment here. This is, on the one hand, due to a different plasmonic enhancement [34] generated by nanoaggregates formed by the drug molecules [43] at this wavelength and, on the other hand, due to the overall lower signals caused by very low excitation intensity, preventing weaker bands from appearing in the spectrum. Because the observation of the tricyclic antidepressant molecules in live cells by SERS is very challenging and is mainly solved by screening of data sets with machine learning tools, [15] fast near-infrared (IR) vibrational imaging by SEHRS could generate additional fingerprint-like data to identify spectral features of the drug molecules in cells in combined SERS and SEHRS vibrational imaging.…”

“…In contrast, the intensity difference in the SEHRS spectra of CV using silver and 50-nm gold nanoparticles is only about a factor of 2. Based on the concentration and size of the nanoparticles and of the molecules, the available surface areas for the different types of nanoparticles were approximately the same, suggesting that the observed [39,[41][42][43][44][45][46] Raman shift, cm −1 Assignment CV [44,45] 1,618 differences in signal strength originate from a different interaction of the thiolated molecules with the gold and the silver surfaces, respectively. This may, particularly, concern thermodynamic and kinetic aspects of formation of the thiol-based self-assembled monolayers on silver and gold surfaces.…”

Surface-Enhanced Hyper Raman Spectra of Aromatic Thiols on Gold and Silver Nanoparticles

“… 17 − 21 In particular, HRS follows different selection rules than those acting in RS, and therefore, SEHRS can provide complementary vibrational information, specifically from IR active and silent modes. 18 , 22 , 23 Moreover, SEHRS is more sensitive than SERS with respect to adsorbate orientation and surface environmental changes. 17 , 24 − 27 The high local field enhancements observed recently in resonant SEHRS experiments with gold nanostructures 28 , 29 are very promising for exploiting SEHRS as an approach to probe molecules on gold surfaces excited off-resonance as well.…”