ACS Publications. Most Trusted. Most Cited. Most Read
My Activity

Figure 1Loading Img

Interactions of Ibuprofen with Hybrid Lipid Bilayers Probed by Complementary Surface-Enhanced Vibrational Spectroscopies

View Author Information
Department of Chemistry, Department of Bioengineering, Department of Electrical and Computer Engineering, Rice University, P.O. Box 1892, Houston, Texas 77251-1892
* To whom correspondence should be addressed. E-mail: [email protected]
†These authors contributed equally to this work.
§Department of Chemistry.
#Department of Bioengineering.
ξDepartment of Electrical and Computer Engineering.
Cite this: J. Phys. Chem. B 2008, 112, 45, 14168–14175
Publication Date (Web):October 22, 2008
Copyright © 2008 American Chemical Society

    Article Views





    Other access options
    Supporting Info (1)»


    The incorporation of small molecules into lipid bilayers is a process of biological importance and clinical relevance that can change the material properties of cell membranes and cause deleterious side effects for certain drugs. Here we report the direct observation, using surface-enhanced Raman and IR spectroscopies (SERS, SEIRA), of the insertion of ibuprofen molecules into hybrid lipid bilayers. The alkanethiol-phospholipid hybrid bilayers were formed onto gold nanoshells by self-assembly, where the underlying nanoshell substrates provided the necessary enhancements for SERS and SEIRA. The spectroscopic data reveal specific interactions between ibuprofen and phospholipid moieties and indicate that the overall hydrophobicity of ibuprofen plays an important role in its intercalation in these membrane mimics.

    Read this article

    To access this article, please review the available access options below.

    Get instant access

    Purchase Access

    Read this article for 48 hours. Check out below using your ACS ID or as a guest.


    Access through Your Institution

    You may have access to this article through your institution.

    Your institution does not have access to this content. You can change your affiliated institution below.

    Supporting Information

    Jump To

    Detailed experimental procedures and the unenhanced Raman spectrum for a 500 mM aqueous solution of sodium ibuprofenate are provided. This material is available free of charge via the Internet at

    Terms & Conditions

    Most electronic Supporting Information files are available without a subscription to ACS Web Editions. Such files may be downloaded by article for research use (if there is a public use license linked to the relevant article, that license may permit other uses). Permission may be obtained from ACS for other uses through requests via the RightsLink permission system:

    Cited By

    This article is cited by 68 publications.

    1. Guangyang Xu, Wei Li, Han Xie, Jinyu Zhu, Li Song, Jinping Tang, Yu Miao, Xiao Xia Han. In Situ Monitoring of Membrane Protein Electron Transfer via Surface-Enhanced Resonance Raman Spectroscopy. Analytical Chemistry 2024, 96 (1) , 6-11.
    2. Andrés B. Sánchez-Alvarado, Jingyi Zhou, Peixuan Jin, Oara Neumann, Thomas P. Senftle, Peter Nordlander, Naomi J. Halas. Combined Surface-Enhanced Raman and Infrared Absorption Spectroscopies for Streamlined Chemical Detection of Polycyclic Aromatic Hydrocarbon-Derived Compounds. ACS Nano 2023, 17 (24) , 25697-25706.
    3. Rossana Terracciano, Yareli Carcamo-Bahena, Amber Lee R. Royal, Luca Messina, Jack Delk, E. Brian Butler, Danilo Demarchi, Alessandro Grattoni, Zhihui Wang, Vittorio Cristini, Prashant Dogra, Carly S. Filgueira. Zonal Intratumoral Delivery of Nanoparticles Guided by Surface Functionalization. Langmuir 2022, 38 (45) , 13983-13994.
    4. Mathieu L. Simeral, Aobo Zhang, Steven M. E. Demers, Hannah J. Hughes, Mohammad Abdul-Moqueet, Kathryn M. Mayer, Jason H. Hafner. Effects of Conformational Variation on Structural Insights from Solution-Phase Surface-Enhanced Raman Spectroscopy. The Journal of Physical Chemistry B 2021, 125 (8) , 2031-2041.
    5. Arif M. Siddiquee, Aamd Houri, Kibret A. Messalea, Jiao Lin, Torben Daeneke, Brian Abbey, Adam Mechler, Shanshan Kou. Nanoscale Probing of Cholesterol-Rich Domains in Single Bilayer Dimyristoyl-Phosphocholine Membranes Using Near-Field Spectroscopic Imaging. The Journal of Physical Chemistry Letters 2020, 11 (21) , 9476-9484.
    6. Ian Bruzas, Bruce E. Brinson, Zohre Gorunmez, William Lum, Emilie Ringe, Laura Sagle. Surface-Enhanced Raman Spectroscopy of Fluid-Supported Lipid Bilayers. ACS Applied Materials & Interfaces 2019, 11 (36) , 33442-33451.
    7. Miftah Faried, Keishi Suga, Yukihiro Okamoto, Kamyar Shameli, Mikio Miyake, Hiroshi Umakoshi. Membrane Surface-Enhanced Raman Spectroscopy for Cholesterol-Modified Lipid Systems: Effect of Gold Nanoparticle Size. ACS Omega 2019, 4 (9) , 13687-13695.
    8. Jay P. Kitt, David A. Bryce, Shelley D. Minteer, Joel M. Harris. Confocal Raman Microscopy Investigation of Self-Assembly of Hybrid Phospholipid Bilayers within Individual Porous Silica Chromatographic Particles. Analytical Chemistry 2019, 91 (12) , 7790-7797.
    9. James R. Matthews, Cyna R. Shirazinejad, Grace A. Isakson, Steven M. E. Demers, and Jason H. Hafner . Structural Analysis by Enhanced Raman Scattering. Nano Letters 2017, 17 (4) , 2172-2177.
    10. Xueming Su, Yunqing Wang, Wenhai Wang, Kaoxiang Sun, and Lingxin Chen . Phospholipid Encapsulated AuNR@Ag/Au Nanosphere SERS Tags with Environmental Stimulus Responsive Signal Property. ACS Applied Materials & Interfaces 2016, 8 (16) , 10201-10211.
    11. Amanda Quirk, Michael J. Lardner, Zin Tun, and Ian J. Burgess . Surface-Enhanced Infrared Spectroscopy and Neutron Reflectivity Studies of Ubiquinone in Hybrid Bilayer Membranes under Potential Control. Langmuir 2016, 32 (9) , 2225-2235.
    12. James R. Matthews, Courtney M. Payne, and Jason H. Hafner . Analysis of Phospholipid Bilayers on Gold Nanorods by Plasmon Resonance Sensing and Surface-Enhanced Raman Scattering. Langmuir 2015, 31 (36) , 9893-9900.
    13. Keishi Suga, Tomohiro Yoshida, Haruyuki Ishii, Yukihiro Okamoto, Daisuke Nagao, Mikio Konno, and Hiroshi Umakoshi . Membrane Surface-Enhanced Raman Spectroscopy for Sensitive Detection of Molecular Behavior of Lipid Assemblies. Analytical Chemistry 2015, 87 (9) , 4772-4780.
    14. Reid E. Messersmith, Greg J. Nusz, and Scott M. Reed . Using the Localized Surface Plasmon Resonance of Gold Nanoparticles To Monitor Lipid Membrane Assembly and Protein Binding. The Journal of Physical Chemistry C 2013, 117 (50) , 26725-26733.
    15. Cristiano D’Andrea, Jörg Bochterle, Andrea Toma, Christian Huck, Frank Neubrech, Elena Messina, Barbara Fazio, Onofrio M. Maragò, Enzo Di Fabrizio, Marc Lamy de La Chapelle, Pietro G. Gucciardi, and Annemarie Pucci . Optical Nanoantennas for Multiband Surface-Enhanced Infrared and Raman Spectroscopy. ACS Nano 2013, 7 (4) , 3522-3531.
    16. Kyle C. Bantz, Heidi D. Nelson, and Christy L. Haynes . Plasmon-Enabled Study of Self-Assembled Alkanethiol Ordering on Roughened Ag Substrates. The Journal of Physical Chemistry C 2012, 116 (5) , 3585-3593.
    17. Matthew R. Jones, Kyle D. Osberg, Robert J. Macfarlane, Mark R. Langille, and Chad A. Mirkin . Templated Techniques for the Synthesis and Assembly of Plasmonic Nanostructures. Chemical Reviews 2011, 111 (6) , 3736-3827.
    18. Shell Ip, Christina M. MacLaughlin, Nikhil Gunari, and Gilbert C. Walker . Phospholipid Membrane Encapsulation of Nanoparticles for Surface-Enhanced Raman Scattering. Langmuir 2011, 27 (11) , 7024-7033.
    19. Edward T. Castellana, Roberto C. Gamez, and David H. Russell . Label-Free Biosensing with Lipid-Functionalized Gold Nanorods. Journal of the American Chemical Society 2011, 133 (12) , 4182-4185.
    20. Aoune Barhoumi and Naomi J. Halas . Label-Free Detection of DNA Hybridization Using Surface Enhanced Raman Spectroscopy. Journal of the American Chemical Society 2010, 132 (37) , 12792-12793.
    21. Michael R. Rasch, Emma Rossinyol, Jose L. Hueso, Brian W. Goodfellow, Jordi Arbiol and Brian A. Korgel . Hydrophobic Gold Nanoparticle Self-Assembly with Phosphatidylcholine Lipid: Membrane-Loaded and Janus Vesicles. Nano Letters 2010, 10 (9) , 3733-3739.
    22. Mohan Babu Boggara and Ramanan Krishnamoorti. Small-Angle Neutron Scattering Studies of Phospholipid−NSAID Adducts. Langmuir 2010, 26 (8) , 5734-5745.
    23. Michael R. Rasch, Konstantin V. Sokolov and Brian A. Korgel . Limitations on the Optical Tunability of Small Diameter Gold Nanoshells. Langmuir 2009, 25 (19) , 11777-11785.
    24. Benjamin G. Janesko and Gustavo E. Scuseria. Molecule−Surface Orientational Averaging in Surface Enhanced Raman Optical Activity Spectroscopy. The Journal of Physical Chemistry C 2009, 113 (22) , 9445-9449.
    25. Hasan Hamedani, Hasan Kariminezhad, Hossein Amani. Photothermal Antibacterial Activity of Gold Nanorods Stabilized by Phospholipid. Brazilian Journal of Physics 2023, 53 (2)
    26. Nilesh Mathuria, Amber Lee R. Royal, Julia Enterría-Rosales, Yareli Carcamo-Bahena, Rossana Terracciano, Amish Dave, Miguel Valderrabano, Carly S. Filgueira. Near-infrared sensitive nanoparticle-mediated photothermal ablation of ventricular myocardium. Heart Rhythm 2022, 19 (9) , 1550-1556.
    27. Sara Gómez, Natalia Rojas-Valencia, Tommaso Giovannini, Albeiro Restrepo, Chiara Cappelli. Ring Vibrations to Sense Anionic Ibuprofen in Aqueous Solution as Revealed by Resonance Raman. Molecules 2022, 27 (2) , 442.
    28. Rossana Terracciano, Yareli Carcamo-Bahena, E. Brian Butler, Danilo Demarchi, Alessandro Grattoni, Carly S. Filgueira. Hyaluronate-Thiol Passivation Enhances Gold Nanoparticle Peritumoral Distribution When Administered Intratumorally in Lung Cancer. Biomedicines 2021, 9 (11) , 1561.
    29. Rossana Terracciano, Aobo Zhang, Mathieu L. Simeral, Danilo Demarchi, Jason H. Hafner, Carly S. Filgueira. Improvements in Gold Nanorod Biocompatibility with Sodium Dodecyl Sulfate Stabilization. Journal of Nanotheranostics 2021, 2 (3) , 157-173.
    30. Arvind Pandey, Veronica Vighetto, Nicola Di Marzio, Francesca Ferraro, Matteo Hirsch, Nicola Ferrante, Sankar Mitra, Alessandro Grattoni, Carly S. Filgueira. Gold Nanoparticles Radio-Sensitize and Reduce Cell Survival in Lewis Lung Carcinoma. Nanomaterials 2020, 10 (9) , 1717.
    31. Sajan D. George. Surface-Enhanced Raman Scattering Substrates: Fabrication, Properties, and Applications. 2020, 83-118.
    32. Takuma Makihara, Steven M. E. Demers, Louis E. D. Cole, Aobo Zhang, Jason H. Hafner. Thermophoresis of gold nanorods from surface enhanced Raman scattering and real-time Rayleigh scattering in solution. Analytical Methods 2019, 11 (18) , 2482-2488.
    33. Ashraf A. Aly, Alaa A. Hassan, El‐Shaimaa S. M. AbdEl‐latief. An Update of the Use of Thiocarbohydrazides and Thiosemicarbazides in the Preparation of Heterocycles and Their Biological Importance. Journal of Heterocyclic Chemistry 2018, 55 (10) , 2196-2223.
    34. Erika Aloi, Bruno Rizzuti, Rita Guzzi, Rosa Bartucci. Association of ibuprofen at the polar/apolar interface of lipid membranes. Archives of Biochemistry and Biophysics 2018, 654 , 77-84.
    35. Syeda Sara Hassan, Krista Carlson, Swomitra Kumar Mohanty, Sirajuddin, Ali Canlier. Ultra-rapid catalytic degradation of 4-nitrophenol with ionic liquid recoverable and reusable ibuprofen derived silver nanoparticles. Environmental Pollution 2018, 237 , 731-739.
    36. Petr Slepička, Jakub Siegel, Oleksiy Lyutakov, Nikola Slepičková Kasálková, Zdeňka Kolská, Lucie Bačáková, Václav Švorčík. Polymer nanostructures for bioapplications induced by laser treatment. Biotechnology Advances 2018, 36 (3) , 839-855.
    37. Hewen Li, Tao Zhao, Zhihua Sun. Analytical techniques and methods for study of drug-lipid membrane interactions. Reviews in Analytical Chemistry 2018, 37 (1)
    38. Wei Zhang, Lianmei Jiang, James A. Piper, Yuling Wang. SERS Nanotags and Their Applications in Biosensing and Bioimaging. Journal of Analysis and Testing 2018, 2 (1) , 26-44.
    39. Sirivipa Mongkolkitikul, Nophawan Paradee, Anuvat Sirivat. Electrically controlled release of ibuprofen from conductive poly(3-methoxydiphenylamine)/crosslinked pectin hydrogel. European Journal of Pharmaceutical Sciences 2018, 112 , 20-27.
    40. Ian Bruzas, William Lum, Zohre Gorunmez, Laura Sagle. Advances in surface-enhanced Raman spectroscopy (SERS) substrates for lipid and protein characterization: sensing and beyond. The Analyst 2018, 143 (17) , 3990-4008.
    41. S. L. Yefimova, T. N. Tkacheva, N. A. Kasian. Study of the Combined Effect of Ibuprofen and Cholesterol on the Microviscosity and Ordering of Model Lipid Membranes by Timeresolved Measurement of Fluorescence Anisotropy Decay. Journal of Applied Spectroscopy 2017, 84 (2) , 284-290.
    42. U. S. Dinish, Malini Olivo. SERS for Sensitive Biosensing and Imaging. 2017, 29-60.
    43. Mingwei Wan, Xiaoxu Li, Lianghui Gao, Weihai Fang. Self-assembly of gold nanorods coated with phospholipids: a coarse-grained molecular dynamics study. Nanotechnology 2016, 27 (46) , 465704.
    44. Desmond J. Hamilton, Yuheng Cai, Rupinder Kaur, Grant W. Marquart, Marilyn R. Mackiewicz, Scott M. Reed. Lipid-Coated Gold Nanoparticles as Probes for Membrane Binding. 2016, 1-16.
    45. Marek Prochazka. Biomolecular SERS Applications. 2016, 93-125.
    46. U. S. Dinish, Malini Olivo. SERS for Sensitive Biosensing and Imaging. 2015, 1-32.
    47. Alexey V. Krasnoslobodtsev, María P. Torres, Sukhwinder Kaur, Ivan V. Vlassiouk, Robert J. Lipert, Maneesh Jain, Surinder K. Batra, Yuri L. Lyubchenko. Nano-immunoassay with improved performance for detection of cancer biomarkers. Nanomedicine: Nanotechnology, Biology and Medicine 2015, 11 (1) , 167-173.
    48. Natália Mezzomo, Sibele R. Rosso Comim, Carlos E.M. Campos, Sandra R.S. Ferreira. Nanosizing of sodium ibuprofen by SAS method. Powder Technology 2015, 270 , 378-386.
    49. Xiao Cong He, Min Lin, Fei Li, Bao Yong Sha, Feng Xu, Zhi Guo Qu, Lin Wang. Advances in Studies of Nanoparticle–Biomembrane Interactions. Nanomedicine 2015, 10 (1) , 121-141.
    50. Beatriz B. Caravieri, Pollyanna F. de Oliveira, Ricardo A. Furtado, Denise C. Tavares, Eduardo J. Nassar, Katia J. Ciuffi, Eduardo F. Molina. Solubility enhancement of ibuprofen using tri-ureasil-PPO hybrid: structural, cytotoxic, and drug release investigation. Journal of Sol-Gel Science and Technology 2014, 72 (3) , 627-636.
    51. Andy Zapata-Escobar, Marcela Manrique-Moreno, Doris Guerra, C. Z. Hadad, Albeiro Restrepo. A combined experimental and computational study of the molecular interactions between anionic ibuprofen and water. The Journal of Chemical Physics 2014, 140 (18)
    52. Hector Ivan Melendez‐Ortiz, Patricia Díaz‐Rodríguez, Carmen Alvarez‐Lorenzo, Angel Concheiro, Emilio Bucio. Binary Graft Modification of Polypropylene for Anti‐Inflammatory Drug–Device Combo Products. Journal of Pharmaceutical Sciences 2014, 103 (4) , 1269-1277.
    53. Li-Ping Ye, Juan Hu, Li Liang, Chun-yang Zhang. Surface-enhanced Raman spectroscopy for simultaneous sensitive detection of multiple microRNAs in lung cancer cells. Chem. Commun. 2014, 50 (80) , 11883-11886.
    54. Wenpeng Yang, Yongjun Hu, Min Xie. Adsorption behavior of 6-Mercaptonicotinic acid on self-assembled gold nano-substrates explored by SERS combined with theoretical calculations. Journal of Colloid and Interface Science 2013, 408 , 151-156.
    55. Zulfiqar A. Tagar, Sirajuddin, Najma Memon, Muhammad S. Kalhoro, Paul O’Brien, Mohammad A. Malik, Mohammad I. Abro, Syeda S. Hassan, Nazar H. Kalwar, Yasmeen Junejo. Highly sensitive, selective and stable multi-metal ions sensor based on ibuprofen capped mercury nanoparticles. Sensors and Actuators B: Chemical 2012, 173 , 745-751.
    56. Syeda Sara Hassan, Sirajuddin, Amber Rehana Solangi, Tasneem Gul Kazi, Muhammad Siddique Kalhoro, Yasmeen Junejo, Zulfiqar Ali Tagar, Nazar Hussain Kalwar. Nafion stabilized ibuprofen–gold nanostructures modified screen printed electrode as arsenic(III) sensor. Journal of Electroanalytical Chemistry 2012, 682 , 77-82.
    57. Li-Xu WANG, Xiu-E JIANG. Bioanalytical Applications of Surface-enhanced Infrared Absorption Spectroscopy. Chinese Journal of Analytical Chemistry 2012, 40 (7) , 975-982.
    58. B. N. Khlebtsov, V. A. Khanadeev, E. V. Panfilova, S. A. Minaeva, M. Yu. Tsvetkov, V. N. Bagratashvili, N. G. Khlebtsov. Surface-enhanced raman scattering platforms on the basis of assembled gold nanorods. Nanotechnologies in Russia 2012, 7 (7-8) , 359-369.
    59. Lekun Liu, Hongwei Gao. Molecular structure and vibrational spectra of ibuprofen using density function theory calculations. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 2012, 89 , 201-209.
    60. Michael A. Ochsenkühn, Colin J. Campbell. Biomedical SERS Studies Using Nanoshells. 2012, 51-74.
    61. Philip Bartlett, Sumeet Mahajan. Raman Spectroscopy of Biomolecules at Electrode Surfaces. 2011, 269-334.
    62. Zulfiqar A. Tagar, Sirajuddin, Najma Memon, Muhammad H. Agheem, Yasmeen Junejo, Syeda S. Hassan, Nazar H. Kalwar, Manzoor I. Khattak. Selective, simple and economical lead sensor based on ibuprofen derived silver nanoparticles. Sensors and Actuators B: Chemical 2011, 157 (2) , 430-437.
    63. Zachary D. Schultz, Ira W. Levin. Vibrational Spectroscopy of Biomembranes. Annual Review of Analytical Chemistry 2011, 4 (1) , 343-366.
    64. Kyle C. Bantz, Audrey F. Meyer, Nathan J. Wittenberg, Hyungsoon Im, Özge Kurtuluş, Si Hoon Lee, Nathan C. Lindquist, Sang-Hyun Oh, Christy L. Haynes. Recent progress in SERS biosensing. Physical Chemistry Chemical Physics 2011, 13 (24) , 11551.
    65. Donald A. Perry, Hye Jin Son, James S. Cordova, Lauren G. Smith, Alexandru S. Biris. Adsorption analysis of nitrophenol isomers on silver nanostructures by surface-enhanced spectroscopy. Journal of Colloid and Interface Science 2010, 342 (2) , 311-319.
    66. Stephen D. Hudson, George Chumanov. Bioanalytical applications of SERS (surface-enhanced Raman spectroscopy). Analytical and Bioanalytical Chemistry 2009, 394 (3) , 679-686.
    67. Carly S. Levin, Janardan Kundu, Aoune Barhoumi, Naomi J. Halas. Nanoshell-based substrates for surface enhanced spectroscopic detection of biomolecules. The Analyst 2009, 134 (9) , 1745.
    68. Janardan Kundu, Carly S. Levin, Naomi J. Halas. Real-time monitoring of lipid transfer between vesicles and hybrid bilayers on Au nanoshells using surface enhanced Raman scattering (SERS). Nanoscale 2009, 1 (1) , 114.

    Pair your accounts.

    Export articles to Mendeley

    Get article recommendations from ACS based on references in your Mendeley library.

    Pair your accounts.

    Export articles to Mendeley

    Get article recommendations from ACS based on references in your Mendeley library.

    You’ve supercharged your research process with ACS and Mendeley!

    STEP 1:
    Click to create an ACS ID

    Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

    Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

    Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

    Your Mendeley pairing has expired. Please reconnect