title: Exploring possible mechanisms of action for the nanotoxicity and protein binding of decorated nanotubes: interpretation of physicochemical properties from optimal QSAR models.
abstract: Carbon nanotubes have become widely used in a variety of applications including biosensors and drug carriers. Therefore, the issue of carbon nanotube toxicity is increasingly an area of focus and concern. While previous studies have focused on the gross mechanisms of action relating to nanomaterials interacting with biological entities, this study proposes detailed mechanisms of action, relating to nanotoxicity, for a series of decorated (functionalized) carbon nanotube complexes based on previously reported QSAR models. Possible mechanisms of nanotoxicity for six endpoints (bovine serum albumin, carbonic anhydrase, chymotrypsin, hemoglobin along with cell viability and nitrogen oxide production) have been extracted from the corresponding optimized QSAR models. The molecular features relevant to each of the endpoint respective mechanism of action for the decorated nanotubes are also discussed. Based on the molecular information contained within the optimal QSAR models for each nanotoxicity endpoint, either the decorator attached to the nanotube is directly responsible for the expression of a particular activity, irrespective of the decorator's 3D-geometry and independent of the nanotube, or those decorators having structures that place the functional groups of the decorators as far as possible from the nanotube surface most strongly influence the biological activity. These molecular descriptors are further used to hypothesize specific interactions involved in the expression of each of the six biological endpoints.
authors.affiliation: exeResearch, LLC, 32 University Drive, East Lansing, MI 48823, USA; The Chem21 Group, Inc., 1780 Wilson Drive, Lake Forest, IL 60045, USA. Electronic address: emilio@exeResearch.com.
authors.forename: Emilio Xavier
authors.initials: EX
authors.lastname: Esposito
authors.affiliation: The Chem21 Group, Inc., 1780 Wilson Drive, Lake Forest, IL 60045, USA; College of Pharmacy MSC09 5360, 1 University of New Mexico, Albuquerque, NM, 87131, USA. Electronic address: hopfingr@gmail.com.
authors.forename: Anton J
authors.initials: AJ
authors.lastname: Hopfinger
authors.affiliation: Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, No. 1 Sec. 4, Roosevelt Road, Taipei 106, Taiwan.
authors.forename: Chi-Yu
authors.initials: CY
authors.lastname: Shao
authors.affiliation: Department of Computer Science and Information Engineering, National Taiwan University, No. 1 Sec. 4, Roosevelt Road, Taipei 106, Taiwan.
authors.forename: Bo-Han
authors.initials: BH
authors.lastname: Su
authors.affiliation: Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, No. 1 Sec. 4, Roosevelt Road, Taipei 106, Taiwan.
authors.forename: Sing-Zuo
authors.initials: SZ
authors.lastname: Chen
authors.affiliation: Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, No. 1 Sec. 4, Roosevelt Road, Taipei 106, Taiwan; Department of Computer Science and Information Engineering, National Taiwan University, No. 1 Sec. 4, Roosevelt Road, Taipei 106, Taiwan. Electronic address: yjtseng@csie.ntu.edu.tw.
authors.forename: Yufeng Jane
authors.initials: YJ
authors.lastname: Tseng
mesh_terms: D002256:Carbonic Anhydrases / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002918:Chymotrypsin / Q000378:metabolism; D006454:Hemoglobins / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015394:Molecular Structure; D037742:Nanotubes, Carbon / Q000737:chemistry / Q000633:toxicity*; D009569:Nitric Oxide / Q000378:metabolism; D011485:Protein Binding; D021281:Quantitative Structure-Activity Relationship; D018570:Risk Assessment; D012710:Serum Albumin, Bovine / Q000378:metabolism; D013499:Surface Properties
chemical_list: D006454:Hemoglobins; D037742:Nanotubes, Carbon; D012710:Serum Albumin, Bovine; D009569:Nitric Oxide; D002918:Chymotrypsin; D002256:Carbonic Anhydrases
keywords: Carbon nanotubes; Nanotoxicity; Nanotoxicity mechanism; Protein binding; QSAR