Article

Methyl groups of trimethylamine N-oxide orient away from hydrophobic interfaces.

Department of Chemistry, Texas A&M University, P.O. Box 30012, College Station, Texas 77843, USA.
Journal of the American Chemical Society (Impact Factor: 10.68). 10/2011; 133(46):18707-12. DOI: 10.1021/ja205106e
Source: PubMed

ABSTRACT The molecular orientation of trimethylamine N-oxide (TMAO), a powerful protein stabilizer, was explored at aqueous/hydrophobic interfaces using vibrational sum frequency spectroscopy (VSFS). The systems studied included the octadecyltrichlorosilane (OTS)/water interface, which represents an aqueous solution in direct contact with a hydrophobic medium. Surprisingly, the measurements revealed that the methyl groups of TMAO pointed into the aqueous phase and away from the OTS. This orientation may arise from the more hydrophilic nature of methyl groups attached to a strongly electron-withdrawing atom such as a quaternary nitrogen. Additional studies were performed at the air/water interface. This interface showed a high degree of TMAO alignment, but the dangling OH from water was present even at 5 M TAMO. Moreover, the addition of this osmolyte modestly increased the surface tension of the interface. This meant that this species was somewhat depleted at the interface compared to the bulk solution. These findings may have implications for the stabilizing effect of TMAO on proteins. Specifically, the strong hydration required for the methyl groups as well as the oxide moiety should be responsible for the osmolyte's depletion from hydrophobic/aqueous interfaces. Such depletion effects should help stabilize proteins in their folded and native conformations on entropic grounds, although orientational effects may play an additional role.

0 Bookmarks
 · 
152 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: The room temperature ionic liquid isopropylammonium formate (IPAF) is studied as a reversed phase HPLC mobile phase modifier for separation of native proteins using a polymeric column and the protein stability is compared to that using acetonitrile (MeCN) as the standard organic mobile phase modifier. A variety of important proteins with different numbers of subunits are investigated, including non-subunit proteins: albumin, and amyloglucosidase (AMY); a two subunit protein: thyroglobulin (THY); and four subunit proteins: glutamate dehydrogenase (GDH) and lactate dehydrogenase (LDH). A significant enhancement in protein stability is observed in the chromatograms upon using IPAF as a mobile phase modifier. The first sharper peak at about 2min represented protein in primarily the native form and a second broader peak more retained at about 5-6min represented substantially denatured or possibly aggregated protein. The investigated proteins (except LDH) could maintain the native form within up to 50% IPAF, while a mobile phase, with as low as 10% MeCN, induced protein denaturation. The assay for pyruvate using LDH has further shown that enzymatic activity can be maintained up to 30% IPAF in water in contrast to no activity using 30% MeCN.
    Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 08/2013; 940C:112-120. · 2.78 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: A new set of amphiphilic tertiary amine N-oxides has been prepared and their self-assembly properties observed in aqueous solution by tensiometry, dynamic and static light scattering. X-ray crystallographic analysis of parent amines and sulfoxide congeners indicates the formation of hydrogen-bonded dimers as the primary assembly unit for formation of vesicles in preference to the compact micelles typical of lauryl dimethylamine N-oxide (LDAO). 6-Benzyloxy-N,N'-bis(5-diethylaminopentylamine oxide)[1,3,5]triazine-2,4-diamine forms a 1 μm vesicle observed to entrap fluorescein. The [1,3,5]triazine core thus allows variation of the new self-assembled structures from nano- to micrometre length scales.
    ChemPhysChem 11/2013; · 3.35 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Selective oxidation of ω-tertiary amine self-assembled thiol monolayers to tertiary amine N-oxides is shown to transform the adhesion of model proteins lysozyme and fibrinogen upon them. Efficient preparation of both secondary and tertiary linker amides as judged by X-ray photoelectron spectroscopy (XPS) and water droplet contact angle was achieved with an improved amide bond formation on gold quartz crystal microbalance (QCM) sensors using 2-(1H-7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyl hexafluorophosphate methanaminium uronium (HATU). Oxidation with hydrogen peroxide was similarly assessed, and adhesion of lysozyme and fibrinogen from phosphate buffered saline was then assayed by QCM and imaged by AFM. Tertiary amine-functionalized sensors adsorbed multilayers of aggregated lysozyme, whereas tertiary amine N-oxides and triethylene glycol-terminated monolayers are consistent with small protein aggregates. The surface containing a dimethylamine N-oxide headgroup and ethyl secondary amide linker showed the largest difference in adsorption of both proteins. Oxidation of tertiary amine decorated surfaces therefore holds the potential for selective deposition of proteins and cells through masking and other patterning techniques.
    Langmuir 03/2013; 29(9):2961-70. · 4.38 Impact Factor

Full-text (2 Sources)

View
3 Downloads
Available from
Aug 5, 2014