The award in the Inorganic, Bioiinorganic and Organometallic Chemistry program in the Division of Chemistry and the Biomaterials program in the Division of Materials Research supports research by Professor Roger Kornberg at Stanford University to: 1) synthesize and perform X-ray crystal structures on gold nanoparticles, ranging in size from 1.5 to 3 nm; 2) analyze the chemical and physical properties of the gold-102 nanoparticle and additional nanoparticles; 3) conjugate these nanoparticles with proteins, DNA, and ligands of biological interest by procedures previously devised; and, 4) employ nanoparticle-scFv conjugates for the rapid structure determination of biological particles to near atomic resolution by cryo-electron microscopy, without a requirement for crystallization.
The intellectual merit of the proposed research lies in the contribution to the fundamental basis of nanochemistry. An application of particular interest for this proposal is the rapid structure determination to near atomic resolution of even very large, scarce biological particles.
The chief accomplishments of this research were the development of a large scale synthesis of Au102(p-MBA)44, the characterization of this compound by virtually all existing methods, and the development of the compound as a standard for cryo-electron microscopy. The intellectual merits lie in the validation of analytical methods and in the potential for enhancing structure determination of biological particles by cryo-electron microscopy. The analytical methods employed in the work include mass spectrometry, NMR, thermogravimetric analysis (TGA), optical absorption, electron microscopy (EM), and X-ray photoelectron spectroscopy (XPS). For use in electron microscopy, both conditions for conjugation with proteins and conditions for imaging have been established. The broader impacts of the work lie principally in the large scale synthesis of Au102(p-MBA)44, making this landmark compound available to the general scientific community. For the first time, all investigators interested in such compounds will have a molecule of of established three-dimensional structure as a point of reference. All research on large gold MPCs may be placed on a common footing. Electron microscopists, in particular, will have an imaging standard, which may be used as a label, as a basis for correction of microscope errors, and for image alignment and averaging. The eventual impact on electron microscopy may be profound.
