NMR Study of Dendrimer Using Paramagnetic Cobalt(II) as a Probe
Inorganic Chemistry 1999, 38, 4498-4502.

Jon D. Epperson, Li-June Ming*, Barry D. Woosley, Gregory R. Baker, and George R. Newkome*
Department of Chemistry, the Institute for Biomolecular Science, and the Center for Molecular Design & Recognition, University of South Florida, Tampa, FL  33620

* To whom correspondence should be addressed.
L.-J. Ming  (813) 974-2220, ming@chuma.cas.usf.edu
G.R. Newkome  Telefax: Int. code (813) 974-4962, www.dendrimers.com

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    Cobalt(II) has been utilized as a paramagnetic 1H NMR probe to investigate the internal cavities of dendrimers possessing specifically located binding sites.  T1 values of the hyperfine-shifted signals were used to calculate metal-proton distances to build a molecular model of the internal structure of the dendrimers.  The presence of sizeable cavities within the dendrimers was observed including a loosely packed conformation for the 2,6-diaminopyridine moiety to bind to potential guest molecules.

    The unique supramolecular chemistry associated with dendritic macromolecules has raised great interest in the structural and chemical characteristics of these polymers.1   For example, the incorporation of specific recognition sites located within the dendritic structure has permitted chemical processes like H-bonding and metal ion complexation to occur at these loci.  Indeed, many dendrimers have been suggested to loosely mimic the structure and function of globular proteins owing to their large size, spherical shape, and specific host-guest chemistry.1b  Unlike proteins, however, dendrimers have not been successfully analyzed by X-ray crystallography due to their fractal nature that interrupts the long range molecular ordering necessary for crystal packing and X-ray diffraction.2   Dendrimers also exhibit broad overlapping 1H NMR features which further hinders the analysis of their conformations in solution.
    Paramagnetic metal ions with short electron relaxation times (<1011 s), especially Co(II), have been extensively used as intrinsic and external NMR probes for the analysis of the active sites of metalloproteins.3   Protons close to these paramagnetic metal centers can exhibit isotropically shifted (or hyperfine-shifted) 1H NMR signals with short relaxation times T1 and T2.3  These signals can be significantly shifted outside the crowded diamagnetic region at 0-10 ppm which facilitates their detection and assignment.  Presumably, isotropically shifted 1H NMR signals for paramagnetic metal-bound dendrimers, if detected, can be especially useful for the characterization of these macromolecules that exhibit poorly resolved overlapping 1H NMR features.  For example, a few dendrimers which contain intrinsic paramagnetic Fe-S cores have been shown to display some well-resolved hyperfine-shifted 1H NMR signals with small chemical shifts.4   For dendrimers lacking any intrinsic paramagnetic centers, simple paramagnetic metal ions such as Co(II) can be utilized as external probes for detailed investigation of the environment about metal recognition site(s), if present.  The availability of dendrimers possessing four potential metal binding 2,6-diamidopyridine sites5 affords a simple system to further evaluate this principle for the first time.  The diamidopyridine functional groups in these dendrimers have previously been demonstrated to be involved in H-bonding with guest molecules.5 Thus, these dendrimers may serve as prototypes for functional dendrimers.  We herein describe the use of the paramagnetic metal ion Co(II) as an external NMR probe for detailed investigation of dendrimer structure.
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(2) Ottaviani, M. F.; Bossmann, S.; Turro, N. J.; Tomalia, D. A. J. Am. Chem. Soc. 1994, 116, 661-671.
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(4)  a) Gorman, C. B.; Hager, M. W.; Parkhurst, B. L.; Smith, J. C. Macromolecules 1998, 31, 815-822.  b) Gorman, C. B.; Parkhurst, B. L.; Chen, K. Y.; Su, W. Y. J. Am. Chem. Soc. 1997, 119, 1141-1142.
(5)  a) Newkome, G. R.; Woosley, B. D.; He, E.; Moorefield, C. N.; Guther, R.; Baker, G. H.; Escamilla, G. H.; Merrill, J.; Luftmann, H. Chem. Commun. 1996, 2737-2738.  b) Breinlinger, E.; Niemz, A.; Rotello, V. M. J. Am Chem. Soc. 1995, 117, 5379-5380.

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