PROJECT GOALS AND OVERVIEW

   Dendrimers and hyperbranched polymers present unique opportunities to design sterically selective, chemoselective and enatioselective materials for molecular recognition. Recognition, however, is only the starting point to a more meaningful response. In order to take advantage of such materials, however, one needs a responsive center built into the core of the dendritic periphery capable of sensing or converting substrates that are brought into the dendrimer. Chemical agent capture, detection, and destruction are possible through the tailoring of the interior architecture of such dendrimers with catalytic or selective binding sites. Transition metal complexes with open coordination sites provide for a diversity of substrate bindings and catalytic transformations. Metal complexes provide the core reactivity both for new types of molecular sensors and for catalytic conversion. Specificity and stability of such complexes, however, often presents difficulties. The use of dendritic polymers to control access to an internal ligation or catalytic center has tremendous potential to provide supramolecular control of the reactivity of metal complexes, but has only recently been explored.

   Metalloporphyrins provide an especially attractive core for both dendrimer sensors and catalysts. The properties of metalloporphyrins are particularly well suited to their use both as oxidative catalysts and as substrate-binding detectors. Oxidative catalysis by metalloporphyrins is well established and originates from the facile formation of highly reactive metal-oxo (M=O) complexes from the reaction with various oxidants (RO₂H, H₂O₂, C₆H₅IO, O₂, ...). Such complexes are among the most reactive oxidants and in fact are also found in vivo in cytochrome P450, the heme protein responsible for most xenobiotic (drugs, poisons, misc. organics, ...) metabolism in the liver and kidneys. The use of metalloporphyrins as sensors is also well explored, and generally derives from their enormous extinction coefficients in the visible and the dramatic changes observed upon changes in metal ligation. In addition, the mechanism of many rapid poisons comes from binding to the five-coordinate heme of cytochrome oxidase (the terminal O₂ utilization enzyme), which makes the use of metalloporphyrin sensors particularly appropriate for the detection of chemical agents.

   Metalloporphyrins are a particularly versatile synthetic base upon which to assembly dendritic arrays. Both covalent linkage of dendrons to the ligand perimeter and self-assembly of hydrogen bonded dendrons to matching receptors built into the periphery of the metal complex are possible. The former approach has recently been explored by SUSLICK, in collaboration with MOORE, who recently demonstrated for the first time that shape selective oxidation of organic substrates can be achieved by attaching dendrimers to the periphery of metalloporphyrins [3]. Selection of the substrate on its steric or chemical properties are controlled by the dendritic substituents, while the oxidative reactivity is provided by the metal complex at the center of the polymer. The latter approach involves self-assembly of dendrons to the periphery of functionalized metalloporphyrins and builds on the recent advances by ZIMMERMAN. Other coordinatively unsaturated metal complexes (especially square planar complexes of salen type ligands and related chelates) may also be examined.

   Of special interest will be the use of combinatorial ensembles of dendritic or hyper-branched polymers with porphyrin cores. Combined with spatial resolution based on chromatographic separation, the development of a "olfactory optical detector" as an artificial nose derives from the large changes that occur in metalloporphyrins upon ligand binding. The use of combinatorial assembly of porphyrin-dendron (or hyper-branched polymer) systems from libraries of appropriate dendrons of the sort already prepared by FRECHET will be particularly interesting in the development of substrate specificity in both sensor and catalyst design. The development of microelectronic devises based on these combinatorial libraries of dendritic porphyrins will be done in collaboration with BEEBE.

PROPOSED RESEARCH

   We intend to further examine our recently synthesized new class of selective oxidation catalysts. These shape selective catalysts are based on the first oxidatively-robust dendrimer porphyrin complexes, and have been a successful collaboration merging the expertise of SUSLICK and MOORE [3]. A series of oxidatively robust poly(phenylesters) dendrimers were prepared through a convergent synthesis. Monodendrons were appended to the meta-positions of the 5, 10, 15, 20-tetrakis(3',5'-hydroxyphenyl) porphinato Mn(III) chloride to obtain a sterically protected metal center, as shown in the figures below. These complexes show a relatively high degree of shape selectivity for epoxidation and good oxidative stability.

   The shape selectivity of these catalysts was examined with both intra- and inter-molecular probes, as shown in the figure below. Selective epoxidation of non-conjugated dienes and of alkene mixtures of 1-alkenes and cyclooctene was catalyzed by dendrimer-metalloporphyrins using iodosylbenzene as the oxygen donor. The dendrimers exhibit significantly greater regioselectivity relative to the corresponding parent, manganese(III) tetraphenylporphyrin.

   To examine the extent of steric crowding around the porphyrin from the dendrimers, molecular modeling studies were performed on free-base porphyrin dendrimers. Although the top access is extremely limited in the dendrimer-metalloporphyrins, a significant side opening limits the extent of regioselectivity than can be achieved with meta-substitution of a tetraphenylporphyrin, as shown in the figure below. Current efforts are being made to put similar substituents in ortho positions of a tetra-aryl porphyrin. This will direct the dendrimer substituents in such a fashion as to prevent a side opening.

   Dendrimer porphyrins also provide an ideal class of compounds to use as optical sensors with diverse chemoselectivity due to their enormous extinction coefficients in the visible and the dramatic changes observed upon changes in metal ligation. A very wide range of important toxins bind strongly to metalloporphyrins, and the use of simple metalloporphyrins as sensors has been well explored. In addition, the mechanism of many rapid poisons comes from binding to the five-coordinate heme of cytochrome oxidase (the terminal O₂ utilization enzyme), which makes the use of metalloporphyrin sensors particularly appropriate for the detection of chemical agents.

   We are designing a multi-analyte optical sensor modeled on the olfactory system, in the sense that complex, time-dependent signals from spatially separated arrays of sensors provide a 'signature' of each analyte. In our system, a spatially resolved ensemble of dendritic metalloporphyrins provide spectral response patterns (e.g., spectral shifts, intensity changes, linewidth variations, and temporal responses) on exposure to organic vapors that depend on the physical and chemical nature (for example, polarity, shape and size) of the vapor. 'Artificial noses' of this type will be easy to assemble, eventually as an integral part of a single microelectronic device, and will have wide and important applications for toxin detection, environmental monitoring, and medical diagnostics.

   In particular, we are exploring the use of combinatorial ensembles of dendritic or hyper-branched polymers with porphyrin cores. A very wide range of possibilities exists here, including both covalent linkages and strongly hydrogen bonded self-assemblies (the latter in collaboration with ZIMMERMAN). The family of metals put into the core porphyrin is of equal importance to the range of dendrimer substituents. By varying the central metal, we can alter the range of hard/soft bases that will be bound. One may even prepare metalloporphyrin precursor complexes with a specific substrate already bound to the metal and then polymerize the hyperbranched polymer around it, thus generating a "molecular imprinting" within the dendrimer binding site.

Our intention is to combine a large family of various metalloporphyrin dendrimers (with both substituents and metal as variables) with a two-dimensional spatial resolution by thin-layer chromatograph.