Dendritech Inc.

Dendritic Nanotechnologies, Inc.

Michigan Molecular Institute

University of Michigan

Dow Corning Corporation

Douglas R Swanson

Donald A Tomalia

Rui Yin

Veera Reddy Pulgam

David M Hedstrand

Herbert M Brothers, Ii

Baohua Huang

James R Baker, Jr

Petar Radivoj Dvornic

Yong Hsu

Susan Victoria Perz

Michael James Owen

Roberta C Cheng

Abhay Singh Chauhan

Agnes M deLeuze-Jallouli

Ralph Spindler

Jolanta F Kukowska-Latallo

Cordell DeMattei

June W Klimash

Srinivas Uppuluri

Boahua Huang

Michael A Zhuravel

Lori A Reyna

Sonke Svenson

Joseph R Heinzelmann

Cordell R Demattei

Herbert M Ii Brothers

Dendritic polymers with enhanced amplification and interior functionality are disclosed. These dendritic polymers are made by use of fast, reactive ring-opening chemistry (or other fast reactions) combined with the use of branch cell reagents in a controlled way to rapidly and precisely build dendritic structures, generation by generation, with cleaner chemistry, often single products, lower excesses of reagents, lower levels of dilution, higher capacity method, more easily scaled to commercial dimensions, new ranges of materials, and lower cost. The dendritic compositions prepared have novel internal functionality, greater stability (e.g., thermal stability and less or no reverse Michael's reaction), and reach encapsulation surface densities at lower generations. Unexpectedly, these reactions of polyfunctional branch cell reagents with polyfunctional cores do not create cross-linked materials. Such dendritic polymers are useful as demulsifiers for oil/water emulsions, wet strength agents in the manufacture of paper, proton scavengers, polymers, nanoscale monomers, calibration standards for electron microscopy, making size selective membranes, and agents for modifying viscosity in aqueous formulations such as paint. When these dendritic polymers have a carried material associated with their surface and/or interior, then these dendritic polymers have additional properties for carrying materials due to the unique characteristics of the dendritic polymer, such as for drug delivery, transfection, and diagnostics.

Dendritic polymers with enhanced amplification and interior functionality

Poly(ester-acrylate) and poly(ester/epoxide) dendrimers. These materials can be synthesized by utilizing the so-called 'sterically induced stoichiometric' principles. The preparation of the dendrimers is carried out by reacting precursor amino/polyamino-functional core materials with various branch cell reagents. The branch cell reagents are dimensionally large, relative to the amino/polyamino-initiator core and when reacted, produce generation=1 dendrimers directly in one step. There is also a method by which the dendrimers can be stabilized and that method is the reaction of the dendrimers with surface reactive molecules to pacify the reactive groups on the dendrimers.

This invention provides a cost effective process and new Janus dendrimers where at least two dendrons are attached at the core (with or without a connector group) and where at least two of the dendrons have different functionality. Preferred are those Janus dendrimers where at least one dendron is a PEHAM dendron. Thus these Janus dendrimers are heterobifunctional in character and use unique ligation chemistry with single site functional dendrons, di-dendrons and multi-dendrons. Also included are Janus dendrons which may be used as intermediates to make the Janus dendrimers or to further react with another reactive moiety. These Janus dendrimers can provide several new dendrimer moieties, namely: combinatorial libraries of bifunctional structures; combined target director and signaling dendrimers; specific targeting entities for diagnostic and therapeutic applications, such as for example targeted MRI agents, targeted radionuclide delivery for diseases such as cancer, and targeted photosensitive or radiowave sensitive agents.

Janus dendrimers and dendrons

Core-shell tecto(dendrimers) useful in biomedicine, pharmaceuticals, personal care products, and in other ways analogous to the known uses for dendrimers, hypercomb branched polymers, and other dendritic polymers are the reaction product of a core dendritic polymer molecule having a plurality of terminal functional groups of a first type which are not reactive with each other, and a plurality of shell dendritic polymer molecules having a plurality of terminal functional groups of a second type which are not reactive with each other, but which are reactive with the terminal functional groups of the first type. Each of the shell dendritic polymer molecules is chemically bonded to the core dendritic polymer molecule by a reaction of at least one of the terminal functional groups of the second type with at least one of the terminal functional groups of the first type.

Core-shell tectodendrimers

Dendritic polymers containing disulfide functional groups which are essentially inert under non-reducing conditions, but which form sulfhydryl groups upon being subjected to a reducing agent are prepared by synthesizing dendritic polymers having a core with a disulfide linkage or by reacting a dendritic polymer with a molecule containing a disulfide linkage and reactive terminal groups. In one aspect of the invention, dendritic polymers having a single disulfide functional group at the core are provided. The single disulfide group at the core can be reduced to form two sulfhydryl groups to which other molecules, such as proteins, oligonucleotides, peptides, hormones, other dendritic polymers, non-dendritic polymers, etc., can be bound. Applications for the disulfide functionalized dendritic polymers include formation of differentiated dendrimers, formation of binding reagents for diagnostics, drug delivery, gene therapy and magnetic resins imaging, and in the preparation of self-assembled dendrimer monolayers on a quartz crystal resonators to provide dendrimer-modified electrodes which are useful for detecting various ions or molecules. In another aspect of the invention, dendritic polymers having sulfhydryl terminals are provided. The sulfhydryl terminated dendritic polymers can be used to prepare stable, curable resins composition which can undergo cross linking when subjected to a reducing agent.

Disulfide-containing dendritic polymers

A novel class of hyper comb-branched polymers conjugated with carried materials are disclosed.

Hyper comb-branched polymer conjugates

Radially layered copoly-dendrimers having unusual surface properties and novel applications have been synthesized and characterized. These are the first copolymeric dendrimers composed of a hydrophilic poly(amidoamine) (PAMAM) interior with hydrophobic organosilicon surfaces. These dendrimers have been prepared by surface modifications of an ethylene diamine core PAMAM dendrimer with (3-acryloxypropyl)methyldimethoxysilane, (3-acryloxypropyl)bis(vinyldimethylsiloxy)methylsilane, (3-acryloxypropyl)tris(trimethylsiloxy)silane, chloromethyltrimethylsilane, and chloromethyldimethylvinylsilane, to varying degrees of surface coverage. The obtained products were characterized by .sup.1 H, .sup.13 C, and .sup.29 Si NMR, and by DSC and TGA. The dendrimers with less completely covered organosilicon surfaces are water soluble, and have considerable surface activity, the best of which lowered the surface tension of water to less than 30 mN/m. Areas in their surface, according to the Gibbs adsorption isotherm, are surprisingly small, i.e., of the order of 100 .ANG..sup.2 /mol. More completely hydrophobed dendrimers are water insoluble, and form spread monolayers on water, capable of sustaining surface pressures over 40 mN/m. Areas per molecule are in the 1,000 .ANG..sup.2 /mol range.

Radially layered copoly (amidoamine-organosilicon) dendrimers

A novel process for preparing poly(2-isopropenyl-2-oxazoline or oxazine) and its methyl methacrylate copolymer, which are useful as water borne curing agents, particularly in the non-stick coating industry. The process converts commercially available poly(methyl methacrylate) into poly(2-isopropenyl-2-oxazoline or oxazine) polymers or copolymers with methyl methacrylate, while circumventing the use of the highly toxic monomer, 2-isopropenyl-2-oxazoline or oxazine. The process involves converting a poly(methacrylic ester) to the corresponding poly(.beta.-hydroxy-N-ethyl or propyl methacrylamide) and activating the ring-forming .beta.-hydroxy-N-ethyl or propyl methacrylamide moiety to form an oxazoline or oxazine ring.

Process for preparation of water borne curing agents

The specification discloses a process for producing poly-branched polymer having relatively high molecular weight by forming a first set of branches by polymerizing monomers which are either protected against or are non-reactive to branching and grafting during polymerization, grafting that first set of branches to a core having a plurality of reactive sites capable of reacting with the reactive end units of said branches, either deprotecting or activating a plurality of monomeric units on each of said branches to create branch reactive sites, forming a second set of branches in the same manner as the first set of branches were formed, grafting the second set of branches to the first set of branches by reacting the reactive end units of the second set of branches with each said branch reactive site on said first set of branches and repeating the foregoing steps reiteratively to form and attach subsequent sets of branches to prior branch sets until a desired number of iterations has been effected.

Process for producing hyper-comb-branched polymers

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Mt. Pleasant, MI, United States of America

Douglas R Swanson