Showing papers on "Click chemistry published in 2005"

“On Water”: Unique Reactivity of Organic Compounds in Aqueous Suspension

Abstract: [*] Dr. S. Narayan, Dr. J. Muldoon, Prof. M. G. Finn, Prof. V. V. Fokin, Prof. H. C. Kolb, Prof. K. B. Sharpless Department of Chemistry and the Skaggs Institute of Chemical Biology The Scripps Research Institute 10550 North Torrey Pines Road La Jolla, CA 92037 (USA) Fax: (+ 1)619-554-6738 E-mail: sharples@scripps.edu [**] We thank Dr. Vladislav Litosh for carrying out preliminary work. Support from the National Institutes of Health, National Institute of General Medical Sciences (GM 28384), the National Science Foundation (CHE9985553), the Skaggs Institute for Chemical Biology, and the W. M. Keck Foundation is gratefully acknowledged. S.N. thanks the Skaggs Institute for a postdoctoral fellowship. We also thank Dr. Suresh Suri, Edwards Air Force Base, California, for a generous gift of quadricyclane. We urge our fellow chemists to float their problematic reactions on water and to send observations of success or failure to us at onwater@scripps.edu for public dissemination with attribution. Supporting information for this article is available on the WWW under http://www.angewandte.org or from the author. Angewandte Chemie

PEG- and peptide-grafted aliphatic polyesters by click chemistry.

Abstract: Novel aliphatic polyesters with pendent acetylene groups were prepared by controlled ring-opening polymerization and subsequently used for grafting poly(ethylene glycol) and oligopeptide moieties by the Cu(I)-catalyzed addition of azides and alkynes, a type of “click” chemistry. These aliphatic polyesters possess an acetylene graft density that can be tailored by ring-opening copolymerization of α-propargyl-δ-valerolactone (1) with e-caprolactone. Since the mild conditions associated with the click reaction are shown to be compatible with the polyester backbone, this method is a generally useful means for grafting numerous types of functionality onto aliphatic polyesters. The amphiphilic graft polyesters prepared in this study are shown to be biocompatible by in vitro cytotoxicity evaluation, suggesting their suitability for a range of biomaterial applications.

Structurally diverse dendritic libraries : A highly efficient functionalization approach using Click chemistry

Abstract: The high fidelity and efficiency of Click chemistry are exploited in the synthesis of a library of chain end functionalized dendritic macromolecules. In this example, the selectivity of the Cu-catalyzed [3 + 2π] cycloaddition reaction of azides with terminal acetylenes, coupled with mild reaction conditions, permits unprecedented functional group tolerance during the derivatization of dendrimeric and hyperbranched scaffolds. The resulting dendritic libraries are structurally diverse, encompassing a variety of backbones/surface functional groups, and are prepared in almost quantitative yields under very mild conditions. The robust and simple nature of this procedure, combined with its applicability to many aspects of polymer synthesis and materials chemistry, demonstrates an evolving synergy between advanced organic chemistry and functional materials.

Orthogonal Approaches to the Simultaneous and Cascade Functionalization of Macromolecules Using Click Chemistry

Abstract: The development of selective chemistries that are orthogonal to the diverse array of functional groups present in many polymeric systems is becoming an important tool for the synthesis and use of macromolecules in fields ranging from biomedical devices to nanotechnology. By combining copper-catalyzed cycloaddition chemistry with other synthetic transformations such as esterification, amidation, etc., highly efficient and modular simultaneous and cascade functionalization strategies have been developed. These single-step strategies for preparing multifunctional macromolecules represent a significant advance as compared to traditional multistep approaches, and the utility of these concepts is demonstrated by selective preparation of a diverse range of orthogonally functionalized vinyl polymers.

Shell click-crosslinked (SCC) nanoparticles: a new methodology for synthesis and orthogonal functionalization.

Abstract: A new methodology for the preparation of well-defined core-shell nanoparticles was developed, based upon the employment of a multifunctional crosslinker to coincidently stabilize supramolecular polymer assemblies and imbed into the shell unique chemical functionalities. Amphiphilic diblock copolymers of poly(acrylic acid)(80)-b-poly(styrene)(90) that had been assembled into micelles and partially functionalized throughout the corona with alkynyl groups were utilized as Click-readied nanoscaffolds for the formation of shell Click-crosslinked nanoparticles (SCCs). Divergently grown dendrimers of the zero, first, second, and third generations having increasing numbers of azide terminating groups ((N(3))(2)-[G-0], (N(3))(4)-[G-1], (N(3))(8)-[G-2], and (N(3))(16)-[G-3], respectively) were investigated as crosslinkers via Click reactions with the alkynyl groups to form covalent linkages throughout the block copolymer micelle corona, thus forming a crosslinked shell. The crosslinking reactions were characterized by (1)H NMR and IR spectroscopies, differential scanning calorimetry (DSC), and dynamic light scattering (DLS) measurements. Only the first generation dendrimer ((N(3))(4)-[G-1]) possessed a sufficient balance of polyvalency and water solubility to achieve crosslinking and establish a robust nanostructure. The resulting SCC was further characterized with atomic force microscopy (AFM), transmission electron microscopy (TEM), and analytical ultracentrifugation (AU). The dendritic crosslinker is important as it also allows for the incorporation of excess functionality that can undergo complementary reactions. Within the shell of this SCC the remaining azide termini of the dendrimer crosslinker were then consumed in a secondary Click reaction with an alkynyl-functionalized fluorescein to yield a fluorescently labeled SCC that was characterized with DLS, AFM, TEM, AU, UV-vis, and fluorescent measurements as a function of pH.

In situ selection of lead compounds by click chemistry: target-guided optimization of acetylcholinesterase inhibitors.

Abstract: The target-guided, in situ click chemistry approach to lead discovery has been successfully employed for discovering acetylcholinesterase (AChE) inhibitors by incubating a selected enzyme/tacrine azide combination with a variety of acetylene reagents that were not previously known to interact with the enzyme's peripheral binding site. The triazole products, formed by the enzyme, were identified by HPLC-mass spectrometry analysis of the crude reaction mixtures. The target-guided lead discovery search was also successful when performed with reagent mixtures containing up to 10 components. From 23 acetylene reagents, the enzyme selected two phenyltetrahydroisoquinoline (PIQ) building blocks that combined with the tacrine azide within the active center gorge to form multivalent inhibitors that simultaneously associate with the active and peripheral binding sites. These new inhibitors are up to 3 times as potent as our previous phenylphenanthridinium-derived compounds, and with dissociation constants as low as 33 femtomolar, they are the most potent noncovalent AChE inhibitors known. In addition, the new compounds lack a permanent positive charge and aniline groups and possess fewer fused aromatic rings. Remarkably, despite the high binding affinity, the enzyme displayed a surprisingly low preference for one PIQ enantiomer over the other.

Combining Atom Transfer Radical Polymerization and Click Chemistry: A Versatile Method for the Preparation of End-Functional Polymers

Abstract: Summary: The bromine chain ends of well-defined polystyrene ( = 2 700 g · mol−1, = 1.11) prepared using ATRP were successfully transformed into various functional end groups (ω-hydroxy, ω-carboxyl and ω-methyl-vinyl) by a two-step pathway: (1) substitution of the bromine terminal atom by an azide function and (2) 1,3-dipolar cycloaddition of the terminal azide and functional alkynes (propargyl alcohol, propiolic acid and 2-methyl-1-buten-3-yne). The “click” cycloaddition was catalyzed efficiently by the system copper bromide/4,4′-di-(5-nonyl)-2,2′-bipyridine. In all cases, 1H NMR spectra indicated quantitative transformation of the chain ends of polystyrene into the desired function. Preparation of well-defined functional polymers possessing diverse chain-end functionalities by the combination of atom transfer radical polymerization and click chemistry.

Functionalization of Micelles and Shell Cross-linked Nanoparticles Using Click Chemistry

Abstract: Shell cross-linked nanoparticles (SCKs) presenting Click-reactive functional groups in either the hydrophilic shell or the hydrophobic core region of block copolymer micelles in aqueous solution were synthesized by two routes. The first route utilized amidation chemistry to functionalize poly(acrylic acid) within the micelle shell with either azido or alkynyl groups. The second route employed latent functionality to introduce azido groups into the polystyrene core of the micelles. These Click-functionalized micelles were then cross-linked in an intramicellar fashion via amidation reactions within the shell layer to afford the SCKs bearing alkynyl groups in the shell or azido in the shell or core domains. The availability and reactivity of the functional groups in these nanoparticles toward Click chemistry was demonstrated by reaction with complementary Click-functionalized fluorescent dyes. The hydrodynamic diameters (Dh) of the micelles and nanoparticles were typically ca. 25 nm, as determined by dynamic...

Click Chemistry: Copper Clusters Catalyse the Cycloaddition of Azides with Terminal Alkynes

Abstract: Air-stable copper nanoclusters are good catalysts in the Cu(I)-catalysed “click” cycloaddition of azides with terminal alkynes to give 1,4-disubstituted 1,2,3-triazoles. No additional base or reducing agent is required. The reaction kinetics using various copper catalyst types and the function of copper particles in this system are studied and discussed.

Dendrimers Clicked Together Divergently

Abstract: Dendrimers containing 1,4-triazole linkages between each generation were grown divergently via the Click chemistry inspired Huisgen 1,3-dipolar cycloaddition reaction in the presence of a Cu(I) catalyst. The monomeric unit (1-propargylbenzene-3,5-dimethanol) contained the alkyne functionality, while the core (1,2-bis(2-azidoethoxy)ethane) and growing dendrimers presented the azide groups necessary for this type of Click reaction. The first generation dendrimer was also functionalized with alkyne termini to demonstrate an alternative pathway allowed by this chemistry. Synthesis and characterization, with infrared (IR), 1H and 13C NMR spectroscopies, high-resolution mass spectrometry, gel permeation chromatography (GPC), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA), are reported for these divergently grown dendrimers.

Click Chemistry as a Powerful Tool for the Construction of Functional Poly(p-phenyleneethynylene)s: Comparison of Pre- and Postfunctionalization Schemes

Abstract: 1,3-Dipolar cycloadditions have been used to prepare a series of functionalized poly(p-phenyleneethynylene)s (PPEs). This was accomplished by employing a PPE with pendent triisopropylsilylacetylene groups. The triisopropylsilyl groups can be removed in situ, exposing free alkynes in the side chains of the polymer to react with azides in a postpolymerization functionalization strategy in a 1,3-dipolar cycloaddition. The properties of these polymers were explored and compared to polymers of the same molecular structure but synthesized by a prepolymerization functionalization approach. Polymers of the same structure exhibit identical 1H NMR, 13C NMR, and IR spectra regardless of whether they were obtained by a conventional route or by postfunctionalization of a suitable PPE. UV−vis and fluorescence spectra are similar in solution. Postmodification through click chemistry, when compared to premodification, is an excellent method to produce functionalized, defect-free PPEs. Reaction of the azides with the main...

Efficient one-pot synthesis of 1,2,3-triazoles from benzyl and alkyl halides

Abstract: An efficient one-pot method for the preparation of 1,2,3-triazoles by 1,3-dipolar cycloaddition of in situ generated azides and alkynes is presented. This facile method can be applied to benzyl or alkyl halides and pure products are isolated by simple filtration.

Preparation of functional polymers

Abstract: The process of the present invention is directed toward conducting highly selective, high yield post polymerization reactions on polymers to prepare functionalized polymers. An embodiment of the present invention comprises conducting click chemistry reactions on polymers. Preferably, the polymers were prepared by controlled polymerization processes. Therefore, embodiments of the present invention comprise processes for the preparation of polymers comprising conducting a click chemistry reaction on a functional group attached to a polymer, wherein the polymer has a molecular weight distribution of less than 2.0. The functional polymers may be prepared by converting an attached functional unit on the polymer thereby providing site specific functional materials, site specific functional materials comprising additional functionality, or chain extended functional materials. Embodiments of the process of the present invention include functionalization reactions, chain extensions reactions, to form mock copolymer linking reactions, and attaching side chains to form graft copolymers, for example.

“Click chemistry”en route to pseudo-starch

Abstract: Rapid assembly of starch fragment analogues was achieved using “click chemistry”. Specifically, two hexadecasaccharide mimics containing two parallel maltoheptaosyl chains linked via [1,2,3]-triazoles to a maltose core were synthesized using Cu(I)-catalyzed [3 + 2] dipolar cycloaddition of azido saccharides and 6,6′- and 4′,6′-dipropargylated p-methoxyphenyl maltoside.