Glenn A. Burley

Strategy for Conditional Orthogonal Sequential CuAAC Reactions Using a Protected Aromatic Ynamine

Co-reporter:Marine Z. C. Hatit, Ciaran P. Seath, Allan J. B. Watson, and Glenn A. Burley

The Journal of Organic Chemistry May 19, 2017 Volume 82(Issue 10) pp:5461-5461

Publication Date(Web):April 28, 2017

DOI:10.1021/acs.joc.7b00545

A method for conditional control of orthogonal sequential Cu-catalyzed azide−alkyne cycloaddition (CuAAC) reactions is reported. The inherent reactivity of an aromatic ynamine is controlled by a silyl protecting group that allows the selective CuAAC reaction of less reactive alkynes. Alternatively, the same protected ynamine undergoes selective CuAAC reaction via silyl deprotection in situ to give the ynamine click products. This allows complete orthogonal control of dialkyne systems and provides a unifying strategy for chemoselective CuAAC ligations in multialkyne/azide systems.

Modular, Step-Efficient Palladium-Catalyzed Cross-Coupling Strategy To Access C6-Heteroaryl 2-Aminopurine Ribonucleosides

Co-reporter:Helena S. Buchanan, Steven M. Pauff, Tilemachos D. Kosmidis, Andrea Taladriz-Sender, Olivia I. Rutherford, Marine Z. C. Hatit, Sabine Fenner, Allan J. B. Watson, and Glenn A. Burley

Organic Letters July 21, 2017 Volume 19(Issue 14) pp:3759-3759

Publication Date(Web):July 6, 2017

DOI:10.1021/acs.orglett.7b01602

Two Pd-catalyzed methods to access 6-heteroaryl 2-aminopurine ribonucleosides from 6-chloroguanosine are described. First, Pd-132-catalyzed Suzuki–Miyaura cross-coupling using a series of boron substrates and 6-chloroguanosine forms 6-heteroaryl-2-aminopurines in a single step. The versatility of 6-chloroguanosine is further demonstrated using a modified Sonogashira coupling employing potassium iodide as an additive. Finally, the utility of the 6-alkynyl-2-aminopurine ribonucleoside as a dipolarophile in [3 + 2] cycloadditions is presented, affording triazoles and isoxazoles when reacted with azide and isonitrile 1,3-dipoles, respectively.

Structural and Functional Basis of C-Methylation of Coumarin Scaffolds by NovO

Co-reporter:Joanna C. Sadler;Chun-wa H. Chung;Julie E. Mosley;Luke D. Humphreys

ACS Chemical Biology February 17, 2017 Volume 12(Issue 2) pp:374-379

Publication Date(Web):January 9, 2017

DOI:10.1021/acschembio.6b01053

C-methylation of aromatic small molecules by C-methyltransferases (C-MTs) is an important biological transformation that involves C–C bond formation using S-adenosyl-l-methionine (SAM) as the methyl donor. Here, two advances in the mechanistic understanding of C-methylation of the 8-position of coumarin substrates catalyzed by the C-MT NovO from Streptomyces spheroides are described. First, a crystal structure of NovO reveals the Arg116-Asn117 and His120-Arg121 motifs are essential for coumarin substrate binding. Second, the active-site His120 is responsible for deprotonation of the phenolic 7-hydroxyl group on the coumarin substrate, activating the rate-determining methyl transfer step from SAM. This work expands our mechanistic knowledge of C-MTs, which could be used in the downstream development of engineered biocatalysts for small molecule C-alkylations.

Synthetic biological approaches for RNA labelling and imaging: design principles and future opportunities

Co-reporter:Steven Pauff, Jamie M Withers, Iain JW McKean, Simon P Mackay, Glenn A Burley

Current Opinion in Biotechnology 2017 Volume 48(Volume 48) pp:

Publication Date(Web):1 December 2017

DOI:10.1016/j.copbio.2017.04.003

•Contemporary strategies for site-specific labelling of RNA are described.•Non-natural nucleotides offer opportunities to install functional groups at defined sites within RNA molecules.•Fluorogenic aptamer technology enables the visualization of unmodified RNA.•CRISPR-Cas9 technology enables direct imaging of RNA in cells, dispelling the need to engineer target RNA molecules.RNA is the most mercurial of all biomacromolecules. In contrast to DNA, where the predominant role is the storage of genetic information, the biological role of RNA varies; ranging from a template-based intermediary in gene expression to playing a direct role in catalysis. Their high turnover and metabolic lability makes the detection of specific sequences particularly challenging. This review describes the latest synthetic biological developments that enable the direct imaging of RNA both in vitro and in their native cellular environment.Download high-res image (61KB)Download full-size image

Transition-Metal-Free Amine Oxidation: A Chemoselective Strategy for the Late-Stage Formation of Lactams

Co-reporter:Robert J. Griffiths, Glenn A. BurleyEric P. A. Talbot

Organic Letters 2017 Volume 19(Issue 4) pp:

Publication Date(Web):February 8, 2017

DOI:10.1021/acs.orglett.7b00021

A metal-free strategy for the formation of lactams via selective oxidation of cyclic secondary and tertiary amines is described. Molecular iodine facilitates both chemoselective and regioselective oxidation of C–H bonds directly adjacent to a cyclic amine. The mild conditions, functional group tolerance, and substrate scope are demonstrated using a suite of diverse small molecule cyclic amines, including clinically approved drug scaffolds.

Reversible DNA micro-patterning using the fluorous effect

Co-reporter:Gabriella E. Flynn;Jamie M. Withers;Gerard Macias;Justin R. Sperling;Sarah L. Henry;Jonathan M. Cooper;Alasdair W. Clark

Chemical Communications 2017 vol. 53(Issue 21) pp:3094-3097

Publication Date(Web):2017/03/09

DOI:10.1039/C7CC00288B

We describe a new method for the immobilisation of DNA into defined patterns with sub-micron resolution, using the fluorous effect. The method is fully reversible via a simple solvent wash, allowing the patterning, regeneration and re-patterning of surfaces with no degradation in binding efficiency following multiple removal/attachment cycles of different DNA sequences.

Chemoselective Sequential Click Ligations Directed by Enhanced Reactivity of an Aromatic Ynamine

Co-reporter:Marine Z. C. Hatit, Joanna C. Sadler, Liam A. McLean, Benjamin C. Whitehurst, Ciaran P. Seath, Luke D. Humphreys, Robert J. Young, Allan J. B. Watson, and Glenn A. Burley

Organic Letters 2016 Volume 18(Issue 7) pp:1694-1697

Publication Date(Web):March 22, 2016

DOI:10.1021/acs.orglett.6b00635

Aromatic ynamines or N-alkynylheteroarenes are highly reactive alkyne components in Cu-catalyzed Huisgen [3 + 2] cycloaddition (“click”) reactions. This enhanced reactivity enables the chemoselective formation of 1,4-triazoles using the representative aromatic ynamine N-ethynylbenzimidazole in the presence of a competing aliphatic alkyne substrate. The unique chemoselectivity profile of N-ethynylbenzimidazole is further demonstrated by the sequential click ligation of a series of highly functionalized azides using a heterobifunctional diyne, dispelling the need for alkyne protecting groups.

DNA-directed spatial assembly of photosynthetic light-harvesting proteins

Co-reporter:Sarah L. Henry, Jamie M. Withers, Ishwar Singh, Jonathan M. Cooper, Alasdair W. Clark, Glenn A. Burley and Richard J. Cogdell

Organic & Biomolecular Chemistry 2016 vol. 14(Issue 4) pp:1359-1362

Publication Date(Web):09 Dec 2015

DOI:10.1039/C5OB02351C

This manuscript describes the surface immobilization of a light-harvesting complex to prescribed locations directed by the sequence-selective recognition of duplex DNA. An engineered light-harvesting complex (RC-LH1) derived from Rhodopseudomonas (Rps.) palustris containing the zinc finger (ZF) domain zif268 was prepared. The zif268 domain directed the binding of zfRC-LH1 to target double-stranded DNA sequences both in solution and when immobilized on lithographically defined micro-patterns. Excitation energy transfer from the carotenoids to the bacteriochlorophyll pigments within zfRC-LH1 confirmed that the functional and structural integrity of the complex is retained after surface immobilization.

SERS enhancement of silver nanoparticles prepared by a template-directed triazole ligand strategy

Co-reporter:Heba A. Kashmery, David G. Thompson, Ruggero Dondi, Samuel Mabbott, Duncan Graham, Alasdair W. Clark and Glenn A. Burley

Chemical Communications 2015 vol. 51(Issue 65) pp:13028-13031

Publication Date(Web):13 Jul 2015

DOI:10.1039/C5CC02883C

Two advances in the development of a one-pot method to prepare silver nanoparticles (AgNPs) using the Tollens' reagent are described. First, a template-directed process of AgNP synthesis using resorcinol triazole ligands bearing two pendent galactose sugars is shown. Second, the conversion of these AgNPs into SERS nanotags is demonstrated using malachite green isothiocyanate as the Raman reporter molecule.

Highly Efficient Synthesis of DNA-Binding Polyamides Using a Convergent Fragment-Based Approach

Co-reporter:Andrew J. Fallows, Ishwar Singh, Ruggero Dondi, Paul M. Cullis, and Glenn A. Burley

Organic Letters 2014 Volume 16(Issue 17) pp:4654-4657

Publication Date(Web):August 27, 2014

DOI:10.1021/ol502203y

Two advances in the synthesis of hairpin pyrrole-imidazole polyamides (PAs) are described. First, the application of a convergent synthetic strategy is shown, involving the Boc-based solid phase synthesis of a C-terminal fragment and the solution phase synthesis of the N-terminal fragment. Second a new hybrid resin is developed that allows for the preparation of hairpin PAs lacking a C-terminal β-alanine tail. Both methods are compatible with a range of coupling reagents and provide a facile, modular route to prepare PA libraries in high yield and crude purity.

Defining the Structural Parameters of Triazole Ligands in the Templated Synthesis of Silver Nanoparticles

Co-reporter:Heba A. Kashmery;Alasdair W. Clark;Ruggero Dondi;Andrew J. Fallows;Paul M. Cullis

European Journal of Inorganic Chemistry 2014 Volume 2014( Issue 28) pp:4886-4895

Publication Date(Web):

DOI:10.1002/ejic.201402593

Abstract

This manuscript describes a one-pot method for the synthesis of size- and shape-selected silver nanoparticles (AgNPs) using Tollens' reagent [Ag(NH₃)₂OH] as the silver source. Sugar triazole ligands facilitate the formation of monodisperse AgNPs in which the size and shape can be controlled according to the reaction conditions. Increasing the size of the ligand reduces size tunability but enhances colloidal stability in high-salt buffers. A key conclusion from this study is that the Ag^I-binding affinity of these triazole ligands determines their capacity to tune the size of the resultant AgNPs formed. Weaker Ag^I-binding ligands can be used to form monodisperse, angular AgNPs over a wider range of sizes [(12 ± 3) to (33 ± 7) nm], whereas triazole ligands that exhibit a higher Ag^I-binding affinity produce monodisperse, spherical AgNPs of a single size [(18 ± 5) nm].

An oligofluorene truxene based distributed feedback laser for biosensing applications

Co-reporter:Anne-Marie Haughey, Benoit Guilhabert, Alexander L Kanibolotsky, Peter J Skabara, Martin D Dawson, Glenn A Burley, Nicolas Laurand

Biosensors and Bioelectronics 2014 Volume 54() pp:679-686

Publication Date(Web):15 April 2014

DOI:10.1016/j.bios.2013.11.054

Highlights•Specific biosensing capabilities of a truxene-based DFB laser are demonstrated.•Functionalization of the laser sensor with a range of polyelectrolytes and biotin and subsequent avidin detection was investigated.•A lower avidin limit of detection of 1 g mL−1 was achieved.•Reversible avidin detection was demonstrated using a biotin analogue.The first example of an all-organic oligofluorene truxene based distributed feedback laser for the detection of a specific protein–small molecule interaction is reported. The protein avidin was detected down to 1μgmL−1 using our biotin-labelled biosensor platform. This interaction was both selective and reversible when biotin was replaced with desthiobiotin. Avidin detection was not perturbed by Bovine Serum Albumin up to 50,000μgmL−1. Our biosensor offers a new detection platform that is both highly sensitive, modular and potentially re-usable.

Sequence-Selective Detection of Double-Stranded DNA Sequences Using Pyrrole–Imidazole Polyamide Microarrays

Co-reporter:Ishwar Singh ; Christian Wendeln ; Alasdair W. Clark ; Jonathan M. Cooper ; Bart Jan Ravoo

Journal of the American Chemical Society 2013 Volume 135(Issue 9) pp:3449-3457

Publication Date(Web):February 4, 2013

DOI:10.1021/ja309677h

We describe a microarray format that can detect double-stranded DNA sequences with a high degree of sequence selectivity. Cyclooctyne-derivatized pyrrole–imidazole polyamides were immobilized on azide-modified glass substrates using microcontact printing and a strain-promoted azide–alkyne cycloaddition (SPAAC) reaction. These polyamide-immobilized substrates selectively detected a seven-base-pair binding site incorporated within a double-stranded oligodeoxyribonucleotide sequence even in the presence of an excess of a sequence with a single-base-pair mismatch.

Conjugation of PEG and gold nanoparticles to increase the accessibility and valency of tethered RNA splicing enhancers

Co-reporter:Andrew J. Perrett, Rachel L. Dickinson, Željka Krpetić, Mathias Brust, Helen Lewis, Ian C. Eperon and Glenn A. Burley

Chemical Science 2013 vol. 4(Issue 1) pp:257-265

Publication Date(Web):22 Oct 2012

DOI:10.1039/C2SC20937C

Since alternative splicing patterns are exhibited by most mammalian genes, the functional properties of a gene may be changed for therapeutic purposes by nudging splicing from one pattern to another. Splicing to a refractory exon can be enhanced using bifunctional targeted oligonucleotide enhancers of splicing (TOES), which anneal to a target exon and carry additional sequence motifs to recruit activator proteins. We have tested here the effectiveness of increasing the availability of the activating domain by using click chemistry to insert spacers of hexaethylene glycol (HEG) or abasic DNA between the activating and annealing domains of the oligonucleotide. We show that the presence of one or two HEG spacers can increase the effectiveness of an oligonucleotide, but the inclusion of 11 or 20 reduced the activity. To increase the valency of the oligonucleotides further, the annealing and activating domains were conjugated to gold nanoparticles (GNPs). We show that activity of these GNP–RNA conjugates in splicing assays depended on the size of the GNP conjugates, the RNA sequence and the directionality (i.e. attachment to GNP at either the 5′ or 3′-ends) of the RNA strands conjugated to the GNP surface. Strikingly, only the activating domains were required.

An organic semiconductor laser based on star-shaped truxene-core oligomers for refractive index sensing

Co-reporter:A.-M. Haughey, B. Guilhabert, A.L. Kanibolotsky, P.J. Skabara, G.A. Burley, M.D. Dawson, N. Laurand

Sensors and Actuators B: Chemical 2013 Volume 185() pp:132-139

Publication Date(Web):August 2013

DOI:10.1016/j.snb.2013.04.026

The sensing capabilities of an all-organic semiconductor distributed feedback laser based on star-shaped truxene-core molecules are described. Two assays are presented as a proof-of-principle demonstration. In the first, concentration changes in the range of 5–60% (v/v) glycerol solution in water were measured with a bulk detection sensitivity of 21 nm per refractive index unit. Secondly, layer-by-layer adsorption of polyelectrolytes to the laser surface, up to a thickness of ≈45 nm, was measured. The experimental results from both assays are compared to, and shown to agree with, a theoretical model. Organic semiconductor lasers of this type have a number of attractions including ease of large-scale fabrication, incorporation into existing assay equipment and no rigid optical alignment constraints for excitation and collection of emission, which makes them well-suited to sensing applications. Therefore, it is expected that this technology will be useful in biosensing applications where label-free samples are investigated.

Directed Assembly of DNA-Functionalized Gold Nanoparticles Using Pyrrole–Imidazole Polyamides

Co-reporter:Željka Krpetić ; Ishwar Singh ; Wu Su ; Luca Guerrini ; Karen Faulds ; Glenn A. Burley ;Duncan Graham

Journal of the American Chemical Society 2012 Volume 134(Issue 20) pp:8356-8359

Publication Date(Web):May 7, 2012

DOI:10.1021/ja3014924

Traditional methods for the construction of nanoparticle arrays and lattices exploit Watson–Crick base pairing of single-stranded DNA sequences as a proxy for self-assembly. Although this approach has been utilized in a variety of applications in nanoassembly, diagnostics, and biomedicine, the diversity of this recognition lexicon could be considerably increased by developing strategies that recognize the base-pairing landscape of double-stranded DNA (dsDNA) sequences. Herein we describe the first report of programmed gold nanoparticle (GNP) aggregation directed by the recognition of dsDNA sequences using pyrrole–imidazole polyamide–GNP (PA–GNP) conjugates. We demonstrate the reversibility and selectivity of this strategy for forming GNP aggregates in the presence of fully matched dsDNA sequences relative to dsDNA sequences containing one- and two-base-pair mismatches.

Orthogonal, metal-free surface modification by strain-promoted azide–alkyne and nitrile oxide–alkene/alkyne cycloadditions

Co-reporter:Christian Wendeln, Ishwar Singh, Stefan Rinnen, Christian Schulz, Heinrich F. Arlinghaus, Glenn A. Burley and Bart Jan Ravoo

Chemical Science 2012 vol. 3(Issue 8) pp:2479-2484

Publication Date(Web):13 Jun 2012

DOI:10.1039/C2SC20555F

In this article we present a fast and efficient methodology for biochemical surface patterning under extremely mild conditions. Micropatterned azide/benzaldoxime-surfaces were prepared by microcontact printing of a heterobifunctional cyclooctyne oxime linker on azide-terminated self-assembled monolayers (SAMs). Strain-promoted azide–alkyne cycloaddition (SPAAC) in combination with microcontact printing allows fast and effective surface patterning. The resulting bifunctional azide/oxime substrates could successfully be used for metal-free, orthogonal immobilization of various biomolecules by 1,3-dipolar cycloadditions at room temperature. Azide-decorated areas were modified by reaction with a cyclooctyne-conjugate using SPAAC, while benzaldoxime-decorated areas were activated by in situ oxidation to the reactive nitrile oxides and subsequent nitrile oxide cycloaddition with alkene- and alkyne-functionalized bioconjugates. In addition, orthogonal double immobilization was achieved by consecutive and independent SPAAC and nitrile oxide cycloadditions.

An RNA Splicing Enhancer that Does Not Act by Looping

Co-reporter:Helen Lewis;Andrew J. Perrett;Dr. Glenn A. Burley;Dr. Ian C. Eperon

Angewandte Chemie 2012 Volume 124( Issue 39) pp:9938-9941

Publication Date(Web):

DOI:10.1002/ange.201202932

Triazoles from N-Alkynylheterocycles and Their Coordination to Iridium

Co-reporter:Glenn A. Burley, Youcef Boutadla, David L. Davies, and Kuldip Singh

Organometallics 2012 Volume 31(Issue 3) pp:1112-1117

Publication Date(Web):January 25, 2012

DOI:10.1021/om201157g

N-alkynylheterocycles (benzimidazole and indazole) are converted to triazoles by click chemistry, and the resulting triazoles react with [IrCl2Cp*]2. The benzimidazole-triazole coordinates in a monodentate fashion through the benzimidazole, whereas the indazole-triazole is bidentate through coordination of both heterocycles. Reaction of the benzimidazole-triazole with methyliodide gives a benzimidazolium salt that deprotonates on coordination to afford a rare example of a bidentate NHC–triazole.

An RNA Splicing Enhancer that Does Not Act by Looping

Co-reporter:Helen Lewis;Andrew J. Perrett;Dr. Glenn A. Burley;Dr. Ian C. Eperon

Angewandte Chemie International Edition 2012 Volume 51( Issue 39) pp:9800-9803

Publication Date(Web):

DOI:10.1002/anie.201202932

DNA-Templated Photonic Arrays and Assemblies: Design Principles and Future Opportunities

Co-reporter:Dr. Wu Su;Dr. Vanessa Bonnard;Dr. Glenn A. Burley

Chemistry - A European Journal 2011 Volume 17( Issue 29) pp:7982-7991

Publication Date(Web):

DOI:10.1002/chem.201100924

Abstract

Molecular photonics is a rapidly developing and multi-disciplinary field of research involving the construction of molecular assemblies comprising photoactive building blocks that are responsive to a light stimulus. A salient challenge in this field is the controlled assembly of these building blocks with nanoscale precision. DNA exhibits considerable promise as an architecture for the templated assembly of photoactive materials. In this Concept Article we describe the progress that has been made in the area of DNA photonics, in which DNA acts as a platform for the construction of optoelectronic assemblies, thin films and devices.

Reversible DNA micro-patterning using the fluorous effect

Co-reporter:Gabriella E. Flynn, Jamie M. Withers, Gerard Macias, Justin R. Sperling, Sarah L. Henry, Jonathan M. Cooper, Glenn A. Burley and Alasdair W. Clark

Chemical Communications 2017 - vol. 53(Issue 21) pp:NaN3097-3097

Publication Date(Web):2017/02/23

DOI:10.1039/C7CC00288B

We describe a new method for the immobilisation of DNA into defined patterns with sub-micron resolution, using the fluorous effect. The method is fully reversible via a simple solvent wash, allowing the patterning, regeneration and re-patterning of surfaces with no degradation in binding efficiency following multiple removal/attachment cycles of different DNA sequences.

SERS enhancement of silver nanoparticles prepared by a template-directed triazole ligand strategy

Co-reporter:Heba A. Kashmery, David G. Thompson, Ruggero Dondi, Samuel Mabbott, Duncan Graham, Alasdair W. Clark and Glenn A. Burley

Chemical Communications 2015 - vol. 51(Issue 65) pp:NaN13031-13031

Publication Date(Web):2015/07/13

DOI:10.1039/C5CC02883C

Two advances in the development of a one-pot method to prepare silver nanoparticles (AgNPs) using the Tollens' reagent are described. First, a template-directed process of AgNP synthesis using resorcinol triazole ligands bearing two pendent galactose sugars is shown. Second, the conversion of these AgNPs into SERS nanotags is demonstrated using malachite green isothiocyanate as the Raman reporter molecule.

DNA-directed spatial assembly of photosynthetic light-harvesting proteins

Co-reporter:Sarah L. Henry, Jamie M. Withers, Ishwar Singh, Jonathan M. Cooper, Alasdair W. Clark, Glenn A. Burley and Richard J. Cogdell

Organic & Biomolecular Chemistry 2016 - vol. 14(Issue 4) pp:NaN1362-1362

Publication Date(Web):2015/12/09

DOI:10.1039/C5OB02351C

This manuscript describes the surface immobilization of a light-harvesting complex to prescribed locations directed by the sequence-selective recognition of duplex DNA. An engineered light-harvesting complex (RC-LH1) derived from Rhodopseudomonas (Rps.) palustris containing the zinc finger (ZF) domain zif268 was prepared. The zif268 domain directed the binding of zfRC-LH1 to target double-stranded DNA sequences both in solution and when immobilized on lithographically defined micro-patterns. Excitation energy transfer from the carotenoids to the bacteriochlorophyll pigments within zfRC-LH1 confirmed that the functional and structural integrity of the complex is retained after surface immobilization.

Conjugation of PEG and gold nanoparticles to increase the accessibility and valency of tethered RNA splicing enhancers

Co-reporter:Andrew J. Perrett, Rachel L. Dickinson, Željka Krpetić, Mathias Brust, Helen Lewis, Ian C. Eperon and Glenn A. Burley

Chemical Science (2010-Present) 2013 - vol. 4(Issue 1) pp:NaN265-265

Publication Date(Web):2012/10/22

DOI:10.1039/C2SC20937C

Since alternative splicing patterns are exhibited by most mammalian genes, the functional properties of a gene may be changed for therapeutic purposes by nudging splicing from one pattern to another. Splicing to a refractory exon can be enhanced using bifunctional targeted oligonucleotide enhancers of splicing (TOES), which anneal to a target exon and carry additional sequence motifs to recruit activator proteins. We have tested here the effectiveness of increasing the availability of the activating domain by using click chemistry to insert spacers of hexaethylene glycol (HEG) or abasic DNA between the activating and annealing domains of the oligonucleotide. We show that the presence of one or two HEG spacers can increase the effectiveness of an oligonucleotide, but the inclusion of 11 or 20 reduced the activity. To increase the valency of the oligonucleotides further, the annealing and activating domains were conjugated to gold nanoparticles (GNPs). We show that activity of these GNP–RNA conjugates in splicing assays depended on the size of the GNP conjugates, the RNA sequence and the directionality (i.e. attachment to GNP at either the 5′ or 3′-ends) of the RNA strands conjugated to the GNP surface. Strikingly, only the activating domains were required.

Orthogonal, metal-free surface modification by strain-promoted azide–alkyne and nitrile oxide–alkene/alkyne cycloadditions

Co-reporter:Christian Wendeln, Ishwar Singh, Stefan Rinnen, Christian Schulz, Heinrich F. Arlinghaus, Glenn A. Burley and Bart Jan Ravoo

Chemical Science (2010-Present) 2012 - vol. 3(Issue 8) pp:NaN2484-2484

Publication Date(Web):2012/06/13

DOI:10.1039/C2SC20555F

In this article we present a fast and efficient methodology for biochemical surface patterning under extremely mild conditions. Micropatterned azide/benzaldoxime-surfaces were prepared by microcontact printing of a heterobifunctional cyclooctyne oxime linker on azide-terminated self-assembled monolayers (SAMs). Strain-promoted azide–alkyne cycloaddition (SPAAC) in combination with microcontact printing allows fast and effective surface patterning. The resulting bifunctional azide/oxime substrates could successfully be used for metal-free, orthogonal immobilization of various biomolecules by 1,3-dipolar cycloadditions at room temperature. Azide-decorated areas were modified by reaction with a cyclooctyne-conjugate using SPAAC, while benzaldoxime-decorated areas were activated by in situ oxidation to the reactive nitrile oxides and subsequent nitrile oxide cycloaddition with alkene- and alkyne-functionalized bioconjugates. In addition, orthogonal double immobilization was achieved by consecutive and independent SPAAC and nitrile oxide cycloadditions.

TOPICS

Abstract

Abstract