Nanoscale Multifunctional Molecules using DNA as scaffold
Lead Research Organisation:
University of Southampton
Department Name: Sch of Chemistry
Abstract
The design of functional entities of nanoscale dimensions has developed over the past 25 years into a fascinating, interdisciplinary field of ever growing interest. In contrast to the classical downscaling of physical components, upwards engineering to produce functional assemblies from chemical building blocks is most promising to meet the needs of future technologies. Supramolecular chemistry is one of the strategies which are currently under intense investigation to obtain functional molecules on the nanometre scale. Only very recently, DNA has become attractive as a supramolecular scaffold to produce nanoscaled entities. However, the double stranded DNA (dsDNA) has so far only been used because of its high selectivity in recognition through base-pairing to specifically connect nano particles, in DNA chip technology and nanolithography, to assemble arrays at surfaces, to create nanomechanical devices or to construct protein arrays and nanowires. Only few reports exist where the nucleobases themselves have been substituted to create a functional DNA.Porphyrins provide versatile building blocks in supramolecular chemistry due to their central metal binding site, their relative ease of functionalisation, and their characteristic photophysical and electrochemical properties. The latter can be tuned using appropriate substituents, central metals and ligands, which is required for an optimal interplay between different porphyrin units (i.e. energy or electron transfer). Thus, multiporphyrin arrays offer useful constructs for applications in almost all areas of science.This project aims to realise a modular building block system, in which structurally different porphyrins, and in different metallation states, are assembled onto a structurally predetermined backbone, and in a sequence specific manner, independent on the porphyrin structure. The idea is to use DNA as an acting template to assemble multiporphyrin systems. Nucleotides are substituted with porphyrins varying both in structure and metallation state to create a multifunctional molecule on the nanometre scale.We have now focused on the modification of deoxyuridine (dU), where we have established a general synthetic route to access both diphenyl and tetraphenyl porphyrin substituted dU. Changing the side chain on the porphyrin from a carboxylic ester to the corresponding carboxylates alters the solubility of the conjugate from being soluble in organic solvents to being soluble in aqueous solutions. The synthesis of dinucleotide-diporphyrin systems has shown that electronic interactions between the units occur. The solution phase synthesis, however, is not suitable to produce larger assemblies. We have therefore evaluated the use of standard solid phase chemistry using a DNA synthesiser to obtain homo- and hetero-porphyrinic tetranucleotide diporphyrin systems. Here, the absorption and emission spectroscopy measurements revealed electronic interactions between two different porphyrins when incorporated into the tetranucleotide, thus indicating the possibility to fine-tune the physical properties using our building block system.We have further been able to incorporate up to eleven porphyrins into a 21mer olgio-deoxynucleotide strand. First analytical data indicate an electronic interaction between the chromophores which does not occur when the porphyrins are measured as bulk material in organic solvents. A change in the structure towards an elongated helical structure can also be detected, together with a structure stabilisation in the single stranded porphyrin-DNA conjugate.The first data proof the concept, and the creation of a functional molecule on the nano-metre scale is possible using our strategy. The next stage is to get a detailed understanding of the physical properties of the construct. With this knowledge it will be possible to design the electronic wires that may lead to fundamentally new systems applicable in photovoltaics or computing.
Publications
Stulz E
(2017)
Nanoarchitectonics with Porphyrin Functionalized DNA.
in Accounts of chemical research
Stulz E
(2015)
Porphyrin-modified DNA as Construction Material in Supramolecular Chemistry and Nano-architectonics.
in Chimia
Brewer A
(2012)
Supramolecular hetero-porphyrin SWNT complexes
in Journal of Porphyrins and Phthalocyanines
Burns JR
(2011)
Directed formation of DNA nanoarrays through orthogonal self-assembly.
in Molecules (Basel, Switzerland)
Brewer A
(2011)
Introducing structural flexibility into porphyrin-DNA zipper arrays.
in Organic & biomolecular chemistry
Bandy TJ
(2011)
DNA as supramolecular scaffold for functional molecules: progress in DNA nanotechnology.
in Chemical Society reviews
Rühl T
(2010)
Synthesis of new building blocks for use in supramolecular DNA architectures
in Supramolecular Chemistry
McKee M
(2010)
Multistep DNA-Templated Reactions for the Synthesis of Functional Sequence Controlled Oligomers
in Angewandte Chemie
Nguyen T
(2009)
Duplex stabilization and energy transfer in zipper porphyrin-DNA.
in Angewandte Chemie (International ed. in English)
Nguyen T
(2009)
Duplex Stabilization and Energy Transfer in Zipper Porphyrin-DNA
in Angewandte Chemie
Description | We have explored DNA as a new construction material to create nanosized functional systems, which are promising in the fabrication of new optoelectronic devices. These can find application in next generation computers or in light-to-energy conversion. We are also investigating the use of modified DNA as therapeutics in cancer therapy. We have shown that synthetic DNA is much more than merely a biological template for life. The use of DNA, taken out of its natural context, can serve as a very versatile and predictable scaffold to create entirely new systems, which would be very difficult to obtain by conventional synthesis. This is a major step forward in DNA nanotechnology, and future applications will build on our results. |
Exploitation Route | The potential of the research is in the emerging field of nano-electronics and nano-medicine. Whilst we are exploring the constructs for potential use as electronic wires in new nano-sized molecular electronics, we have started to test some of the compounds actively as anticancer therapeutics, in particular in photodynamic therapy. Preliminary experiments have been very promising, and shown good cellular uptake of the porphyrin-DNA including killing of cancer cells using red light. |
Sectors | Chemicals,Electronics,Energy,Healthcare |
URL | http://www.southampton.ac.uk/~stulz/ |
Description | Peer Review Panel |
Geographic Reach | Asia |
Policy Influence Type | Membership of a guideline committee |
Impact | The peer review panel selects the proposals of highest impact for science and societal issues. |
Description | Steering committee |
Geographic Reach | Asia |
Policy Influence Type | Membership of a guideline committee |
Impact | The steering committee of Diamond Light Source has helped to improve the beamline B23 service and accessibility to both UK and international academic and industrial based researchers, who are working in health care, materials, biotechnology and energy/electronics. |
Description | Chemically Tagged DNA probes for sensing of DNA methylation biomarkers using Lab-on-a-chip |
Amount | £85,000 (GBP) |
Organisation | University of Southampton |
Sector | Academic/University |
Country | United Kingdom |
Start | 09/2012 |
End | 12/2016 |
Description | Determining surface oriented SRCD signatures of proteins on DNA origami tiles |
Amount | £90,000 (GBP) |
Organisation | Diamond Light Source |
Sector | Private |
Country | United Kingdom |
Start | 09/2016 |
End | 09/2019 |
Description | Development of a modular DNA-origami based cell targeting system for cancer therapy |
Amount | £90,000 (GBP) |
Organisation | University of Southampton |
Sector | Academic/University |
Country | United Kingdom |
Start | 09/2014 |
End | 09/2018 |
Description | Evaluation of a platform technology for manipulation of gene expression |
Amount | £20,000 (GBP) |
Organisation | Cancer Research UK |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 01/2016 |
End | 04/2016 |
Description | Functional DNA nanomaterials |
Amount | € 231,283 (EUR) |
Funding ID | FP7 MSCA-IEF NANO-DNA |
Organisation | European Commission |
Sector | Public |
Country | European Union (EU) |
Start | 09/2013 |
End | 09/2015 |
Description | B23 CD |
Organisation | Diamond Light Source |
Country | United Kingdom |
Sector | Private |
PI Contribution | Synthesis of modified DNA for high-end CD spectroscopy analysis using SRCD, data evaluation, writing of publications. |
Collaborator Contribution | Providing support in CD measurements using synchrotron based CD spectrometer, help in data evaluation and writing of publications. |
Impact | Multi-disciplinary projects, including synthetic chemistry, spectroscopy, biology and materials science. To date a total of 18 sessions were successfully applied for and obtained. Output: DOI: 10.1039/c5ob01681a DOI: 10.1039/c0ob00535e dx.doi.org/10.1002/anie.200805657 Theses: Porphyrin - DNA as a scaffold for nanoarchitecture and nanotechnology; TN. Nguyen, 2010 Supramolecular porphyrin arrays on DNA and SWNT scaffolds; A. J. Brewer, 2011 Functionalised DNA - Introducing & Applying a Versatile Porphyrin Molecular Ruler; J. R. Burns, 2011 Porphyrin substituted DNA: Building blocks for novel nanostructures; D. G. Singleton, 2012 The Structural Analysis of Porphyrin Modified DNA and the Construction of a Molecular Wire; J. W. Wood, 2015 |
Start Year | 2009 |
Description | B23 PhD |
Organisation | Diamond Light Source |
Country | United Kingdom |
Sector | Private |
PI Contribution | Design and synthesis of DNA origami platform for enzyme analysis; modifying enzymes with DNA; data acquisition and analysis; writing of publications. |
Collaborator Contribution | Support in data acquisition, data evaluation and writing of publications. Providing synchrotron based CD spectrometer. |
Impact | No outputs yet. Multi-disciplinary project involving organic chemistry, biology, spectroscopy and materials science. |
Start Year | 2016 |
Description | Cancer res Singapore |
Organisation | National Research Foundation Singapore |
Country | Singapore |
Sector | Charity/Non Profit |
PI Contribution | Development and synthesis of modified DNA origami nanopores, data evaluation, writing reports and publications. |
Collaborator Contribution | Performance of clinical trials towards specific targeting of cancer cells, data evaluation, help in writing publications. |
Impact | No outputs yet. Multidisciplinary project involving chemistry and medicine. |
Start Year | 2014 |
Description | DNA sensors |
Organisation | Polish Academy of Sciences |
Country | Poland |
Sector | Public |
PI Contribution | Collaboration in development of ultrasensitive DNA sensors. Our team is designing and synthesising the systems, and writing the publications. |
Collaborator Contribution | The partner institute is developing the sensors and performs measurements, and helps writing the publications. |
Impact | DOI: 10.1039/c4cc00172a. Deposition of Ni(II)Porphyrin Monolayer on the Gold Electrode via Azide-Alkyne Click - Coupling and its Electrochemical Characterization. |
Start Year | 2012 |
Description | Sensors Singapore |
Organisation | National Research Foundation Singapore |
Country | Singapore |
Sector | Charity/Non Profit |
PI Contribution | Providing modified DNA samples for the development of novel multisensors for cancer genes and cancer markers, data evaluation, writing publications. |
Collaborator Contribution | Development of sensors to detect early cancer markers from biological samples, data evaluation, help in writing publications. |
Impact | dx.doi.org/10.1016/j.bios.2014.05.017 Multi-disciplinary project involving chemistry and materials science (microfluidics). |
Start Year | 2012 |
Description | Supramolecular nanoscale arrays of fluorophores |
Form Of Engagement Activity | Participation in an open day or visit at my research institution |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Undergraduate students |
Results and Impact | Dissemination of results in form of poster presentation at the Southampton Nanofabrication Centre Open Day, Sept. 2009, Southampton. Discussions about potential future research collaborations. |
Year(s) Of Engagement Activity | 2009 |