[ { "id": "authors:xjq9y-zn524", "collection": "authors", "collection_id": "xjq9y-zn524", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20180309-071202119", "type": "book_section", "title": "Targeting DNA Mismatches with Coordination Complexes", "book_title": "DNA-targeting Molecules as Therapeutic Agents", "author": [ { "family_name": "Barton", "given_name": "Jacqueline K.", "orcid": "0000-0001-9883-1600", "clpid": "Barton-J-K" }, { "family_name": "Boynton", "given_name": "Adam N.", "orcid": "0000-0003-4427-513X", "clpid": "Boynton-Adam-Nathaniel" }, { "family_name": "Boyle", "given_name": "Kelsey M.", "orcid": "0000-0002-6728-8403", "clpid": "Boyle-Kelsey-M" } ], "contributor": [ { "family_name": "Waring", "given_name": "Michael J.", "clpid": "Waring-M-J" } ], "abstract": "DNA base pair mismatches occur naturally in cells as a result of incorporation errors and damage. Most cells are able to identify and correct these mistakes before replication, allowing for high genome fidelity between cellular generations. In some forms of cancer, however, proteins involved in the machinery of mismatch repair (MMR) undergo mutation, making those cells unable to correct mismatches and leading to an increase in mutations. Since higher mismatch frequency serves as an early indicator of cancer progression, for many researchers mismatches have provided a novel target for the design of organic and inorganic small-molecule therapeutics. In particular, transition metal complexes have shown great promise in this context owing to their valuable spectroscopic and photophysical properties and flexibility with respect to modification of their coordination spheres. Thus far, experimental designs have ranged from targeting the thermodynamic destabilization of mismatched sites to the hydrogen-bonding pattern of specific mismatched base pairs. Here, we review the diversity, practical application, and evolution of mismatch-targeting small molecules, with an emphasis on rhodium metalloinsertors and luminescent ruthenium compounds. Importantly, we highlight the discovery of metalloinsertion, a noncovalent DNA binding mode that is specific towards destabilized sites, such as mismatches, within the DNA duplex.", "doi": "10.1039/9781788012928-00367", "isbn": "978-1-78262-992-4", "publisher": "Royal Society of Chemistry", "place_of_publication": "Cambridge", "publication_date": "2018-03-12", "pages": "367-390" }, { "id": "authors:9adpm-m2130", "collection": "authors", "collection_id": "9adpm-m2130", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170705-093949953", "type": "book_section", "title": "Electrical Probes of DNA-Binding Proteins", "book_title": "DNA Repair Enzymes: Cell, Molecular, and Chemical Biology", "author": [ { "family_name": "Barton", "given_name": "Jacqueline K.", "orcid": "0000-0001-9883-1600", "clpid": "Barton-J-K" }, { "family_name": "Bartels", "given_name": "Phillip L.", "clpid": "Bartels-P-L" }, { "family_name": "Deng", "given_name": "Yingxin", "clpid": "Deng-Yingxin" }, { "family_name": "O'Brien", "given_name": "Elizabeth", "clpid": "O'Brien-Elizabeth" } ], "contributor": [ { "family_name": "Eichman", "given_name": "Brandt F.", "clpid": "Eichman-B-F" } ], "abstract": "A DNA electrochemistry platform has been developed to probe proteins bound to DNA electrically. Here gold electrodes are modified with thiol-modified DNA, and DNA charge transport chemistry is used to probe DNA binding and enzymatic reaction both with redox-silent and redox-active proteins. For redox-active proteins, the electrochemistry permits the determination of redox potentials in the DNA-bound form, where comparisons to DNA-free potentials can be made using graphite electrodes without DNA modification. Importantly, electrochemistry on the DNA-modified electrodes facilitates reaction under aqueous, physiological conditions with a sensitive electrical measurement of binding and activity.", "doi": "10.1016/bs.mie.2017.03.024", "pmcid": "PMC6314295", "isbn": "9780128118467", "publisher": "Academic Press", "place_of_publication": "San Diego, CA", "publication_date": "2017-05-10", "pages": "355-414" }, { "id": "authors:xjd2g-d8v37", "collection": "authors", "collection_id": "xjd2g-d8v37", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20210202-134852557", "type": "book_section", "title": "DNA Sensors Using DNA Charge Transport Chemistry", "book_title": "DNA in Supramolecular Chemistry and Nanotechnology", "author": [ { "family_name": "Barton", "given_name": "Jacqueline K.", "orcid": "0000-0001-9883-1600", "clpid": "Barton-J-K" }, { "family_name": "Furst", "given_name": "Ariel L.", "clpid": "Furst-Ariel-L" }, { "family_name": "Grodick", "given_name": "Michael A.", "orcid": "0000-0001-6618-6731", "clpid": "Grodick-Michael-A" } ], "contributor": [ { "family_name": "Stulz", "given_name": "Eugen", "clpid": "Stulz-Eugen" }, { "family_name": "Clever", "given_name": "Guido H.", "clpid": "Clever-Guido-H" } ], "abstract": "This chapter describes applications of DNA charge transport (DNA CT) in sensing, illustrating how this chemistry is used for the construction of sensitive devices for biochemical applications. It talks about the models for how this sensing technology might also be applied within the cell, how Nature may take advantage of DNA CT chemistry. Electrochemical devices utilizing DNA CT have evolved over time. The first DNA CT\u2010based detection platforms contained only a single electrode. DNA CT platforms are advantageous for the detection of proteins that interact with DNA. The chapter focuses on a variety of proteins that bind to DNA in different ways but which can all be detected sensitively using DNA electrochemistry. DNA CT can occur over long molecular distances, is sensitive to and can be modulated by DNA\u2010binding proteins, and reports electrically on the integrity of DNA. This chemistry can therefore be powerfully applied in sensing.", "doi": "10.1002/9781118696880.ch2.3", "isbn": "9781118696880", "publisher": "Wiley", "place_of_publication": "Chichester", "publication_date": "2014-12-23", "pages": "105-120" }, { "id": "authors:ph5p2-nms82", "collection": "authors", "collection_id": "ph5p2-nms82", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20160209-153402366", "type": "book_section", "title": "Probing Nucleic Acid Structure with Shape-Selective Rhodium and Ruthenium Complexes", "author": [ { "family_name": "Jackson", "given_name": "Brian A.", "clpid": "Jackson-B-A" }, { "family_name": "Barton", "given_name": "Jacqueline K.", "orcid": "0000-0001-9883-1600", "clpid": "Barton-J-K" } ], "abstract": "In this unit, transition metal complexes are used as photochemical probes for the structure of RNA and DNA. The transition metal ion provides a rigid substitutionally inert framework and an octahedral geometry for ligand coordination. The complexes can be constructed to define shapes, symmetries, and functionalities that complement those of the nucleic acid target. Complex formation is easily detected by light-induced nucleic acid cleavage. The modular construction of the complexes makes it possible to generate probes to examine a wide variety of structural characteristics of nucleic acids.", "doi": "10.1002/0471142700.nc0602s00", "publication_date": "2001-05-01" }, { "id": "authors:jcm4d-ct567", "collection": "authors", "collection_id": "jcm4d-ct567", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20160125-201652834", "type": "book_section", "title": "Radical migration through the DNA helix: chemistry at a distance", "book_title": "Interrelations Between Free Radicals and Metal Ions in Life Processes", "author": [ { "family_name": "Kelley", "given_name": "Shana O.", "orcid": "0000-0003-3360-5359", "clpid": "Kelley-S-O" }, { "family_name": "Barton", "given_name": "Jacqueline K.", "orcid": "0000-0001-9883-1600", "clpid": "Barton-J-K" } ], "contributor": [ { "family_name": "Sigel", "given_name": "Astrid", "clpid": "Sigel-A" }, { "family_name": "Sigel", "given_name": "Helmut", "clpid": "Sigel-H" } ], "abstract": "The reaction of the DNA bases with radical species generated by radiation, carcinogens, or oxidative stress can lead to mutagenic damage [1]. The efficiency and dynamics of radical transport through the DNA helix therefore hold profound biological implications. Intriguing questions concerning charge migration through DNA arise that can now begin to be addressed through well-defined chemical experiments. Does radical migration through DNA occur over long molecular distances? How is it modulated by DNA sequence and the structural variations in DNA? Is it physiologically important? How general is this phenomenon? These are issues that need to be addressed in the context of delineating mechanisms of DNA damage and repair.", "isbn": "9780824719562", "publisher": "Marcel Dekker", "place_of_publication": "New York, NY", "publication_date": "1999-03-10", "pages": "211-249" }, { "id": "authors:qf7yk-rzg69", "collection": "authors", "collection_id": "qf7yk-rzg69", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20180406-080327207", "type": "book_section", "title": "Metallointercalators as Probes of the DNA \u03c0-way", "book_title": "Mechanistic Bioinorganic Chemistry", "author": [ { "family_name": "Arkin", "given_name": "Michelle R.", "clpid": "Arkin-M-R" }, { "family_name": "Jenkins", "given_name": "Yonchu", "clpid": "Jenkins-Y" }, { "family_name": "Murphy", "given_name": "Catherine J.", "clpid": "Murphy-C-J" }, { "family_name": "Turro", "given_name": "Nicholas J.", "clpid": "Turro-N-J" }, { "family_name": "Barton", "given_name": "Jacqueline K.", "orcid": "0000-0001-9883-1600", "clpid": "Barton-J-K" } ], "abstract": "This chapter describes efforts in our laboratory to characterize the role of double helical DNA in catalyzing electron-transfer reactions. Using intercalating metal complexes as donor and acceptor, we have shown that the luminescence of [Ru(phen)_2(dppz)]^(2+*) is efficiently quenched by [Rh(phi)_2(phen)]^(3+) in the presence of B-form DNA. Covalent attachment of these metal complexes to either ends of a short duplex leads to complete quenching of luminescence over a separation distance between intercalated donor and acceptor of >40\u00c5. These results with metallointercalators point to the \u03c0-stacked array of heterocyclic DNA base pairs as an effective intervening medium for long-range electron transfer and provides a new approach in applying the DNA helical polymer as a \"molecular wire.\"", "doi": "10.1021/ba-1995-0246.ch017", "isbn": "9780841230620", "publisher": "American Chemical Society", "place_of_publication": "Washington, DC", "publication_date": "1996-05-05", "pages": "449-469" }, { "id": "authors:ps8q0-3hg85", "collection": "authors", "collection_id": "ps8q0-3hg85", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20201120-120817888", "type": "book_section", "title": "Time resolved electron transfer studies between metallointercalators in DNA", "book_title": "Ultrafast Phenomena X", "author": [ { "family_name": "H\u00f6rmann", "given_name": "A.", "clpid": "H\u00f6rmann-A" }, { "family_name": "Olson", "given_name": "E. J. C.", "clpid": "Olson-E-J-C" }, { "family_name": "Barbara", "given_name": "P. F.", "clpid": "Barbara-P-F" }, { "family_name": "Arkin", "given_name": "M. R.", "clpid": "Arkin-M-R" }, { "family_name": "Stemp", "given_name": "E. D. A.", "orcid": "0000-0003-2098-4214", "clpid": "Stemp-E-D-A" }, { "family_name": "Holmlin", "given_name": "R. E.", "clpid": "Holmlin-R-E" }, { "family_name": "Barton", "given_name": "J. K.", "orcid": "0000-0001-9883-1600", "clpid": "Barton-J-K" } ], "contributor": [ { "family_name": "Barbara", "given_name": "Paul F.", "clpid": "Barbara-P-F" }, { "family_name": "Fujimoto", "given_name": "James G.", "clpid": "Fujimoto-James-G" }, { "family_name": "Knox", "given_name": "Wayne H.", "clpid": "Knox-W-H" }, { "family_name": "Zinth", "given_name": "Wolfgang", "clpid": "Zinth-W" } ], "abstract": "Ultrafast studies on the rates of DNA-mediated forward and reverse electron transfer between photoexcited [Ru(phen)\u2082dppz]\u00b2\u207a and various acceptors are reported. We also present the first results that resolve the ultrafast emission decay of the so-called \"light-switch\" molecule [Ru(phen)\u2082dppz]\u00b2\u207a in aqueous solution, distinguishing the diverse photophysical mechanisms of [Ru(phen)\u2082dppz]\u00b2\u207a.", "doi": "10.1007/978-3-642-80314-7_157", "isbn": "9783642803161", "publisher": "Springer Berlin Heidelberg", "place_of_publication": "Berlin, Heidelberg", "publication_date": "1996", "pages": "359-360" }, { "id": "authors:v4dfz-x9q33", "collection": "authors", "collection_id": "v4dfz-x9q33", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20160126-112520082", "type": "book_section", "title": "DNA photofootprinting with Rh(phi)_2bpy^(3+)", "book_title": "Protocols for Gene Analysis", "author": [ { "family_name": "Klakamp", "given_name": "Scott L.", "clpid": "Klakamp-S-L" }, { "family_name": "Barton", "given_name": "Jacqueline K.", "orcid": "0000-0001-9883-1600", "clpid": "Barton-J-K" } ], "contributor": [ { "family_name": "Harwood", "given_name": "A. J.", "clpid": "Harwood-A-J" } ], "abstract": "This chapter describes one method for high resolution photofootprinting of proteins or small drugs bound to DNA (1). DNA footprinting is an electrophoretic method that permits the visualization (footprint) of the binding site of a molecule site-specifically bound to DNA. The method entails the nonspecific cleavage of a radioactively end-labeled DNA containing the site-specifically bound molecule. Protection from this sequence neutral cleavage at the binding site reveals the footprint. Photofootprinting differs from other conventional footprinting techniques in that DNA cleavage occurs directly on irradiation of a photocleaving reagent, which binds to the target DNA sequence. Alternative photofootprinting methods produce DNA cleavage indirectly by creating photo-damaged DNA adducts that are labile to base treatment after irradiation of the DNA (2,3). Traditional footprinting procedures utilize either a protein like DNase I for cleavage or small molecule reagents that cleave DNA under specific chemical conditions (4\u20138).", "doi": "10.1385/0-89603-258-2:331", "isbn": "978-0-89603-258-3", "publisher": "Humana Press", "place_of_publication": "Totowa, NJ", "publication_date": "1994", "pages": "331-338" }, { "id": "authors:zhqr2-7n273", "collection": "authors", "collection_id": "zhqr2-7n273", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20161018-141749842", "type": "book_section", "title": "How to make a molecular light switch sequence-specific: tethering of an oligonucleotide to a dipyridophenazine complex of ruthenium (II)", "book_title": "Advances in Fluorescence Sensing Technology", "author": [ { "family_name": "Jenkins", "given_name": "Yonchu", "clpid": "Jenkins-Y" }, { "family_name": "Barton", "given_name": "Jacqueline", "orcid": "0000-0001-9883-1600", "clpid": "Barton-J-K" } ], "contributor": [ { "family_name": "Lakowicz", "given_name": "Joseph R.", "clpid": "Lakowicz-J-R" }, { "family_name": "Thompson", "given_name": "Richard B.", "clpid": "Thompson-R-B" } ], "abstract": "Considerable attention has been given recently to the design and development of nonradiative methods of recognizing DNA in a sequence-specific manner. Earlier, we reported that Ru(bpy)_2dppz^(2+)(bpy equals 2,2'-bipyridine, dppz equals dipyrido[3,2:a-2',3':c]phenazine) shows no luminescence in aqueous solution, but upon intercalation into double-helical DNA, bright photoluminescence is observed (A. E. Friedman, et al., J. Am. Chem. Soc., 1990, 112, 4960). Based upon this observation, a sequence-specific molecular light switch has been designed in which a dppz complex of ruthenium(II) is tethered onto an oligonucleotide. An oligonucleotide modified at its 5 foot end has been constructed by coupling the sequence 5'-H_2N(CH_2)_6AGTGCCAAGCTTGCA-3' to Ru(phen')_2dppz^(2+) (phen' equals 5-amido-glutaric acid-1,10-phenanthroline). Like the parent complex Ru(bpy)_2dppz^(2+), the single-stranded metal-oligonucleotide conjugate shows little detectable luminescence in aqueous solution. Addition of the complementary strand results in intense photoluminescence; time-resolved studies show that the emission is biphasic with excited state lifetimes of 500 (60%) and 110 (40%) ns. As expected, addition of a non- complementary strand produces no luminescence enhancement over that of the single-stranded metal-oligonucleotide. These results demonstrate that this oligonucleotide derivatized metal complex can be used to recognize and target specific sequences on DNA, a valuable feature which may lead to interesting and novel applications in hybridization technology.", "doi": "10.1117/12.144704", "isbn": "9780819411129", "publisher": "Society of Photo-Optical Instrumentation Engineers", "place_of_publication": "Bellingham, WA", "publication_date": "1993-05-18", "pages": "129-137" }, { "id": "authors:kc34b-fx877", "collection": "authors", "collection_id": "kc34b-fx877", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20160308-093657057", "type": "book_section", "title": "Ruthenium complexes as luminescent reporters of DNA", "book_title": "Metallobiochemistry Part C: Spectroscopic and Physical Methods for Probing Metal Ion Environments in Metalloenzymes and Metalloproteins", "author": [ { "family_name": "Murphy", "given_name": "Catherine J.", "clpid": "Murphy-C-J" }, { "family_name": "Barton", "given_name": "Jacqueline K.", "orcid": "0000-0001-9883-1600", "clpid": "Barton-J-K" } ], "contributor": [ { "family_name": "Riordan", "given_name": "James F.", "clpid": "Riordan-J-F" }, { "family_name": "Vallee", "given_name": "Bert L.", "clpid": "Vallee-B-L" } ], "abstract": "Coordination chemistry provides a wealth of characteristics that may be exploited in probing nucleic acids. Structurally and stereochemically well-defined transition metal complexes have been designed to probe nucleic acid structure and the recognition process. Reactive transition metal complexes have been tethered onto DNA-binding moieties to report sensitively on their recognition characteristics. This chapter discusses coordination complexes that have been remarkably useful as spectroscopic tags. In particular, it describes the application of ruthenium complexes to probe nucleic acid structure and recognition. Polypyridyl complexes of ruthenium(II) and their derivatives possess several features that may be exploited in developing spectroscopic probes for nucleic acids. The complexes possess an intense metal-toligand charge transfer (MLCT) transition in the visible region which yields a luminscent excited state; the excited state characteristics of these complexes have been amply characterized. Most importantly, this transition is perturbed on binding to DNA. The complexes are coordinatively saturated. They are inert to substitution and are stable in aqueous solution. Because the complexes are octahedral and possess three bidentate ligands, the complexes are chiral.", "doi": "10.1016/0076-6879(93)26027-7", "isbn": "9780121821272", "publisher": "Academic Press", "place_of_publication": "San Diego, CA", "publication_date": "1993", "pages": "576-594" }, { "id": "authors:at4ef-y2x87", "collection": "authors", "collection_id": "at4ef-y2x87", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20160307-150932721", "type": "book_section", "title": "Transition metal complexes as probes of nucleic acids", "book_title": "DNA Structures Part B: Chemical and Electrophoretic Analysis of DNA", "author": [ { "family_name": "Chow", "given_name": "Christine S.", "clpid": "Chow-Christine-S" }, { "family_name": "Barton", "given_name": "Jacqueline K.", "orcid": "0000-0001-9883-1600", "clpid": "Barton-J-K" } ], "contributor": [ { "family_name": "Lilley", "given_name": "David M. J.", "clpid": "Lilley-D-M-J" }, { "family_name": "Dahlberg", "given_name": "James E.", "clpid": "Dahlberg-J-E" } ], "abstract": "This chapter discusses a series of transition metal complexes that recognize the nucleic acid binding sites based on shape selection. By matching the shapes and symmetries of the metal complexes to particular variations in local nucleic acid conformation, a family of molecules that target different DNA sites have been developed. The recognition of a site depends on the local conformation, or shape, rather than on the sequence directly. Indeed, based purely on such considerations of shape and symmetry, a high level of specificity may be achieved. The molecules prepared serve as a novel series of conformation-selective probes, and these may be utilized to map the topological variations in structure along the nucleic acid polymer. The chapter also discusses the sequence-neutral cleavage complex, Rh(phi)^2bpy^(3+) (where bpy is bipyridine), a useful reagent for high-resolution photofootprinting, as well as several conformation specific tools to examine nucleic acid structure. These various ruthenium and rhodium complexes may be applied to detect subtle variations in B-DNA conformations or to investigate global secondary structures of a polynucleotide such as DNA cruciforms, left-handed Z-DNA, and A-form DNA. The chapter describes the way the secondary and tertiary structure of RNA may be examined using this methodology. The different information that may be gained from these methods is also discussed. In general, studies with these complexes provide a unique and sensitive handle to probe elements of nucleic acid polymorphism in solution.", "doi": "10.1016/0076-6879(92)12014-H", "isbn": "9780121821135", "publisher": "Academic Press", "place_of_publication": "San Diego, CA", "publication_date": "1992", "pages": "219-242" }, { "id": "authors:eczrc-fjj24", "collection": "authors", "collection_id": "eczrc-fjj24", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20201111-190742675", "type": "book_section", "title": "Photoelectron transfer between molecules adsorbed in restricted spaces", "book_title": "Photochemical Conversion and Storage of Solar Energy", "author": [ { "family_name": "Turro", "given_name": "Nicholas J.", "clpid": "Turro-N-J" }, { "family_name": "Barton", "given_name": "Jacqueline K.", "orcid": "0000-0001-9883-1600", "clpid": "Barton-J-K" }, { "family_name": "Tomalia", "given_name": "Donald", "clpid": "Tomalia-D-A" } ], "contributor": [ { "family_name": "Pelizzetti", "given_name": "E.", "clpid": "Pelizzetti-E" }, { "family_name": "Schiavello", "given_name": "M.", "clpid": "Schiavello-M" } ], "abstract": "The photophysics and photoelectron transfer reactions of metal complexes bound to anionic surfaces which provide restricted spaces in aqueous solutions have been investigated by steady state and time resolved luminescence spectroscopy. The electron transfer systems were generated by systematically variation of structures derived from the Ru (II) tris-bipyridyl family as electron donors and methyl viologens and other metal tris-bipyridyl complexes as electron acceptors. The structure of the bipyridyl ligand in the complex was varied with respect to its functionality, size and shape in order to provide electron donors of similar driving force for electron transfer, but of differing binding selectivity and dynamics. In the same vein, metal substitution, e.g., Co (III) for Ru (II), provides a family of acceptors whose structures may be readily varied systematically. In addition, the inherent chirality of the tris-bipyridyl complexes allows opportunities for investigation of enantiomeric selection in binding and in the electron transfer step. The anionic surfaces selected for these investigations include those provided by micelles polyelectrolyte polymers, DNA double helix and starburst dendrimers. However, only the latter two surfaces are considered in detail in this report.", "doi": "10.1007/978-94-011-3396-8_8", "isbn": "9789401055024", "publisher": "Springer Netherlands", "place_of_publication": "Dordrecht", "publication_date": "1991", "pages": "121-139" }, { "id": "authors:2xaw2-n7643", "collection": "authors", "collection_id": "2xaw2-n7643", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20160520-131936011", "type": "book_section", "title": "What is biotechnology?", "book_title": "Biotechnology and Materials Science: Chemistry for the Future", "author": [ { "family_name": "Barton", "given_name": "Jacqueline K.", "orcid": "0000-0001-9883-1600", "clpid": "Barton-J-K" } ], "contributor": [ { "family_name": "Good", "given_name": "Mary L.", "clpid": "Good-M-L" } ], "abstract": "I have been given the task and opportunity of introducing chapters that describe some of the exciting new chemical advances in the field we call \"biotechnology\". You may notice that neither the words \"chemical\" nor \"molecular\" is incorporated into \"biotechnology\", but really the heart of what I think is exciting about this are is indeed chemical.", "isbn": "9780841214736", "publisher": "American Chemical Society", "place_of_publication": "Washington, DC", "publication_date": "1988", "pages": "3-6" } ]