Andrzej Z. Rys

Metal-nucleic acid cages.

Metal-nucleic acid cages are a promising new class of materials. Like metallo-supramolecular cages, these systems can use their metals for redox, photochemical, magnetic and catalytic control over encapsulated cargo. However, using DNA provides the potential to program pore size, geometry, chemistry and addressability, and the ability to symmetrically and asymmetrically position transition metals within the three-dimensional framework. Here we report the quantitative construction of metal-DNA cages, with the site-specific incorporation of a range of metals within a three-dimensional DNA architecture. Oligonucleotide strands containing specific environments suitable for transition-metal coordination were first organized into two DNA triangles. These triangles were then assembled into a DNA prism with linking strands. Metal centres were subsequently incorporated into the prisms at the pre-programmed locations. This unprecedented ability to position transition metals within a three-dimensional framework could lead to metal-DNA hosts with applications for the encapsulation, sensing, modification and release of biomolecules and nanomaterials.

Templated Ligand Environments for the Selective Incorporation of Different Metals into DNA

DNA has emerged as a unique template for the construction and organization of nanostructures and arrays with precisely controlled features. The incorporation of transition metals into DNA has enabled the transfer of functionality, in the form of enhanced stability, redox activity, photoactivity, and magnetic and catalytic properties, to this otherwise passive biomolecular template. A particularly attractive goal would be the selective incorporation of different transition metals into DNA. This allows the use of the programmable character of DNA to organize transition metals into arbitrarily designed symmetric or asymmetric structures, resulting in a number of applications in artificial photosynthesis, multimetallic catalysis, nanooptics, nanoelectronics, and data storage. It would also result in the expansion of the DNA “alphabet” to new metal “letters” that would increase the information content of this biomolecule and reduce errors in its assembly into nanostructures. For this goal to reached, different DNA–ligand environments must be designed in a manner that maximizes metalbinding selectivity, promotes close interaction between the metal complex and the DNA duplex, and offers coordination programmability. The incorporation of metals into DNA constructs has been demonstrated through replacement of the hydrogen-bonded DNA base pairs with metal complexes within the interior of the DNA duplex. 3] The extension of this strategy to different ligand environments is, however, limited by the steric and spatial requirements of the DNA duplex, and has been successful for planar metal centers that fit in the DNA interior. Metal complexes have been appended as nucleobase and (deoxy)ribose modifications; however, this method is generally limited to a small subset of kinetically inert and unreactive metal complexes that resist the harsh conditions of automated DNA synthesis. A third approach developed by our research group is to insert ligands into the phosphodiester backbone, such that the hybridization of DNA with its complementary strand templates the assembly of a metal-coordination environment in close contact with the DNA base stack. We report herein the site-specific incorporation of terpyridine (tpy) and diphenylphenanthroline (dpp) ligands into DNA strands. The DNAtemplated creation of three ligand environments resulted: tpy2:DNA, tpy:dpp:DNA, and dpp2:DNA. These ligand environments are highly selective for six-, five-, and fourcoordinate metal ions, respectively (Figure 1a). Thermal denaturation, UV/Vis and circular dichroism spectroscopy, and gel electrophoresis revealed a strong preference of the octahedral metal ions Fe and Co for the tpy2:DNA environment, with the highest reported thermal denaturation increase of any DNA structure upon Fe coordination. The dpp2:DNA environment is highly selective for the tetrahedral Cu ion, whereas tpy:dpp:DNA exhibits preference for the five-coordinate Cu ion. Moreover, “error correction” was observed if a metal ion was placed in the incorrect environment. Thus, Cu spontaneously oxidized to Cu if added to tpy:dpp:DNA, and Cu underwent spontaneous reduction to Cu if placed in dpp2:DNA. The four-coordinate Ag I ion was displaced by Cu when placed in the tpy:dpp:DNA structure. Finally, the addition of Fe to the tpy:dpp:DNA structure resulted in reorganization of the ligand environment, such that two of these constructs were brought together with Fe binding to their terpyridine units. In a similar manner to the ligand pockets of metalloenzymes, this new class of DNAtemplated coordination environments defines a toolbox for the selective positioning of different transition metals at exact locations within DNA nanostructures. Details of the synthesis, characterization, and solid-phase incorporation of the phosphoramidite derivatives of the dpp and tpy ligands into the DNA (Figure 1c) can be found in the Supporting information. The tpy and dpp derivatives were both designed to have flexible diethylene glycol spacers that would enable placement of their aromatic moieties in close proximity to the DNA base stack to promote strong interaction and chirality transfer from the B-DNA duplex upon metal binding (Figure 1b). The selective insertion of tpy and dpp at the 5’ and 3’ termini of complementary DNA strands a and b, followed by hybridization, resulted in the formation of three DNA-templated coordination spheres: tpy2:ab, tpy:dpp:ab, and dpp2:ab (Figure 1a). In contrast to metal-driven supramolecular coordination, 10] the programmed self-assembly of duplex DNA can template the formation of any combination of ligands, whether homoleptic or mixed, in close proximity. We studied the thermal stability of DNA duplexes tpy2:ab and their metal complexes (Figure 2a). For these duplexes, even without the addition of a metal, the melting temperature increased from 43 8C for the unmodified DNA to 66 8C for tpy2:ab. This increase is possibly a result of p stacking of the tpy ligands on the DNA base stack, or interactions of tpy ligands with Na or H ions in the buffer solution. [*] H. Yang, A. Z. Rys, C. K. McLaughlin, Prof. H. F. Sleiman Department of Chemistry, McGill University 801 Sherbrooke Street West, Montreal, Quebec H3A 2K6 (Canada) Fax: (+ 1)514-398-3937 E-mail: hanadi.sleiman@mcgill.ca

Recent chemistry of the chalcogen diatomics

Abstract The chemistry of the generation and trapping of diatomic sulfur (S 2 ) and sulfur monoxide (SO) are reviewed with special emphasis on recent work, including initial efforts to detect and trap diatomic selenium (Se 2 ).

Insertion of a two sulfur unit into the S–S bond—tailor-made polysulfides

Abstract Triphenylthiosulfenyl chloride (1) reacts with disulfides RSSR, yielding tetrasulfides as the main products. The results of the insertion for different R groups are reported. A two-step mechanism involving the formation of unsymmetrical trisulfide intermediates containing the trityl group is proposed.

Sulfuration of dienes with elemental sulfur

Abstract Elemental sulfur reacts with conjugated 1,3-dienes to deliver cyclic di- and polysulfides; the reaction proceeds without any activation other than heat. Treatment of cyclic polysulfide products with triphenylphosphine cleanly converts them to the corresponding disulfide in good overall yield. Additionally, some mechanistic aspects have been examined. The presence of disulfur as an active species in the sulfuration of dienes with S 8 is discussed.

A novel synthesis of organic diselenapolysulfides

Abstract A family of organic polychalcogenides with a common structure of RSeSxSeR (with x=1, 2, 3 and R=CH3, Ph, PhCH2, O2NC6H4CH2) as well as cyclic 5,5-dimethyl-1,2-dithia-3,7-diselenacycloheptane were synthesized in good yield and high purity from the reaction of Ph3CSxCl with corresponding diselenides in chloroform at room temperature. Mechanistic aspects of the insertion involving the formation of an intermediate (RSeSxCPh3) are discussed.

CATALYTIC SULFURATION OF DIENES WITH METALLOCENE POLYSULFIDES

Abstract Elemental sulfur reacts with conjugated 1,3-dienes to give cyclic di-and tetrasulfides. The yield is significantly improved in the presence of catalytic amounts of organometallic polysulfides. The nature of this effect is discussed.

Preparation and reactivity of unsymmetrical di- and trisulfides

Triphenylmethanesulfenyl chloride TrSCl (6) and triphenylmethanethiosulfenyl chloride TrSSCl (7) react with various thiols RSH to give the corresponding unsymmetrical polysulfides TrSSR 9 and TrSSSR 10, respectively. Compounds 9 and 10 were obtained in excellent yield and identified by 1H- and 13C-NMR as well as by elemental analysis. p-Methoxybenzyl trityl trisulfide 10c was characterized by X-ray crystallography. Preliminary experiments showed an interesting reactivity of trisulfides TrSSSR 10 with electrophiles to give polysulfides RSXR; the use of elemental iodine results in the formation of the corresponding hexasulfides RS6R, 15 in high yield and with higher than 90% selectivity.

A novel method for the preparation of unsymmetrical bis (di- and trisulfides) via trityl sulfenyl chlorides: Precursors for cyclic polysulfides

When triphenylmethanesulfenyl chloride 6 [(C6H5)3CSCl] and its thio homologue 7 [(C6H5)3CSSCl] were treated with dithiols, unsymmetrical bis(di- and trisulfides) 11 and 12 were produced in high yields. Final products were determined by 1H and 13C NMR as well as by elemental analysis. The X-ray crystallographic structures of p-di(methylenedithiotrityl)benzene 11a and p-di(methylenetrithiotrityl)benzene 12a were obtained. In addition, cyclic polysulfide 13 was produced in high isolated yield via 11c.

Structure of ditrityl-2-selenatrisulfide

The X-ray crystal structure determination of ditritylseleno trisulfide 5 was obtained. C 38 H 30 S 2 Se, Mr=629.74, monoclinic, p 2 1 / n , a =14.078(4), b =12.852(4), c =17.171(6) Å, β=98.08(2)°. V =3070.7 Å 3 , Z =4, Do=1.37 g/cm 3 , MoK α , λ=0.71069 Å, μ=14.66 cm −1 , F (000)=370, T =293(2) K, R ( R w )=0.0355(0.0342) for 2895 observed independent reflections [ F >2.5σ( F )], goodness of fit=1.104. The material was obtained by reacting trityl thiol 6 with the first selenium transfer reagent bis- N -benzotriazol-1-yl selenide 7 .