Found 24 Abstracts CONTROL ID: 1688327TITLE: Synthesis, DNA interactions and Cytotoxicity of mixed ligand Cu (II) complexes.AUTHORS/INSTITUTIONS: R. Singh, D. Chakraborty, chemistry, The Maharaja Sayajirao University of baroda,Vadodara, INDIA|CURRENT CATEGORY: Metals and Nucleic AcidsABSTRACT BODY: Abstract Body: The clinical success of cisplatin, and platinum based drugs,as anti-cancer agents constitutes the mostimportant contribution to the use of metals in medicine.The major concerns associated with these anti-cancermetallodrugs, include problems with resistance, toxicity and other side effects.The main cellular target for platinumdrugs is genomic DNA and the major antitumor activity results from inhibition of DNA replication.Hence,considerableefforts are still ongoing to find more effective DNA targeting drugs with fewer side effects. Evaluation of the ‘chemical nucleases’,which can cleave DNA by several pathways,namely nucleobase oxidation,phosphate ester hydrolysis and deoxyribose sugar oxidation could be another approach to design new antineoplasticmetallodrugs targeting cellular DNA.The most efficient chemical nucleases contain transition metal ions, like redox-active Cu, Fe, or the redox-inactive Zn in their active sites.Cu(II) has a long history of medical use, and its prospectiveantitumor properties have attracted attention recently because it is thought to be less toxic than nonessential metals,such as Pt.The mechanism involved in the cleavage of DNA is probably initiated by the intercalation of the highlyplanar Cu(II) complex.The use of structurally different ligands is expected to provide a better understanding of thefactors that are crucial for the DNA cleavage activity of these type of complexes, allowing a more rational approach forthe development of Cu(II) complexes with potential anti-cancer properties. These studies inspired us to synthesizemixed ligand Cu(II) complexes of the fluoroquinolone drug moxifloxacin and ferrocene conjugated amino acids andinvestigate their DNA binding & nuclease activities.Apoptosis (programmed cell death) is desirable in chemotherapy and therefore induction of apoptosis is one of theconsiderations in development of anticancer drugs.The realization that apoptosis is a key factor that contributes toantitumor activity of chemotherapeutic drugs, has led us to evaluate the cytotoxic behaviour of the synthesizedcomplexes and their mechanism of action.

CONTROL ID: 1706374TITLE: A Message Regarding Nucleic Acids.A Suitable Primary Binding Site Facilitates Metal Ion Coordination to a Hydroxyl Group!AUTHORS/INSTITUTIONS: H. Sigel, A. Sigel, Department of Chemistry/Inorganic Chemistry, University of Basel,Basel, SWITZERLAND|CURRENT CATEGORY: Metals and Nucleic AcidsABSTRACT BODY: Abstract Body: Knowledge on the binding of biologically relevant divalent metal ions (M(II)) to hydroxyl groups isscarce despite its importance, e.g., for ribozymes [1]. For an overview on the existing literature we joined forces withseveral colleagues [2] and it turned out that a suitable primary binding site (PBS) in a favorable steric orientation iscrucial for a M(II)-hydroxyl group interaction. We studied the position of the intramolecular isomeric equilibriumbetween an open form, in which M(II) is solely coordinated to PBS, and a closed or chelated form, in which M(II) isalso bound to the hydroxyl group. We concentrated on the alkaline earth ions as well as on Mn(II), Co(II), Ni(II), Cu(II),and Zn(II). The following PBSs were considered: Phosph(on)ate, carboxylate, amino, imidazole or pyridyl groups. For5-membered chelates the extent of chelate formation increases in the given order of the PBSs. The formation degreesof the chelates vary widely, i.e., from a few to nearly 100%. For complexes formed with hydroxyacetate (= glycolate =HO–CH2–COO– = HOAc–), one obtains for Mg(HOAc)+ and Zn(HOAc)+ formation degrees of the chelates of 71±5%and 91±1%, respectively. Interestingly, the formation degree of the closed Ca(HOAc)+ isomer is with 83±3% largerthan the one of Mg(HOAc)+. Maybe here is the reason for the atypical strong influence of Ca(II) on group II intronribozyme catalysis and folding [3]. The relevance of the indicated results for biological systems is obvious, especiallybecause a reduced solvent polarity favors M(II)-hydroxyl group interactions [2]. Naturally, the M(II)-hydroxyl bindinggives rise to enhanced complex stabilities, log delta, from which the formation degrees can be calculated [4]. Supported by the Department of Chemistry, University of Basel. [1]R.K.O. Sigel, A.M. Pyle, Chem. Rev. 107 (2007) 97-113.[2]F.M. Al-Sogair, B.P. Operschall, A. Sigel, H. Sigel, J. Schnabl, R.K.O. Sigel, Chem. Rev. 111 (2011) 4964-5003.[3]M. Steiner, D. Rueda, R.K.O. Sigel, Angew. Chem. Int. Ed. 48 (2009) 9739-9742.[4]H. Sigel, L.E. Kapinos, Coord. Chem. Rev. 200-202 (2000) 563-594.(No Image Selected)

CONTROL ID: 1707767TITLE: Binding Interactions between Nickel Schiff Base Complexes and Quadruplex DNAAUTHORS/INSTITUTIONS: K.J. Davis, C. Richardson, J.L. Beck, S.F. Ralph, School of Chemistry, University ofWollongong, Wollongong, New South Wales, AUSTRALIA|CURRENT CATEGORY: Metals and Nucleic AcidsABSTRACT BODY: Abstract Body: Quadruplex DNA (qDNA) is a less common nucleic acid secondary structure present in non-codingregions at the ends of chromosomes known as telomeres. Since many base pairs are lost from the ends of DNAstrands during replication, telomeres function to protect chromosomes during this process. However, when DNAbecomes so short that it can no longer function as the template for protein synthesis, the cell enters apoptosis, orprogrammed cell death. In contrast, approximately 85% of tumour cells possess elevated levels of the enzymetelomerase, which is responsible for maintaining the length of telomeres and contributes to tumour cell immortality.The normal substrate for telomerase is the single stranded overhang regions present at the end of telomeres. Theseregions are rich in guanines, and consequently prone to forming qDNA structures. Drugs that can bind selectively toexisting qDNA structures or induce formation of such structures may be able to inhibit telomerase and act as novelanti-cancer agents. One group of compounds that has shown promise in this area are substituted Schiff basecomplexes of various metals. The work presented here further explores the potential of nickel(II) Schiff basecomplexes as selective qDNA binders, and inhibitors of telomerase, by varying the number and position of aromaticring systems in the Schiff base structure, as well as the identity of side chains designed to interact with the qDNAgrooves. One complex of interest is (1), which includes the meso-1,2-diphenylethylenediamine unit as part of itsstructure. This complex binds poorly to duplex DNA, but is able to bind to a tetramolecular qDNA structure, indicatingthat it is possible to engender selectivity for qDNA structures through the usage of the above non-planar moiety. Weare currently using a variety of methods, including electrospray ionisation mass spectrometry (ESI-MS) and CDspectroscopy, to explore the interactions between different types of qDNA and the nickel complexes.

Figure 1. (a) ESI mass spectrum of a solution containing a 3:1 ratio of (1) and a tetramolecular qDNAmolecule. (b) ESI mass spectrum of a solution containing a 3:1 ratio of (1) and a duplex 16mer DNAmolecule.

CONTROL ID: 1707958TITLE: Metal-dependent Stabilization of Artificial DNA Junction StructuresAUTHORS/INSTITUTIONS: Y. Takezawa, J. Duprey, S. Yoneda, M. Shionoya, Department of Chemistry, GraduateSchool of Science, The University of Tokyo, Tokyo, JAPAN|CURRENT CATEGORY: Metals and Nucleic AcidsABSTRACT BODY: Abstract Body: DNA molecules have been expected to serve as promising components for nanoscale moleculararchitectures due to their well-ordered structure and highly programmable nature. We have developed metal-mediatedbase pairs as additional functional building blocks of DNA structures, in which natural hydrogen bonds betweennucleobases were replaced by metal coordination bonds, and have demonstrated significant stabilization of theduplexes. In this study, we synthesized a novel metal-conjugated DNA structure involving a three-way junction, whichis one of the key components of 2D and 3D DNA nanoarchitectures.
We designed a DNA three-way junction structure with a preorganized metal binding site at its core. Bidentatebipyridine (bpy) ligands were attached to the nucleosides positioned at the center of each strand via Cu-catalyzedHuisgen cycloaddition (Ubpy). The melting profiles of the resulting three-way junction were investigated in thepresence of various transition metal ions. The results showed that the addition of equimolar amounts of Ni2+ ionremarkably stabilized the junction structure by 12 °C compared to the unmodified junction. In contrast, three-wayjunctions with only one or two bpy ligands showed little stabilization upon Ni2+ addition. Thus, the stabilization wasattributed to metal-mediated crosslinking among three DNA strands through the formation of a Ni(bpy)3

2+ complex atthe junction point as further evidenced by the UV spectral changes. Furthermore, CD spectroscopy indicated thepredominant formation of the Λ-isomer that could be a result of the chiral DNA environment at the core of the three-way junction.
The “metal-locked” DNA junction motif presented here will have future applications in the field of DNAnanoarchitectures as a building block for stabilization and conformation switching of whole DNA structures byreversible metal complexation.
[1] Y. Takezawa, M. Shionoya, Acc. Chem. Res. 2012, 45, 2066. [2] J.-L. H. A. Duprey, Y. Takezawa, M. Shionoya,Angew. Chem., Int. Ed. 2013, 52, 1212.

CONTROL ID: 1712972TITLE: DNA recognition by lanthanide-peptide complexesAUTHORS/INSTITUTIONS: L. Ancel, C. Gateau, C. Lebrun, P. Delangle, CEA SCIB, Grenoble, Isère, FRANCE|CURRENT CATEGORY: Metals and Nucleic AcidsABSTRACT BODY: Abstract Body: Lanthanide ions are powerful luminescent tools thanks to their unique spectroscopic properties (longlived exited state, narrow band emission). Because of the similarity of their ionic radii with Ca 2+[1], studies were doneon the design of peptides scaffold able to coordinate Ln3+[2] ions We demonstrated that hexapeptides containing twounnatural amino acids bearing aminopolyacetate side chains (tridentate or pentadentate) and a tryptophan residue asTb3+sensitizer provide lanthanide-peptide complexes sufficiently stable to avoid dissociation in water at physiologicalpH. [3,4] Compounds that bind DNA, an essential biomolecule that is storing and dispensing genetic data required for life, areextremely useful as biochemical tools for visualization of DNA both in vitro and inside the cell. That’s why, wecombined our lanthanide peptide complexes with DNA recognition units for the detection of DNA double helix. We present here hexapeptide sequences containing DNA intercalating units. The intercalators were inserted in thepeptide sequences in place of tryptophan and are expected to sensitize the Eu3+ cation luminescence. Taking advantage of Ln3+luminescence properties, we demonstrated that the intercalating unit are able to sensitizeEu3+and that a unique EuP complex is formed in water at physiological pH. Luminescence, DNA melting temperatureand absorbance measurements demonstrate that the EuP complexes bind ct-DNA through an intercalative process asefficient as the free intercalator core. Hence, the time resolved luminescence of europium in these novel complexesefficiently senses the interaction with DNA.[5] Acknowledgements: Financial support Rhône-Alpes Region and CEA Grenoble 1 E.Pidccock, G.R.Morre, J. Biol. Inorg. Chem, 2001, 6, 4792 M.Nitz, K.JFrantz, R.L.Maglathlin, B.Imperiali, ChemBioChem, 2003, 4, 2723 F.Cisnetti, C.Gateau, C.Lebrun, P. Delangle, Chem. Eur. J., 2009, 15, 74564/ A.Niedzwiecka, F.Cisnetti, C.Lebrun, P.Delangle, Inorg Chem, 2012, 51, 54585/ L.Ancel, C.Gateau, C.Lebrun, P.Delangle, Inorg. Chem.,2013 , 52, 552

CONTROL ID: 1714042TITLE: Structural insights into complex between human telomeric quadruplex DNA and N-methylmesoporphyrin IXAUTHORS/INSTITUTIONS: L.A. Yatsunyk, S.T. Miller, J.M. Nicoludis, S.P. Barrett, Chemistry and Biochemistry,Swarthmore college, Swarthmore, Pennsylvania, UNITED STATES|CURRENT CATEGORY: Metals and Nucleic AcidsABSTRACT BODY: Abstract Body: N-methyl mesoporphyrin IX (NMM) is an excellent G-quadruplexes (GQ) ligand with a wide range ofapplications in biology and chemistry. Here, we present the X-ray crystal structure of a complex between NMM andhuman telomeric DNA dAGGG(TTAGGG)3, Tel22, determined in two space groups, P21212 and P6, at 1.65 and 2.15Å resolution, respectively. The former is the highest resolution structure of the human telomeric GQ DNA reported todate. The biological unit contains a Tel22 dimer of 5'-5' stacked parallel-stranded quadruplexes capped on both endswith NMM, supporting the spectroscopically determined 1:1 stoichiometry. NMM is capable of adjusting itsmacrocycle geometry to closely match that of the terminal G-tetrad required for efficient π-π stacking. The out-of-plane N-methyl group of NMM fits perfectly into the center of the parallel GQ core where it aligns with potassium ions.In contrast, the interaction of the N-methyl group with duplex DNA or antiparallel GQ would lead to steric clashes thatprevent NMM from binding to these structures, thus explaining its unique selectivity. Based on the biochemical data,binding of NMM to Tel22 does not rely on relatively non-specific electrostatic interactions, which characterize mostcanonical GQ ligands. NMM could serve as an important prototype for the development of truly selective GQ ligands,and our structural data will help inform the further developments in this area.

Figure 1. Biological unit of Tel22-NMM structure. Quadruplex dimer is formed by head-to-head stacking of 5’ G-tetrads from two monomers. This dimer is capped by two NMM molecules; the binding mode is known as end-stacking. This is the first crystallographic observation of porphyrin stacking onto a guanine quadruplex. Note, our andothers earlier spectroscopic studies suggested this biding mode.

CONTROL ID: 1714549TITLE: Investigating the Interactions of Metal Complexes with G-Quadruplex forming DNAAUTHORS/INSTITUTIONS: H. Pritchard, M.J. Hannon, School of Chemistry, University of Birmingham, Edgbaston,UNITED KINGDOM|CURRENT CATEGORY: Metals and Nucleic AcidsABSTRACT BODY: Abstract Body: Many metal complexes used as anticancer drugs that target DNA are aimed at duplex DNA, forexample Cisplatin. DNA is in its duplex form when in ‘sleep mode’ therefore it may be more useful to target structuresseen in DNA when processes like replication, protein synthesis and transcription are occurring.

Of particular interest are the G-quadruplexes found in the promoter regions of the c-myc proto-oncogene. Theactivated promoter region of c-myc has been linked to the production of growth stimulating genes in many types ofcancer. When G-quadruplexes are able to form in this region they can prevent the action of certain proteins whichrequire single stranded DNA binding in order to turn on the activity of the cell. Therefore the work presented here isbased on the design of a complex that has the potential to be an efficient G-Quadruplex binder. The basic concept of the complex design was to use a ligand structure that is planar with the ability to π stack onto thetop face of a G-quadruplex. Preference for G-quadruplex binding over duplex binding should arise if the ligand islarge enough; hence a biisoquinoline unit was chosen. Incorporating a metal into the structure provides favourableelectrostatic interactions with the DNA which in this case was achieved by using palladium and platinum respectively.Circular Dichroism results of the palladium complex in the presence of 100 mM KCl show an induced signal at 380 nmwhen titrating against telomeric DNA. A possible change in conformation of the quadruplex from antiparallel to parallelis also observed. Similar results can also be seen with cmyc DNA. Fluorescent indicator displacement experimentsshow very promising DC50 values below 0.5 µM for the Htelo DNA (telomeric sequence) and cmyc DNA which arecomparable to those quoted in the literature for good G-quadruplex binders.

Structure of biisoquinoline complex (alongside a G-quartet) and the palladium complex CD spectrum with Htelo DNA(ratio 0-8:1) in the presence of 100 mM KCl, 10 mM Tris-HCl

CONTROL ID: 1714935TITLE: Palladium(II) complexes with N,S-donor ligand: Synthesis, cytotoxicity, DNA interaction and topoisomerase IIinhibition AUTHORS/INSTITUTIONS: F. Rocha, C. Barra, A. Mauro, A. Godoy Netto, Química Geral e Inorgânica, UniversidadeEstadual Paulista - Júlio de Mesquita Fillho, Araraquara, SP, BRAZIL|I. Carlos, Departamento de Análises Clínicas,Universidade Estadual Paulista - Júlio de Mesquita Fillho, Araraquara, SP, BRAZIL|S. Garrido, Bioquímica etecnologia, Universidade Estadual Paulista - Júlio de Mesquita Fillho, Araraquara, SP, BRAZIL|L. Nauton, M. ElGhozzi, A. Gautier, CNRS UMR 6296, Clermont–Université, Université Blaise Pascal, Clermont-Ferrand, FRANCE|L.Morel, GreD UMR 6247 CNRS, INSERM U931, Clermont–Université, Université Blaise Pascal, Clermont-Ferrand,FRANCE|CURRENT CATEGORY: Metals and Nucleic AcidsABSTRACT BODY: Abstract Body: Pd(II) complexes are interesting alternative candidates for metal antitumor drugs due to their structuralsimilarities to Pt(II) complexes. A good strategy to afford new biologically active compounds is incorporateN,S–chelating ligands in square-planar complexes. Motivated by the potential uses of these compounds as anticanceragents, we present the synthesis and cytotoxicity of four cationic complexes of the type [PdX(PhT)(PPh3)]X {X = Cl (1); Br (2); I (3); SCN (4); PhT = 4–phenyl–3–thiosemicarbazide} and their ability to interact with DNA andtopoisomerase II.The synthesis of 1-4 was achieved starting from bisacetonitriledichloropalladium(II). First, triphenylphosphine (PPh3)and PhT displace the labile ligands acetonitrile and one of the two Cl atoms to obtain 1. In a second step, the Cl atomsare easily replaced by Br, I and SCN ions by the addition of two equivalents of their appropriate potassium salt toafford 2–4.The formation of the N,S-chelated products was proved by spectroscopic data. IR spectra show an important variationof 30 cm-1 for the νC=S after complexation. Variation of ~ 4 ppm downfield of the chemical shift (1H NMR) wasobserved for the two N2 protons after complexation. Ultimately, the structure was proved by X–ray diffraction of acrystal of complex 3 (figure 1).The cytotoxicity of the complexes and cisplatin were determined against two murine cell lines, LM3 (mammaryadenocarcinoma) and LP07 (lung adenocarcinoma). Compounds 1–4 exhibited good activity that overcame cisplatin’sin the case of LM3. The binding of the complexes with a purine base (guanosine) was investigated by 1H NMR andmass spectrometry, showing that the coordination of guanosine occurred through N7. However, gel electrophoresisassay demonstrated that 1–4 unwind the DNA plasmid only at high concentrations, suggesting that the cytotoxicitymechanisms of 1-4 may not necessarily involve interaction with DNA. Therefore, the ability of complexes to act astopoisomerase II inhibitors was tested and the results showed that the compounds 2-4 inhibited this enzyme atconcentrations between 5 – 25 µM.

Figure 1. ORTEP view of complex 3.

CONTROL ID: 1714936TITLE: DNA binding and citotoxicity of Pd(II) complexes bearing 1,10-phenanthroline and thioureas ligandsAUTHORS/INSTITUTIONS: C.V. Barra, F.V. Rocha, A.E. Mauro, R.C. Frem, A.V. Godoy Netto, Departamento deQuímica Geral e Inorgânica, IQ - Unesp - Araraquara, Araraquara, BRAZIL|L. Morel, GreD UMR 6247 CNRS,INSERM U931, Clermont–Université, Université Blaise Pascal, Clermont-Ferrand, FRANCE|A. Gautier, CNRS, UMR6296, Clermont–Université, Université Blaise Pascal, Clermont-Ferrand, FRANCE|CURRENT CATEGORY: Metals and Nucleic AcidsABSTRACT BODY: Abstract Body: Metallointercalators represent a promising alternative in cancer chemotherapy. Modifications at theintercalator backbone as well the ancillary ligand may result in changes in the binding modes, drug DNA associationconstants and cytotoxicity. We present herein DNA binding and cytotoxic studies on a series of complexes of generalformulae [Pd(phen)L2]

2+ incorporating the intercalator 1,10-phenanthroline and thiourea ligands (L = thiourea 1, N-methylthiourea 2, N,N’-dimethylthiourea 3).The binding constants (Kb) for the interaction of the complexes with SS-DNA were determined by UV spectroscopy.The values obtained for Kb were 4.8×10

4 M−1 – 7.0×104 M−1, which falls in the range of what found formetallointercalators. Competitive experiments with ethidium bromide (EB) were investigated by fluorescencespectroscopy and show that all the complexes were able to displace EB from the DNA–EB complex, which is alsoindicative of an intercalative mode of binding. DNA-unwinding results showed that the complexes can induce theunwinding of the plasmid DNA. In order to verify the ability of the complexes to interact covalently with DNA,guanosine was used as a model system and the reaction was monitored by 1H NMR. As expected, the reaction hasnot occurred, excluding the possibility of covalent interaction.Compounds were tested against KB (oral carcinoma), MCF7 (human breast carcinoma) and MCF7-R (resistanthuman breast carcinoma) cell lines. Cytotoxic effects were expressed as cellular viability (Figure). Although thecomplexes were inactive towards MCF7 cells at 10 µM, they showed good cytotoxic activity towards MCF7-R. Thisfinding suggest that the cytotoxicity mechanisms of the Pd(II) compounds differ from that observed for cisplatin.Complexes 2 and 3 were more active than 1 in both KB and MCF7-R cells. From DNA binding experiments, thereappears to be no significant difference between any of the metal complexes, suggesting that DNA binding affinity isnot a key determinant of the observed difference in their cytotoxicity.

Effect of the complexes on tumor cells viability after 48 h of incubation

CONTROL ID: 1715517TITLE: Introducing Selectivity to Differential Protein SensorsAUTHORS/INSTITUTIONS: L. Motiei, D. Margulies, Weizmann Institute of Science, Rehovot, ISRAEL|CURRENT CATEGORY: Metals and Nucleic AcidsABSTRACT BODY: Abstract Body: Current approaches to disease diagnosis and proteomics are largely based on the ability ofmonoclonal antibodies to bind protein biomarkers with high affinity and selectivity. In recent years, however, analternative approach has been developed in which combinations of proteins are identified using cross-reactive sensorarrays that are inspired by the olfactory neural system. Although such devices have been shown to detect proteinsquickly and effectively, all of them suffer from a major limitation, namely, their inability to identify proteins withinmixtures.We have designed, synthesized, and prepared pattern-based detection arrays that can discriminate betweenGlutathione S-Transferases (GSTs) in biological mixtures. GSTs were chosen as the protein targets because differentexpression profiles within this family have been associated with the progression of various diseases. Our fluorescentarrays are based on modified DNA-duplexes that can bind these enzymes with dual interaction modes: specific andnon-specific. On one hand, they bind the enzymes' active site with high affinity and selectivity. On the other hand, theypossess a nonspecific binding region that enables them to differentiate between closely related isozymes. Our resultsindicate that these arrays can discriminate between different combinations and concentrations of GSTs even in thepresence common serum proteins such as immunoglobulin G and transferrin.

CONTROL ID: 1715576TITLE: Dinuclear Ruthenium-Silicon Complexes as DNA and G4 DNA Binding AgentsAUTHORS/INSTITUTIONS: J. Henker, S. Glöckner, E. Meggers, FB Chemie, Philipps-Universität Marburg, Marburg,GERMANY|CURRENT CATEGORY: Metals and Nucleic AcidsABSTRACT BODY: Abstract Body: Octahedral metal complexes permit the construction of demanding globular and rigid structures due totheir sophisticated stereochemistry and chelation-induced conformational restrictions. Utilizing these features led tothe design of kinetically inert metal-based enzyme inhibitors and nucleic acid binders with interesting properties likeDNA-light-switch behavior.[1,2] However, general concerns about the toxicity of such complexes prevent their wideuse in biomedical research and therapy.[3] Thus finding less harmful substitutions for the metal center is an upcomingchallenge. An excellent replacement is silicon, because of lower toxicity and its availability in larger amounts. Even though siliconis the higher homologue of carbon, silicon does not show the same structural limitations as a coordination numberbeyond four is possible. As a consequence, silicon is able to build up penta- and hexacoordinated complexes that areinteresting and structurally stable substitutions for a missing hypervalent carbon. In our group, the use of silicon as acoordination center is well investigated and we are able to synthesize octahedral silicon complexes with threebidentate ligands.[3] These complexes are hydrolytically completely stable and can easily be modified by standardorganic reactions like nitration or halogenation. Furthermore, we expect that multinuclear silicon complexes provide interesting chemical and physicochemicalproperties that can be used in different biological applications, for example DNA binding or protein surface recognition.As a starting point for the synthesis of such complexes, we first synthesized different dinuclear complexes composedof a ruthenium and a silicon center bridged by a dppzOH-ligand. These complexes show a strong affinity to DNA, witha binding constant to duplex DNA and G4 DNA of about 106–107 M-1 and thus within the range of the known, strongDNA binding agents [Ru(dppz)(phen)2]

2+ and [Ru(bpy)2(μ-dppz)Ru(bpy)2]4+.[2,3]

[1] Blanck et al., Organometallics 2011, 30, 4598-4606.[2] Lutterman et al., J. Am. Chem. Soc. 2008, 130, 1163-1170.[3] Xiang et al., Chem. Commun. 2012, 48, 7131-7133.

CONTROL ID: 1716075TITLE: Study of Mn(II)-DNA interaction using pulsed high magnetic-field Electron Paramagnetic Resonance.AUTHORS/INSTITUTIONS: E.M. Bruch, L.C. Tabares, S. Un, DSV, CEA-Saclay, Gif-sur-Yvette, Île-de-France,FRANCE|CURRENT CATEGORY: Metals and Nucleic AcidsABSTRACT BODY: Abstract Body: The interaction of DNA with Mn(II) was studied using pulsed high magnetic-field ElectronParamagnetic Resonance techniques (ENDOR and PELDOR-NMR). Several nucleic acids (genomic DNA anddimeric or monomeric oligonucleotides) and free nucleotides were used as models for the interaction. ENDOR wasused to study the amount and the nature of 31P from the backbone bound to the manganese and PELDOR-NMR wasused to detect the binding to the nitrogen of the bases. The details of the interaction of this metal with nucleic acids, studied mainly by crystallographic techniques, havesuggested that the metal interacts with the N7 of a guanosine or via a coordinated water molecule with the phosphatebackbone. Also Mn-nucleic acids complexes show a broad 31P ENDOR spectrum with a high splitting. This signal hasonly been observed in Mn-nucleic acids complexes and has been attributed to a metal bound to a phosphate and theN7 of a guanosine simultaneously.Our results indicate that the metal can interacts directly with both the phosphate backbone via the oxygen and thebases via the nitrogen depending on the relative Mn(II)/nucleic acids ratio. Also we found that the 31P ENDORspectrum characteristic from nucleic acids doesn’t require the metal binding the base and the backbonesimultaneously. On the other hand the interaction with the backbone appears to be direct and independent of thedimerization state of the oligonucleotide. Finally, for the oligonucleotides used in this work, the nature of the interactionappears to be independent of the nucleotide composition.(No Image Selected)

CONTROL ID: 1716084TITLE: Use of Osmium (III) Complexes to determine influence of base mismatches on DNA-Protein CrosslinkingAUTHORS/INSTITUTIONS: K.R. Miller, Z.A. Perez, E.D. Stemp, Physical Sciences and Mathematics, Mount St.Mary's College, Los Angeles, California, UNITED STATES|K.N. Schaefer, Chemistry and Chemical Engineering,California Institute of Technology, Pasadena, California, UNITED STATES|CURRENT CATEGORY: Metals and Nucleic AcidsABSTRACT BODY: Abstract Body: 8-oxoguanine is a common oxidation product in DNA and can lead to missense mutations. Themetallointercalator Ru(phen)2dppz2+ is a useful luminescent probe for DNA that has also found use as a guanine-selective oxidizing agent via the flash-quench technique. Here, we introduce its osmium analogue as a way toselectively oxidize 8-oxoguanine in double-stranded DNA as visualized by DNA-protein crosslinking and Maxam-Gilbert sequencing. With a 3+/2+ couple of 1.15 V, Os(phen)2dppz3+ , this metallointercalator should be able tooxidize 8-oxo-G (~0.7 V) without oxidizing guanine (~1.3V). MALDI mass spectrometry data confirms that oxidizingguanine using Ru(NH3)63+ and Ru(phen)2dppz2+ produces 8-oxoguanine. In plasmid DNA where 8-oxo-G has beenincorporated as above, further flash-quench treatment with Os(phen)2dppz2+ and Co(NH3)5Cl2+ leads to crosslinkingwith histone protein in gel shift experiments. Furthermore, in gel shift experiments with a duplex of the oligonucleotide5’-ATATGATAT8GATATGATAT -3’ (8 = 8-oxo-G), flash-quench treatment with Ru(phen)2dppz2+ in the presence ofhistone produces a band of intermediate mobility (presumably 1:1 crosslink) and well-shifted material. In contrast,analogous treatment with Os(phen)2dppz2+ produces only the band of intermediate mobility, consistent with thepresence of only a single site that is oxidizable by the osmium complex. A Maxam-Gilbert sequencing gel showsdamage only at the 8-oxo-G site upon flash quench treatment with the osmium complex, as expected. Lastly, controlexperiments indicate that with a duplex of the oligonucleotide 5’-ATATGATATGGATATGATAT -3’ flash quenchtreatment with Ru(phen)2dppz2+ in the presence of histone produces well-shifted material, whereas treatment withOs(phen)2dppz2+ does not produce crosslinked material, as expected since the osmium (III) complex formed shouldnot be capable of guanine oxidation. Taken together, these results show that Os(phen)2dppz2+ is a promisingselective oxidant of 8-oxoguanine in double stranded DNA.(No Image Selected)

CONTROL ID: 1716238TITLE: Setting up photoinduced charge transfer through metal-modified nucleic acids: Towards molecular wiresAUTHORS/INSTITUTIONS: B.S. Dave, S. Johannsen, R. Sigel, Institute of Inorganic Chemistry, University of Zürich,Zürich, SWITZERLAND|CURRENT CATEGORY: Metals and Nucleic AcidsABSTRACT BODY: Abstract Body: Nucleic acids are propitious candidates for the use as templates to design molecular wires andmagnets on nano-scale. This is mainly attributed to their superb self-assembly properties and robust structuralfeatures. Although the conductivity of natural nucleic acids is insufficient for their direct application in nano-scaleelectronic architectures, the site-specific functionalization of nucleic acids can overcome this shortcoming.[1] Theformation of metal-mediated base pairs is the most prominent method to insert metal ions in a specific manner alongthe helix of nucleic acid.[2–4]Our goal is to study the electronic properties of such metal-modified nucleic acids. Using metallointercalators as anelectron donor-acceptor couple we are setting-up a photoinduced charge transfer experiment with metal-modifiedRNA duplexes. Our RNA duplexes contain continuous stretches of 2, 3 and 6 uracil-uracil mismatches that form U-Hg(II)-U base pairs upon addition of Hg(II) ions.[4] As a first step towards setting-up our experiment, we characterizethe binding of the donor metallointercalator [Ru(bpy)2dppz]2+ using absorption and emission experiments. Our datasuggests an intercalative mode of binding between the metallointercalator and our Hg(II)-modified RNA duplexes.Intercalative binding is a feasible method through which an electron can be injected into the base-stack of nucleicacids without covalently attaching metal complexes to it. These studies are an important step to further developmentof the charge transfer experiment of metal-modified nucleic acids. Financial support by the Swiss National Science Foundation (to SJ and RKOS), the University of Zurich, within theCOST Action CM1105 is gratefully acknowledged. 1.S. Liu; G. H. Clever; Y. Takezawa; M. Kaneko; K. Tanaka; X. Guo; M. Shionoya, Angew. Chem. Int. Ed. 2011,50, 8886.2.K. Tanaka; M. Shionoya, J. Org. Chem. 1999, 64, 5002.3.S. Johannsen; N. Megger; D. Böhme; R. K. O. Sigel; J. Müller, Nat. Chem.2010, 2, 229.4.S. Johannsen; S. Paulus; N. Düpre; J. Müller; R. K. O. Sigel, J. Inorg. Biochem. 2008, 102, 1141. (No Image Selected)

CONTROL ID: 1716240TITLE: DNA labeling of vitamin D receptor gene by using schiff baseAUTHORS/INSTITUTIONS: E. Maltas, Department of Chemistry, Selcuk University,Faculty of Science, Konya,TURKEY|M. Findik, Department of Chemistry, Selcuk University,Faculty of Science, Konya, TURKEY|S. Yildiz,Department of Chemistry, Selcuk University,Faculty of Science, Konya, TURKEY|E. Ozcan, Department of Chemistry,Selcuk University,Faculty of Science, Konya, TURKEY|CURRENT CATEGORY: Metals and Nucleic AcidsABSTRACT BODY: Abstract Body: DNA is the primary cellular target for studies with small molecules of biological importance likecarcinogens and several classes of drugs. In recent years, there has also been a growing interest in exploring theinteraction of small molecules with calf thymus DNA (Ct-DNA) and PCR products regards to specific or target genes inmany fields, such as molecular biology, biotechnology and medical diagnosis [1-3]. Therefore, identifying smallmolecules that are capable of binding and cleaving DNA have also attracted considerable. anti-chloroglyoxime was prepared according to the literature procedure [4]. Genomic DNA extraction from blood of thepatients was carried and vitamin D receptor gene amplifed by polymerase chain reaction (PCR) [5]. Ct-DNA,oligonucleotite and VDR gene were mixed with 10 mM of anti-chloroglyoxime in DMF:water (1:1). Ct-DNA and oligonucleotite were mixed with 10 mM of anti-chloroglyoxime. As a result of the binding of ligand tonucleic acids, fluorescence intensity of nucleic acids increased by addition of anti-chloroglyoxime. Highestfluorescence intensity was detected at 455 and 507 nm of excitation and emission wavelengths. In this study, welabeled VDR gene by anti-chloroglyoxime. DNA extracted from blood was amplified in thermal cycler under the givenPCR condition in the method described by using TaqI primers [5]. PCR product corresponds to the VDR gene at aconcentration range of 0.1-0.6 ng mL-1 reacted with anti-chloroglyoxime and emission spectra was scanned at 455and 507 nm of excitation and emission wavelengths. References[1] R.F. Pasternack, E.J. Gibbs, J.J. Villafranca, Biochemistry 22 (1983) 2406.[2] C.V. Kumar, E.H. Asuncion, J. Am. Chem. Soc. 115 (1993) 8547.[3] O.V. Petrauskene, S. Schmidt, A.S. Karyagina, I.I. Nikolskaya, E.S. Gromova, D. Cech, Nucleic Acids Res. 23(1995) 2192.[4] H. Brintzinger, R. Titzmann, Chem. Ber. 85 (1952) 344.[5] H.C. Vural and E. Maltas, Genet. Mol. Res. 11 (2012) 582.(No Image Selected)

CONTROL ID: 1718608TITLE: Interaction of Platinum compounds with RNAAUTHORS/INSTITUTIONS: M. Zampakou, D. Donghi, University of Zurich, Institute of Inorganic Chemistry, Zurich,SWITZERLAND|CURRENT CATEGORY: Metals and Nucleic AcidsABSTRACT BODY: Abstract Body: Nucleic acids represent an important target for many anticancer drugs and we are currentlyinvestigating the way in which platinum anticancer drugs interact with RNA. These drugs are normally thought to exerttheir activity upon covalent binding to DNA purine nitrogens.[1] Nevertheless in recent years potential alternativebinding partners have been explored, including RNA.[2]The interaction of platinum drugs with DNA is rather well studied,[3] however, surprisingly little is known about theirinteraction with RNA. It has already been reported that some RNA dependent activities, are inhibited uponadministration of platinum drugs, but still little is known on the effects of platinum on RNA biology.[4]In order to understand the effect of platinum drugs on RNA structure and activity we use as a model RNA a 27nucleotide long hairpin derived from the mitochondrial group II intron ribozyme Sc.ai5γ. The chosen RNA containsstructural features widespread in RNAs and its NMR structure in solution is known,[5] making easier a detailedinvestigation of the structural changes upon platinum drug interaction. At the moment, we are optimizing theplatination conditions and characterizing the platinated adducts by mass spectrometry, circular dichroism and thermalmelting studies. The next step is then to obtain high amounts of pure platinated samples which can be used forstructural evaluation by NMR spectroscopy. Acknowledgements: Financial support by the Swiss National Science Foundation (Ambizione fellowshipPZ00P2_136726 to DD), by the University of Zurich and within the COST Action CM1105 is gratefully acknowledged. [1]R.A. Alderden, M.D. Hall, T.W. Hambley, J. Chem. Educ. 2006, 83(5), 728-734[2]E.G. Chapman,V. De Rose J. Am. Chem. Soc. 2010, 132(6), 1946-1952[3]A.M. Pizzaro, P.J. Sadler, Biochimie, 2009, 91(10), 1198-1211[4]E.G. Chapman, A.A. Hostetter, M.F. Osborn, A.L. Miller, V. J. DeRose, Met. Ions Life Sci. 2011, 9, 347-377[5]D. Donghi, M. Pechlaner, R.K.O.Sigel, unpublished(No Image Selected)

CONTROL ID: 1719015TITLE: DNA binding mode and selectivity of Cu-isaepy complexes assessed by ESI-MS and CD studies with 6-mers.AUTHORS/INSTITUTIONS: J. Madureira, P. Di Mascio, A.C. Ferreira, Química Fundamental, Instituto de Química daUniversidade de São Paulo, São Paulo, SP, BRAZIL|CURRENT CATEGORY: Metals and Nucleic AcidsABSTRACT BODY: Abstract Body: A copper(II) complex with isaepy ((2-oxindol-3-yl-imino)-2-(2-aminoethyl)pyridine-N) is known to inhibitproliferation of cancerous cell lines and induce apoptosis, after DNA damage that cannot be repaired. While thecomplex is able to catalyze the formation of ROS at the mitochondria, several author studies with DNA show that itsstructure remains intact (no oxidative damage to 2-deoxy-ribose, phosphate hydrolysis and moderate nuclease activityonly). Biophysical studies by CD, fluorescence and agarose gel electrophoresis suggested a major groove-bindingmode, since the complex presented a modest ability to displace ethidium bromide and distamycin did not interfere withcleavage of plasmidial DNA. The high volumetry of the complex and the possibility to establish hydrogen bonds wasalso consistent with such assumption.In order to clarify the binding mode, we decided to revisit DNA interactions, paying attention to its composition andsequence. We performed ESI MS(-) and MS/MS studies with eight auto-complementary 6-mers in conditions favoringdouble-helix (ds) formation, while control drugs were also studied to confirm the validity of the mechanism assigned ingas phase. Preliminary studies in MeCN and MeCN/H2O 3:1 show an equilibrium between two forms of the complex(scheme 1), with aqueous media largely favoring the second one. This form is also the only that binds the ds(6-mer) inMeCN/20 mM TEAA 3:1 and shows a clear preference for those rich in guanine nucleobases. No interaction with dswas detected when pure AT or oligomers with no sequential GXG or GG sequences are present. MS/MS spectraindicate an intercalation mechanism. Solution studies (CD and thermal denaturation) with all the 6-mers were alsoperformed, which support the proposed binding mechanism for the complex in the gas phase. The main reason whyfluorescence and CD results seem to indicate a moderate DNA intercalation ability is then the high selectivity of thecomplex.

Scheme 1

CONTROL ID: 1719839TITLE: pH-dependent discrimination of silver(I)-mediated phenanthroline:pyrimidine base pairsAUTHORS/INSTITUTIONS: P. Scharf, J. Müller, Institute of Inorganic and Analytical Chemistry, WestfälischeWilhelms-Universität Münster, Münster, GERMANY|CURRENT CATEGORY: Metals and Nucleic AcidsABSTRACT BODY: Abstract Body: Functionalization of the nucleic acids DNA and GNA by introduction of artificial nucleobases is agrowing field concerning several chemical disciplines (GNA = glycol nucleic acid). Especially the use of ligands asnucleobases resulting in metal-mediated base pairs offers the opportunity to modify the properties of thesesupramolecules especially for applications in nanotechnology regarding conductivity or magnetism.[1-4]We report the synthesis of a novel GNA building block of the ligand 1H-imidazo[4,5-f]-[1,10]phenanthroline (P), itsintegration into a DNA oligonucleotide and the formation of a chimeric metal-mediated GNA/DNA base pairincorporated into a DNA double helix. The base pair consists of a bidentate phenanthroline derivative and a naturalpyrimidine nucleobase (thymine T or cytosine C).Temperature-dependent UV-spectroscopic data show that the P:C and the P:T base pairs exhibit the same thermalstability irrespective of the pH. After addition of Ag(I) the data indicate the formation of a Ag(I)-mediated P:C base pairwhile the P:T base pair is significantly destabilized. Furthermore a strong influence of the pH on the stability of theresulting metal-mediated base pairs is observed. [1]P. Scharf, J. Müller, ChemPlusChem 2013, 78, 20-34.[2]L. Zhang, A. E. Peritz, P. J. Carroll, E. Meggers, Synthesis 2006, 4, 645-653.[3]M. K. Schlegel, L. Zhang, N. Pagano, E. Meggers, Org. Biomol. Chem. 2009, 7, 476-482.[4]K. Seubert, C. Fonseca Guerra, F. M. Bickelhaupt, J. Müller, Chem. Commun. 2011, 47, 11041-11043. Acknowledgement: DFG (SFB 858)

CONTROL ID: 1719984TITLE: Structure and metal-ion binding sites of the human CPEB3 ribozyme - the first insightAUTHORS/INSTITUTIONS: M. Rowinska-Zyrek, M. Skilandat, R. Sigel, University of Zurich, Zurich, SWITZERLAND|CURRENT CATEGORY: Metals and Nucleic AcidsABSTRACT BODY: Abstract Body: The CPEB3 ribozyme is a highly conserved, mammalian, self cleaving, non-coding RNA located in thesecond intron of the CPEB3 gene [1]. Most of the available knowledge about this ribozyme is based on comparativestudies with the structurally and biochemically similar HDV (Hepatitis Delta Virus) ribozyme.; both can be folded in thesame overall pseudoknot structure [1,2] and show strong parallels in their catalysis and metal-ion requirements [1,3].In this work, the solution structure of a well-conserved motif of the CPEB3 ribozyme, the P4 region, is determined byNMR spectroscopy, and the binding sites and impact of the addition of Mg2+ and [Co(NH3)6]3+ (a spectroscopicprobe for Mg(H2O)62+) are discussed. The detailed knowledge about the P4 structure and metal ion-bindingpreferences thus brings us closer to understanding the CPEB3 ribozyme’s function in the cell.Moreover, some insight into the overall structure of the ribozyme is provided by the results of NMR studies of asegmented, partially labeled construct. Financial support by the Swiss National Science Foundation and from a Sciex post doctoral grant (Grant No. 11.156)to MRZ is gratefully acknowledged. [1]K. Salehi-Ashtiani, A. Luptak, A. Litovchick, J.W. Szostak., Science, 2006, 313, 1788.[2]C. Webb, N.J. Riccitelli, D.J. Ruminski, A. Luptak, Science, 2009, 326, 953.[3]D.M Chahadalavada, E.A. Gratton, P.C. Bevilacqua, Biochemistry, 2010, 49, 5321.(No Image Selected)

CONTROL ID: 1720912TITLE: Binding of nucleotides to anti-chloroglyoxime for DNA labelingAUTHORS/INSTITUTIONS: S. Yildiz, Chemistry, Selcuk University, Konya, TURKEY|E. Maltas, Department ofChemistry, Selcuk University,Faculty of Science, Konya, TURKEY|M. Findik, Department of Chemistry, SelcukUniversity,Faculty of Science, Konya, TURKEY|E. Ozcan, Department of Chemistry, Selcuk University,Faculty ofScience, Konya, TURKEY|CURRENT CATEGORY: Metals and Nucleic AcidsABSTRACT BODY: Abstract Body: Immunofluorescence staining techniques, real time polymerase chain reaction (RT-PCR) andfluorescence microscopy are powerful tool for molecular biologist and cell biologist. The natural fluorescence intensityof nucleic acids is so weak The detection and visulization of nucleic acids by fluorescent dyes such as 4,6-diamidine-2-phenyl indole dihydrochloride (DAPI), EtBr, SYBR Green and PicoGreen has become increasingly important for alarge number of biological, analytical and diagnostic application [1-4].In this study, the interaction of anti-chloroglyoxime as ligand with nucleotides was identified via fluorescencespectroscopy. To explain binding mechanism, IR-spectroscopy was also used for products regards to the reactionsbetween ligand and four DNA nucleobases; adenine, guanine, cytosine and timin. anti-Chloroglyoxime was preparedaccording to the literature procedure [5]. A solution containing anti-chloroglyoxime (2.5 mmol) was added to 2.5 mmolof nucleotides. The effect of ligand and nucleotide concentration on fluorescence intensity was investigated in theconcentration range of 1–30 mM. Where adenine exhibited high fluorescence intensity at 301 and 380 nm, the anti-adenineglyoxime shifted to 457 nm and 515 nm of excitation and emission wavelengths after addition of anti-chloroglyoxime at pH 7. anti-guanineglyoxime and anti-cytosineglyoxime exhibited at 515 nm of emission wavelengthat the same excitation wavelengths with that of anti-adenineglyoxime when guanine and cytosine reacted with anti-chloroglyoxime. The data indicated that anti-guanineglyoxime showed highest intensity when compared with those ofother anti-nucleobaseglyoximes. Timin didn’t bind to the ligand. References[1] J. Kapuscinski, B. Skoczylas, Anal. Biochem. 83 (1977) 252.[2] J.B. LePecq, C. Paoletti, Anal. Biochem. 17 (1966) 100.[3] U. Karsten, A. Wollenberger, Anal. Biochem. 77 (1977) 464.[4] P. Krishnamoorthy, P. Sathyadevi, Alan H. Cowley, Rachel R. Butorac, N. Dharmaraj Europ. J. Med. Chem. 46(2011) 3376.[5] C. Liu, J. Zhou, Q. Li, L. Wang, Z. Liao, H. Xu, J. Inorg, Biochem 75 (1996) 233.(No Image Selected)

CONTROL ID: 1721259TITLE: Ferrocene Nucleic Acid: An Organometallic DNA MimicAUTHORS/INSTITUTIONS: J. Duprey, H.V. Nguyen, Z. Zhao, A. Sallustrau, S.L. Horswell, A. Mulas, L. Male, J.H.Tucker, School of Chemistry, University of Birmingham, Birmingham, UNITED KINGDOM|CURRENT CATEGORY: Metals and Nucleic AcidsABSTRACT BODY: Abstract Body: The use of DNA as a supramolecular scaffold is a highly promising component of nanoscalearchitecture. One particularly attractive approach in the field of DNA nanotechnology and synthetic biology involvessupplementing and/or substituting the natural nucleosides with alternative moieties such as chromophoric or metal-based units that could impart to the system unique properties that are not otherwise attainable.In our group we are interested in functionalizing DNA with moieties that can provide information about DNArecognition events by means of electro- or photochemical output.[1] In particular we are focusing on incorporatingferrocene, a redox active reporting group, into DNA and exploiting its properties for DNA hybridization sensing,electron transfer measurements and novel structural motifs.We will present a family of enantiomerically pure ferrocene based oligonucleotide analogues where thephosphodiester-sugar backbone is wholly or partially replaced by ferrocene units (see figure). These neworganometallic DNA sequences[2] (which we have termed ferrocene nucleic acid or FcNA) show high solutionstability, quasi-reversible electrochemical behavior and we are currently exploring the functional properties of FcNA-DNA oligomeric conjugates with a range of target sequences in an effort to probe their hybridization characteristicsand determine their utility and scope for DNA nanotechnology and bioinorganic chemistry. [1] J. Manchester, D. M. Bassai, J.-L. H. A. Duprey, L. Giordano, J. Vyle, Z. Zhao and J. Tucker, J. Am. Chem. Soc.2012, 134, 10791-10794[2] H. Nguyen, Z. Zhao, A. Sullustre, S. L. Horsewell, L. Male, A. Mulas and J. Tucker, Chem. Commun. 2012, 48,12165-12167.

CONTROL ID: 1721778TITLE: Targeting quadruplex nucleic acids with metal complexesAUTHORS/INSTITUTIONS: A. Leczkowska, R. Vilar, Department of Chemistry, Imperial College London, London,UNITED KINGDOM|CURRENT CATEGORY: Metals and Nucleic AcidsABSTRACT BODY: Abstract Body: The range of possible biologically relevant conformations of DNA extends far beyond the canonical Bstructure. G-quadruplex DNA is of particular interest amongst these topologies as this form of DNA has been found inthe promoter regions of genes and at the terminal regions of chromosomes. There is also significant evidencesuggesting that it may play important roles in key genomic processes such as transcriptional regulation. Therefore, ithas been proposed that small molecules that can selectively sense, stabilise or alter such structures in vivo could actas novel therapeutic agents and/or unique probes for elucidating information from DNA transactions within the humangenome.[1]Our group has previously demonstrated that metal complexes can act as excellent stabilisers of G-quadruplex DNAtopologies. Our square-planar, mono- and bimetallic complexes not only bind strongly and selectively to quadruplexDNA but also inhibit telomerase activity and exhibit significant cytotoxic effects in human cancer cell lines.[2,3]Herein we will present a library of new metal complexes with different structural topologies, their remarkable effects onquadruplex DNA structures (e.g. c-MYC, h-telo, c-kit) and in cells. More specifically, we will show how subtle controlover DNA recognition properties can be achieved by judicious selection of metal ions and substituents on the ligandbackbone. The photophysical properties of these complexes and how they can be exploited to probe DNA structuresin vivo as well as the cytotoxic activity our compounds will also be discussed. References[1] S. Balasubramanian, L.H. Hurley, S. Neidle, Nat. Rev. Drug Discov., 2011, 10, 261; G. Biffi, D. Tannahill, J.McCafferty and S. Balasubramania, Nature Chem., 2013, 5, 182;[2] J.E. Reed, A. Arola-Arnal, S. Neidle and R.Vilar, J. Am. Chem. Soc., 2006, 128, 5992; K. Suntharalingam, A.J.P.White and R. Vilar, Inorg. Chem., 2009, 48, 9427; K. Suntharalingam, A.J.P. White and R. Vilar, Inorg. Chem., 2010,49, 8371;[3] N.H. Campbell, N.H. Abd Karim, G.N. Parkinson, M. Gunaratnam, V. Petrucci, A.K. Todd, R. Vilar and S. Neidle, J.Med. Chem., 2012, 55, 209.(No Image Selected)

CONTROL ID: 1722002TITLE: Interactions of NAMI-A with tRNAAUTHORS/INSTITUTIONS: K.M. Holman, E. Johnson, E. Cazares, R. Josephson, S.R. Kirk, Chemistry, WillametteUniversity, Salem, Oregon, UNITED STATES|CURRENT CATEGORY: Metals and Nucleic AcidsABSTRACT BODY: Abstract Body: NAMI-A, [ImH][trans-RuCl4(DMSO)(Im)], is an effective anti-metastatic agent, yet its primary cellulartarget is not known. Previous studies by our group1 showed that in the presence of NAMI-A, Ru-RNA adducts form invitro and in vivo, and these adducts form to a greater extent in slightly acidic, reducing environments like those foundin cancerous cells. In this work, we used fluorescence spectroscopy and PAGE to further investigate the interactionsbetween NAMI-A and nucleic acids. Measurements of both intrinsic and extrinsic fluorophores indicate that NAMI-Ainteracts with tRNAPhe in a manner that disrupts the normal tertiary structure. Additionally, reduced NAMI-A appearsto compete for binding sites differently than NAMI-A in its Ru(III) form. PAGE analysis was used to explore theinteractions between NAMI-A and tRNAPhe under various experimental conditions including pH, incubation time,NAMI-A concentration, and the reduction of NAMI-A by ascorbate. Consistent with fluorometric results, gels run underboth native and denaturing conditions suggest that the interaction between NAMI-A and tRNAPhe is pH dependent.In addition, NAMI-A in the oxidized and reduced forms appear to interact differently with tRNAPhe. Combined, ourresults suggest a role for tRNA as a putative cellular target of NAMI-A. 1A.A. Hostetter, M.L. Miranda, V.J. DeRose, K.L. McFarlane Holman J. Biol. Inorg. Chem. 2011, 16, 1177-1185.(No Image Selected)

CONTROL ID: 1770436TITLE: FORMATION OF GLUTATIONYL DINITROSYL IRON COMPLEXES DOES NOT ALLEVIATE IRONGENOTOXICITYAUTHORS/INSTITUTIONS: H. Lewandowska, T. Stepkowski, J. Sadlo, M. Kruszewski, Institute of Nuclear Chemistryand Technology, Warsaw, POLAND|M. Kruszewski, Institute of Agricultural Medicine, Lublin, POLAND|CURRENT CATEGORY: Metals and Nucleic AcidsABSTRACT BODY: Abstract Body: Dinitrosyl iron (I) complexes (DNIC), intracellular NO donors, are important factors in nitric oxide-dependent regulation of cellular metabolism and signal transduction. It has been shown that iron ions diminish toxicactivity of NO and vice versa. To gain insight into the possible genotoxic effects of DNIC, we examined the interactionof glutationyl dinitrosyl iron complexes (GS-DNIC) with DNA. The effect of GS-DNIC formation on iron ionsgenotoxicity was confirmed by plasmid nicking assay. Treatment of pUC19 plasmid with increasing amounts of GS-DNIC in the range of 1 μM - 1 mM was performed. It was shown, that after elimination of the traces of chelatable/labileiron by DFO the effect of GS-DNIC is protective. The physiochemical nature of the DNA-(GS-DNIC) interaction wasstudied with circular dichroism. Our results indicate that GS-DNIC changes in dose dependent manner theconformation of DNA molecule at pH 6 in 10 mM phosphate buffer, via an interaction of electrostatic character.(No Image Selected)