Crystal structure of the nucleoside 2′-deoxyguanosine dimethyl sulfoxide disolvate

The title compound, C10H13N5O4.2C2H6OS, which is of interest with respect to its biological activity, at 183 K has orthorhombic P212121 crystal symmetry. The structure displays a network of intermolecular N—H...N, N—H...O and O—H...O hydrogen bonds. 2′-Deoxyguanosine molecules are linked to each other and to the two dimethyl sulfoxide solvent molecules by hydrogen bonding

Multifunctional Cyclopentadienes as a Scaffold for Combinatorial Bioorganometallics in [(η5-C5H2R1R2R3)M(CO)3] (M=Re, 99mTc) Piano-Stool Complexes

Multifunctional cyclopentadiene (Cp) ligands and their rhenium and 99mTc complexes were prepared by a versatile synthetic route. The properties of these Cp ligands can be tuned on demand, either during their synthesis (variation of R1) or through post-synthetic functionalization with two equal or different vectors (V1 and V2). Variation of these groups enables a combinatorial approach in the synthesis of bioorganometallic complexes. This is demonstrated by the preparation of Cp ligands containing both electron-donating and electron-withdrawing groups at the R1 position and their subsequent homo- or heterofunctionalization with biovector models (benzylamine and phenylalanine) under standard amide bond-formation conditions. All ligands can be coordinated to the fac-[Re(CO)3]+ and fac-[99mTc(CO)3]+ cores to give tetrafunctional complexes in straightforward and functional-group-tolerant procedures. The 99mTc complexes were prepared in one step, in 30 min, and under aqueous conditions from generator-eluted [99mTcO4]-

Crystal structures of B-DNA dodecamer containing the epigenetic modifications 5-hydroxymethylcytosine or 5-methylcytosine

5-Hydroxymethylcytosine (5-hmC) was recently identified as a relatively frequent base in eukaryotic genomes. Its physiological function is still unclear, but it is supposed to serve as an intermediate in DNA de novo demethylation. Using X-ray diffraction, we solved five structures of four variants of the d(CGCGAATTCGCG) dodecamer, containing either 5-hmC or 5-methylcytosine (5-mC) at position 3 or at position 9. The observed resolutions were between 1.42 and 1.99 Å. Cytosine modification in all cases influences neither the whole B-DNA double helix structure nor the modified base pair geometry. The additional hydroxyl group of 5-hmC with rotational freedom along the C5-C5A bond is preferentially oriented in the 3′ direction. A comparison of thermodynamic properties of the dodecamers shows no effect of 5-mC modification and a sequence-dependent only slight destabilizing effect of 5-hmC modification. Also taking into account the results of a previous functional study [Münzel et al. (2011) (Improved synthesis and mutagenicity of oligonucleotides containing 5-hydroxymethylcytosine, 5-formylcytosine and 5-carboxylcytosine. Chem. Eur. J., 17, 13782−13788)], we conclude that the 5 position of cytosine is an ideal place to encode epigenetic information. Like this, neither the helical structure nor the thermodynamics are changed, and polymerases cannot distinguish 5-hmC and 5-mC from unmodified cytosine, all these effects are making the former ones non-mutageni

Derivatives of Sodium Boranocarbonate as Novel CO-Releasing Molecules (CO-RMs)

Despite the apparent and well-known toxic effects of carbon monoxide (CO), studies on the intriguing biological roles of this molecule are rapidly emerging. Recent investigations have brought to the limelight various physiological effects of CO which include, among others, vasorelaxation and inhibition of organ rejection after transplantation. The importance of CO in biology can be compared with another gas, nitric oxide (NO), an essential and ubiquitous signalling molecule. This parallelism led to the tantalising concept of using CO for therapeutic purposes wherein compounds that transport and deliver this gas to a target tissue would clearly facilitate both the clinical feasibility and the specificity of CO therapy. Sodium boranocarbonate, Na[H3 BCO2H] (1) was the first water-soluble and non-transition metal containing CO-releasing molecule (CO-RM) to be identified. In order to tune the rate of CO release, we modified 1 and synthesised and characterized various derivatives which release CO under physiological conditions but at rates different from the parent compound 1. The synthesis, structure and CO-releasing properties of ester and amide derivatives of 1 will be presented together with some biological studies carried out with a selection of the compounds

Potent PBS/Polysorbate-Soluble Transplatin-Derived Porphyrin-Based Photosensitizers for Photodynamic Therapy

In this study, we addressed an important drawback of our previously reported tetraplatinated (metallo)porphyrin-based photosensitizers (PSs) for photodynamic therapy (PDT), namely, the poor solubility in aqueous media. We aimed to create tetraplatinated porphyrin-based PSs that are soluble in aqueous media modified with polysorbate (Tween) and do not need to be pre-dissolved in organic solvents. A structural optimization of the previously reported PSs resulted in the synthesis of an extremely potent novel porphyrin-based PS. The novel PS displays effective phototoxicity upon light irradiation against multicellular tumor spheroids and has a phototoxic index (PI) of 6030 in HeLa cells. This PI value is, to the best of our knowledge, the highest value reported for any porphyrin so far

Polar Substituents Enable Efficient Catalysis for a Class of Cobalt Polypyridyl Hydrogen Evolving Catalysts

A series of structurally related, acyclic cobalt tetrapyridyl hydrogen evolving catalysts (HEC) were prepared and characterized. The common motif, di(2,2′-bipyridin-6-yl)-methane, was derivatized at the bridging methylene to include a carbonyl group (L1), a hydroxy (L2), a methyl and a hydroxy (L3), a 1,1′-biphenyl-2,2′-diyl (L4), a hydroxy and a phenyl (L5) or a hydroxy and a pyrid-6-yl group. These catalysts were compared with the known HEC [Co(appy)Br]Br. Photo- and electrochemistry showed a distinct influence of the bridging position on rates and stabilities of the hydrogen evolution reaction (HER). Apolar ligands resulted in inferior catalytic performance as compared to HECs with polar substituents. Electrochemically, [Co(L1)Br2] was shown to be converted to [Co(L2)Br2] in catalysis. The best catalyst made more than 10’000 turnovers, albeit at an overpotential of 600 mV. Additional pH dependent mechanistic aspects were elucidated by cyclic voltammetry

Structural analysis of Cu(II) ligation to the 5′-GMP nucleotide by pulse EPR spectroscopy

Simple copper salts are known to denature poly d(GC). On the other hand, copper complexes of substituted 1,4,7,10,13-pentaazacyclohexadecane-14,16-dione are able to convert the right-handed B form of the same DNA sequence to the corresponding left-handed Z form. A research program was started in order to understand why Cu(II) as an aquated ion melts DNA and induces the conformational change to Z-DNA in the form of an azamacrocyclic complex. In this paper, we present a continuous wave and pulse electron paramagnetic resonance study of the mononucleotide model system Cu(II)-guanosine 5′-monophosphate . Pulse EPR methods like electron-nuclear double resonance and hyperfine sublevel correlation spectroscopy provide unique information about the electronic and geometric structure of this model system through an elaborate mapping of the hyperfine and nuclear quadrupole interactions between the unpaired electron of the Cu(II) ion and the magnetic nuclei of the nucleotide ligand. It was found that the Cu(II) ion is directly bound to N7 of guanosine 5′-monophosphate and indirectly bound via a water of hydration to a phosphate group. This set of experiments opens the way to more detailed structural characterization of specifically bound metal ions in a variety of nucleic acids of biological interest, in particular to understand the role of the metal-(poly)nucleotide interactio

Multitopic 3,2′:6′,3′′-terpyridine ligands as 4-connecting nodes in two-dimensional 4,4-networks

The tetratopic 1,4-bis(2-phenylethoxy)-2,5-bis(3,2′:6′,3′′-terpyridin-4′-yl)benzene (1) and 1,4-bis(3-phenylpropoxy)-2,5-bis(3,2′:6′,3′′-terpyridin-4′-yl)benzene (2) ligands have been prepared and fully characterised. Combination of ligand 1 or 2 and [M(hfacac)2]·xH2O (M = Cu, x = 1; M = Zn, x = 2) under conditions of crystal growth by layering led to the formation of [Cu2(hfacac)4(1)]n·3.6n(1,2-Cl2C6H4)·2nCHCl3, [Zn2(hfacac)4(1)]n·nMeC6H5·1.8nCHCl3, [Cu2(hfacac)4(2)]n·nMeC6H5·2nH2O, [Cu2(hfacac)4(2)]n·2.8nC6H5Cl and [Cu2(hfacac)4(2)]n·2n(1,2-Cl2C6H4)·0.4nCHCl3·0.5nH2O. For each compound, single-crystal X-ray analysis revealed the assembly of a planar (4,4)-net in which the tetratopic ligands 1 or 2 define the nodes. The metal centres link two different bis(3,2′:6′,3′′-tpy) ligands via the outer pyridine rings; whereas copper(II) has N-donors in a trans-arrangement, zinc(II) has them in cis. This difference between the copper(II) and zinc(II) coordination polymers modifies the architecture of the assembly without changing the underlying (4,4)-network

Multitopic 3,2′:6′,3′′-terpyridine ligands as 4-connecting nodes in two-dimensional 4,4-networks

The tetratopic 1,4-bis(2-phenylethoxy)-2,5-bis(3,2′:6′,3′′-terpyridin-4′-yl)benzene (1) and 1,4-bis(3- phenylpropoxy)-2,5-bis(3,2′:6′,3′′-terpyridin-4′-yl)benzene (2) ligands have been prepared and fully characterised. Combination of ligand 1 or 2 and [M(hfacac)2]·xH2O (M = Cu, x = 1; M = Zn, x = 2) under conditions of crystal growth by layering led to the formation of [Cu2(hfacac)4(1)]n·3.6n(1,2-Cl2C6- H4)·2nCHCl3, [Zn2(hfacac)4(1)]n·nMeC6H5·1.8nCHCl3, [Cu2(hfacac)4(2)]n·nMeC6H5·2nH2O, [Cu2(hfacac)4(2)]n·2.8nC6H5Cl and [Cu2(hfacac)4(2)]n·2n(1,2-Cl2C6H4)·0.4nCHCl3·0.5nH2O. For each compound, single-crystal X-ray analysis revealed the assembly of a planar (4,4)-net in which the tetratopic ligands 1 or 2 define the nodes. The metal centres link two different bis(3,2′:6′,3′′-tpy) ligands via the outer pyridine rings; whereas copper(II) has N-donors in a trans-arrangement, zinc(II) has them in cis. This difference between the copper(II) and zinc(II) coordination polymers modifies the architecture of the assembly without changing the underlying (4,4)-networ

Synthesis and Photophysical Evaluation of 3,3’‐Nitrogen Bis‐Substituted <i>fac</i>‐[Re(CO)₃(Diimine)Br] Complexes

The preparations, photophysical and electrochemical properties of a series of fac‐[Re(CO)$_{3}$(diimine)Br] complexes are presented. The bipyridine (bpy) based diimine ligands feature symmetrical and asymmetrical 3,3’‐diamino‐2,2’‐bipyridine substitution patterns. Photophysical and electrochemical properties of these complexes are tunable, depending on their organic diimine framework. Introduction of a distal urea bridge via the 3,3’‐substitution pattern led to prolonged phosphorescence lifetimes without a significant change in absorbance and phosphorescence emission wavelengths. Reversible electrochemical bipyridine reduction remained largely unchanged by this derivatization