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In the field of nucleic acid therapy there is major interest in the development of libraries of DNA-reactive small molecules which are tethered to vectors that recognize and bind specific genes. This approach mimics enzymatic gene editors, such as ZFNs, TALENs and CRISPR-Cas, but overcomes the limitations imposed by the delivery of a large protein endonuclease which is required for DNA cleavage. Here, we introduce a chemistry-based DNA-cleavage system comprising an artificial metallo-nuclease (AMN) that oxidatively cuts DNA, and a triplex-forming oligonucleotide (TFO) that sequence-specifically recognises duplex DNA. The AMN-TFO hybrids coordinate CuII ions to form chimeric catalytic complexes that are programmable – based on the TFO sequence employed – to bind and cut specific DNA sequences. Use of the alkyne-azide cycloaddition click reaction allows scalable and high-throughput generation of hybrid libraries that can be tuned for specific reactivity and gene-of-interest knockout. As a first approach, we demonstrate targeted cleavage of purine-rich sequences, optimisation of the hybrid system to enhance stability, and discrimination between target and off-target sequences. Our results highlight the potential of this approach where the cutting unit, which mimics the endonuclease cleavage machinery, is directly bound to a TFO guide by click chemistry.

The antimony(iii) complex of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate (DOTA) has been prepared and its exceptionally low stability observed. The Sb(iii) ion in Na[Sb(DOTA)]·4H

In the present work, we report a detailed investigation of four supramolecular coordination complexes, Zn(Quino)2(CH3OH)2 2, Zn(Quino)2H2O 3, Mn(Quino)2(CH3OH)2 4 and Ca(Quino)2(CH3OH)2 5, obtained from the self-assembling of Zn(II), Mn(II) and Ca(II) acceptors with the N-phenyl-4-hydroxyquinoline ligand donor QuinoH 1, possessing the β,β′-diketonate moiety. The structure of the supramolecular arrangement of the isolated complexes have been investigated by single crystal X-ray crystallography. The synthetic N-phenyl quinolone-linker that forms a π–π stacking supramolecular synthon with the coordination preferences of metal ions has been used to construct coordination driven self-assembled “metallosupramolecular” architectures.

The antimony(III) complex of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate (DOTA) has been prepared and its exceptionally low stability observed. The Sb(III) ion in Na[Sb(DOTA)] 4H2O shows an approximately square antiprismatic coordination geometry that is close to superimposable to the Bi(III) geometry in [Bi(DOTA)]- in two phases containing this anion, Na[Bi(DOTA)] 4H2O, [H3O][Bi(DOTA)] H2O for which structures are also described. Interestingly, DOTA itself in [(H6DOTA)]Cl2•4H2O•DMSO shows the same orientation of the N4O4 metal binding cavity reflecting the limited flexibility of DOTA in an octadentate coordination mode. In 8-coordinate complexes it can however accommodate M(III) ions with rion spanning a relatively wide range from 87 pm (Sc(III)) to 117 pm (Bi(III)). The larger Bi3+ ion appears to be the best metal-ligand size match since [Bi(DOTA)]- is associated with greater complex stability. In the solution state, [Sb(DOTA)]- is extremely susceptible to transmetallation by trivalent ions (Sc(III), Y(III), Bi(III)) and, significantly, even by biologically important divalent metal ions (Mg(II), Ca(II), Zn(II)). In all cases just one equivalent is enough to displace most of the Sb(III). [Sb(DOTA)]- is resistant to hydrolysis; however, since biologically more abundant metal ions easily substitute the antimony, DOTA complexes will not be suitable for deployment for the delivery of the, so far unexploited, theranostic isotope pair 119Sb and 117Sb.

Phenanthroline ligands are important metal-binding molecules which have been extensively researched for applications in both material science and medicinal chemistry. Azobenzene and its derivatives have received significant attention because of their ability to be reversibly switched between the E and Z forms and so could have applications in optical memory and logic devices or as molecular machines. Herein we report the formation and crystal structure of a highly unusual novel diazo-diphenanthroline compound, C24H14N6O2·2CHCl3.

Organotin (IV) derivatives of carboxylate ligand, 4-(4-methoxyanilino)-4-oxobutanoic acid, have been synthesized and characterized by FTIR, NMR, CHN analysis, mass spectrometry and X-ray crystallography. Single crystal data of four compounds (1–4) displayed a distorted trigonal bipyramidal environment around Sn with the three equatorial positions occupied by alkyl group. In compounds 1–3, carboxylate oxygens of ligand play the role of a bridge between the adjacent tin atoms symmetrically giving a polymeric chain structure. In compound 4, oxygen of the amide carbonyl moiety perform the same function and bridges the adjacent tin atoms [Sn O = 2.155 (3) and 2.428 (3) A, respectively], with the three phenyl ipso-C atoms defining the trigonal plane and the axial positions occupied by O atoms [O1 Sn O3 = 177.62 (11) A]. The τ values calculated for complexes 1–4 are 0.78, 0.77, 0.82 and 0.92, respectively, also confirm the trigonal bipyramidal geometry. The antimicrobial results of the synthesized compounds illustrate their use as a potential antimicrobial agent. The DNA interaction study performed by UV–visible spectroscopy as well as by molecular docking suggests the tested compounds interact with DNA through intercalation mode. The compounds were screened for anticancer activity performed against lung carcinoma and Vero cell lines resulting in activity that is almost equivalent to that of the standard, vincristine. The biological significance of these compounds is that there affect on the normal cell line is very small i.e.

The building of robust and versatile inorganic scaffolds with artificial metallo-nuclease (AMN) activity is an important goal for bioinorganic, biotechnology, and metallodrug research fields. Here, a new type of AMN combining a tris-(2-pyridylmethyl)amine (TPMA) scaffold with the copper(II) N,N′-phenanthrene chemical nuclease core is reported. In designing these complexes, the stabilization and flexibility of TPMA together with the prominent chemical nuclease activity of copper 1,10-phenanthroline (Phen) were targeted. A second aspect was the opportunity to introduce designer phenazine DNA intercalators (e.g., dipyridophenazine; DPPZ) for improved DNA recognition. Five compounds of formula [Cu(TPMA)(N,N′)]2+ (where N,N′ is 2,2-bipyridine (Bipy), Phen, 1,10-phenanthroline-5,6-dione (PD), dipyridoquinoxaline (DPQ), or dipyridophenazine (DPPZ)) were developed and characterized by X-ray crystallography. Solution stabilities were studied by continuous-wave EPR (cw-EPR), hyperfine sublevel correlation (HYSCORE), and Davies electron–nuclear double resonance (ENDOR) spectroscopies, which demonstrated preferred geometries in which phenanthrene ligands were coordinated to the copper(II) TPMA core. Complexes with Phen, DPQ, and DPPZ ligands possessed enhanced DNA binding activity, with DPQ and DPPZ compounds showing excellent intercalative effects. These complexes are effective AMNs and analysis with spin-trapping scavengers of reactive oxygen species and DNA repair enzymes with glycosylase/endonuclease activity demonstrated a distinctive DNA oxidation activity compared to classical Sigman- and Fenton-type reagents.

CaTiO3–TiO2 composite oxide films have been employed, for the first time, as photoelectrodes in photoelectrochemical (PEC) splitting of water. The transparent methanol solutions of Ti(iPro)4 and newly synthesized calcium complex [Ca2(TFA)3(OAc)(iPrOH)(H2O)(THF)3] (1) (where TFA stands for trifluoroacetato; OAc stands for acetate; and iPrOH stands for isopropanol) were utilized for aerosol assisted chemical vapor deposition (AACVD) of the target films. The composite electrodes were deposited on fluorine doped tin oxide (FTO) coated conducting glass substrates at varying deposition temperatures of 500–600 °C. The resulting films were extensively characterized by powder X-ray diffraction, X-ray photoelectron spectroscopy, energy dispersive X-ray analysis and scanning electron microscopy. PEC responses of all the composite electrodes were studied under simulated solar irradiation of AM 1.5 G (100 mW cm−2). The CaTiO3–TiO2 photoanode formed at 600 °C showed higher photocurrent density of 610 µA cm−2 at 0.7 V versus Ag/AgCl/3 M KCl reference electrode as compared to the other two electrodes fabricated similarly with only difference of fabrication temperature (i.e., 500 and 550 °C).

Controlled bottom-up synthesis of amorphous coordination polymers with tailored metal coordination is a research field in its infancy. In this study, synthesis control was achieved to selectively prepare one-dimensional (1D) crystalline and amorphous zinc(ii)-based coordination polymers and a dimeric molecular compound, all with similar coordination geometry as evidenced by X-ray diffraction and total scattering studies. The compounds were obtained by bottom up self-assembly of Zn(ii) with terephthalate (tph2−) as linker and the enantiopure chelating ligandS-(1,2)-bis(1H-benzimidazol-2-yl)ethanol (L). The solvent and the coordination ability of the precursor zinc salt anion control the crystalline products formed by slow diffusion at room temperature: perchlorate allows isolation of the phase pure crystalline 1D polymer {[Zn(tph)(L)]·H2O·3DMF}n(1·H2O·3DMF, DMF =N,N-dimethylformamide). In contrast, zinc chloride leads to the formation of either a mixture of polymeric1·H2O·3DMF and a dimeric molecular species [Zn2Cl2(tph)(L)2]·4DMF (2·4DMF), or to the phase pure dimer2·4DMF, depending on the Zn(ii) : tphH2stoichiometry. A modified synthesis using zinc nitrate and fast precipitation by base addition results in an amorphous analogue of the 1D polymer (3). Chains of1·H2O·3DMF pack into a non-porous crystalline material with a surface area of just 6 m2g−1, while the outer surface area of amorphous polymer3is a factor of eight larger. Hence, the amorphous compound provides larger metal site accessibility for potential surface chemical reactions, while maintaining the coordination geometry of the metal sites. The temperature response of crystalline polymer1·H2O·3DMF was studied using multi-temperature single crystal X-ray diffraction (100-300 K). Thea=baxes display normal positive thermal expansion, while thecaxis remains constant with increasing temperature due to partial relaxation of the terephthalate linkers and slightly changed geometry within the individual polymer chains.

The polymeric complex trans-[Ni(acac)2(µ2-dppe)]n·2MeCN {1a, dppe = 1,2-ethylenebis(diphenylphosphine)} is sometimes transiently deposited from the reaction of [Ni(acac)2] with dppe in MeCN prior to its facile onwards air oxidation to final crystallization of a doubly-oxygenated relative, cis-[Ni(acac)2(µ2-dppeO2)]n {2, dppeO2 = 1,2-ethylenebis(diphenylphosphineoxide)}. A similar unsolvated phase of the initial polymer, trans-[Ni(acac)2(µ2-dppe)]n (1b), can be isolated from toluene. The oxidation of dppe by O2 is catalytic and dppeO2 was isolated in close to stoichiometric yields from solutions containing 5 % Ni(acac)2 relative to dppe. The reaction rate slows after a few turnovers due to inhibition by the product. The relative yields of dppeO2 are higher than those from catalytic air oxidation of methyldiphenylphosphine and triphenylphosphine and we speculate that a pathway for this reaction involves a dimetallic cooperativity enabled specifically by dppe.

Nucleic acid click chemistry was used to prepare a family of chemically modified triplex forming oligonucleotides (TFOs) for application as a new gene-targeted technology. Azide-bearing phenanthrene ligands—designed to promote triplex stability and copper binding—were ‘clicked’ to alkyne-modified parallel TFOs. Using this approach, a library of TFO hybrids was prepared and shown to effectively target purine-rich genetic elements in vitro. Several of the hybrids provide significant stabilisation toward melting in parallel triplexes (>20 °C) and DNA damage can be triggered upon copper binding in the presence of added reductant. Therefore, the TFO and ‘clicked’ ligands work synergistically to provide sequence-selectivity to the copper cutting unit which, in turn, confers high stabilisation to the DNA triplex. To extend the boundaries of this hybrid system further, a click chemistry-based di-copper binding ligand was developed to accommodate designer ancillary ligands such as DPQ and DPPZ. When this ligand was inserted into a TFO, a dramatic improvement in targeted oxidative cleavage is afforded.

A series of semicrystalline and amorphous one-dimensional (1D) polymeric chains consisting of cubane-like CoII4L4 units (L = S-1,2-bis(benzimidazol-2-yl)ethanol) and dicarboxylates were synthesized and characterized by single crystal diffraction and X-ray total scattering. The polycationic chains are composed of [Co4L4(dicarboxylate)]2+ monomeric units, while one molecular dicarboxylate counterion is balancing the charge of each monomer. The linear compound series has five members, and the crystal structures were solved for [Co4L4(tph)](tph) and [Co4L4(ndc)](ndc), where tph = terephthalate and ndc = 2,6-naphthalenedicarboxylate. Partly crystalline compounds were produced by slow assembly at elevated temperature (over days), while the amorphous compounds were formed by fast precipitation (within minutes). Pair distribution function (PDF) analysis based on X-ray total scattering data reveals the presence of the cubane-like entity in both the amorphous and semicrystalline samples. While the powders are non-porous, precipitation is a fast and versatile method to produce compounds with cubane-like centres with moderate surface areas of 17-49 m2 g-1 allowing for surface chemical reactions. The powders have a high concentration of Lewis base sites as verified by their selective adsorption of CO2 over N2. The use of an amorphous cubane-like polymer for the electrocatalytic oxygen evolution reaction was demonstrated.

We report a series of copper(II) artificial metallo-nucleases (AMNs) and demonstrate their DNA damaging properties and in-vitro cytotoxicity against human-derived pancreatic cancer cells. The compounds combine a tris-chelating polypyridyl ligand, di-(2-pycolyl)amine (DPA), and a DNA intercalating phenanthrene unit. Their general formula is Cu-DPA-N,N' (where N,N'=1,10-phenanthroline (Phen), dipyridoquinoxaline (DPQ) or dipyridophenazine (DPPZ)). Characterisation was achieved by X-ray crystallography and continuous-wave EPR (cw-EPR), hyperfine sublevel correlation (HYSCORE) and Davies electron-nuclear double resonance (ENDOR) spectroscopies. The presence of the DPA ligand enhances solution stability and facilitates enhanced DNA recognition with apparent binding constants (Kapp) rising from 105 to 107 m−1 with increasing extent of planar phenanthrene. Cu-DPA-DPPZ, the complex with greatest DNA binding and intercalation effects, recognises the minor groove of guanine–cytosine (G-C) rich sequences. Oxidative DNA damage also occurs in the minor groove and can be inhibited by superoxide and hydroxyl radical trapping agents. The complexes, particularly Cu-DPA-DPPZ, display promising anticancer activity against human pancreatic tumour cells with in-vitro results surpassing the clinical platinum(II) drug oxaliplatin.

13C solid-state MAS NMR spectra of a series of paramagnetic metal acetylacetonate complexes; [VO(acac)2] (d1, S = ½), [V(acac)3] (d2, S = 1), [Ni(acac)2(H2O)2] (d8, S = 1), and [Cu(acac)2] (d9, S = ½), were assigned using modern NMR shielding calculations. This provided a reliable assignment of the chemical shifts and a qualitative insight into the hyperfine couplings. Our results show a reversal of the isotropic 13C shifts, δiso(13C), for CH3 and CO between the d1 and d2versus the d8 and d9 acetylacetonate complexes. The CH3 shifts change from about -150 ppm (d1,2) to roughly 1000 ppm (d8,9), whereas the CO shifts decrease from 800 ppm to about 150 ppm for d1,2 and d8,9, respectively. This was rationalized by comparison of total spin-density plots and computed contact couplings to those corresponding to singly occupied molecular orbitals (SOMOs). This revealed the interplay between spin delocalization of the SOMOs and spin polarization of the lower-energy MOs, influenced by both the molecular symmetry and the d-electron configuration. A large positive chemical shift results from spin delocalization and spin polarization acting in the same direction, whereas their cancellation corresponds to a small shift. The SOMO(s) for the d8 and d9 complexes are σ-like, implying spin-delocalization on the CH3 and CO groups of the acac ligand, cancelled only for CO by spin polarization. In contrast, the SOMOs of the d1 and d2 systems are π-like and a large CO-shift results from spin polarization, which accounts for the reversed assignment of δiso(13C) for CH3 and CO.

13C solid-state MAS NMR spectra of a series of paramagnetic metal acetylacetonate complexes; [VO(acac)2] (d1, S = ½), [V(acac)3] (d2, S = 1), [Ni(acac)2(H2O)2] (d8, S = 1), and [Cu(acac)2] (d9, S = ½), were assigned using modern NMR shielding calculations. This provided a reliable assignment of the chemical shifts and a qualitative insight into the hyperfine couplings. Our results show a reversal of the isotropic 13C shifts, δiso(13C), for CH3 and CO between the d1 and d2versus the d8 and d9 acetylacetonate complexes. The CH3 shifts change from about -150 ppm (d1,2) to roughly 1000 ppm (d8,9), whereas the CO shifts decrease from 800 ppm to about 150 ppm for d1,2 and d8,9, respectively. This was rationalized by comparison of total spin-density plots and computed contact couplings to those corresponding to singly occupied molecular orbitals (SOMOs). This revealed the interplay between spin delocalization of the SOMOs and spin polarization of the lower-energy MOs, influenced by both the molecular symmetry and the d-electron configuration. A large positive chemical shift results from spin delocalization and spin polarization acting in the same direction, whereas their cancellation corresponds to a small shift. The SOMO(s) for the d8 and d9 complexes are σ-like, implying spin-delocalization on the CH3 and CO groups of the acac ligand, cancelled only for CO by spin polarization. In contrast, the SOMOs of the d1 and d2 systems are π-like and a large CO-shift results from spin polarization, which accounts for the reversed assignment of δiso(13C) for CH3 and CO.

Bimetallic oxide composite has emerged as an effective stratagem to enhance the performance of metal oxide photoanodes. ZnO–PbO composite thin films were deposited onto fluorine doped tin oxide (FTO) coated glass substrates from a newly synthesized polymeric Zn–Pb based single source precursor {ZnPb(OAc)(TFA)3(THF)2}n via aerosol-assisted chemical vapor deposition (AACVD) technique. The precursor was synthesized by the reaction of zinc acetate dihydrate (Zn(CH3CO2)2⋅2H2O), and lead acetate trihydrate (Pb(CH3CO2)2⋅3H2O) in the presence of triflouroacetic acid using THF as a solvent. The prepared complex {ZnPb(OAc)(TFA)3(THF)2}n, was characterized by FTIR, NMR, and single crystal X-ray analysis. The polymeric precursor had melting point of 72 ᴼC and decomposed at 450 ᴼC with 36.6% residue as obtained via thermogravimetry (TG/DTG). X-ray diffraction and energy-dispersive X-ray spectroscopy studies of thin films predicted a prominent growth of ZnO–PbO crystallites onto FTO substrate. FESEM analysis illustrated a homogenous and smooth surface with evenly distributed microspheres. The direct band gap of ZnO–PbO composite, estimated by UV–Vis spectroscopy is 2.40 ​eV that proves the narrowing of band gap in composite form of ZnO with PbO. Photoelectrochemical properties of the as-synthesized ZnO–PbO composite thin films investigated in the presence of 0.5 ​M aqueous NaOH solution shows photocurrent density of 705 ​μA ​cm−2 at an applied potential of +0.8 VSCE. The charge transfer dynamics of thin films were also examined using an electrochemical impedance spectroscopy (EIS) technique.

Two discrete manganese(III) coordination compounds, [Mn(L)(OCN)]2 (1) and [Mn(L′)(H2O)2][dnba]·DMF·H2O (2) bearing in situ generated Schiff base ligands H2L [H2L = N,N′-o-phenylenebis(salicylaldimine)] or H2L′ [H2L′ = N,N′-bis(salicylidene)ethylenediamine], were easily prepared by treating Mn(CH3COO)2·4H2O with salicylaldehyde and o-phenylenediamine (for 1) or ethylenediamine (for 2), and in the presence of supporting cyanate ligands or 3,5-dinitrobenzoate (dnba) counter anions, respectively. The obtained products were isolated as air-stable crystalline solids and were fully characterized by spectroscopic methods, single-crystal X-ray diffraction, topological analysis, as well as theoretical methods. The X-ray diffraction of the compound 1 reveals that the structure is dimeric with phenolic oxygen atom acting as bridge between two symmetrically equivalent Mn(III) atoms. The structure of 2 contains mononuclear cationic [Mn(L′)(H2O)2] units along with a 3,5-dinitrobenzoate anion and crystallization DMF molecule. Structural analysis indicates a distorted octahedral geometry for both complexes. Intermolecular hydrogen bonding and π–π stacking interactions are present in the lattice and play an important role in cohesion of the structures. Topological analysis of the compound 2 reveals a binodal 3,4-connected underlying 2D net with the 3,4L13 topology. Noncovalent interactions were investigated in terms of energies and geometries using theoretical calculations. Fluorescence and antibacterial properties of 1 and 2 were also investigated and discussed.

Two new phthalonitriles 1 and 2, extended with biphenylethynyl and diphenylacetylenyl, were synthesized through a combination of Corey-Fuchs and palladium-catalyzed Sonogashira coupling reactions. The structures of 1 and 2 were revealed through single-crystal X-ray analysis. Cyclotetramerization of these phthalonitriles led to the corresponding 1,4,8,11,15,18,22,25-octabutoxy-2,3,9,10,16,17,23,24-octakis(biphenyl) and (diphenylacetylenyl) phthalocyanines. The longer substituent, namely diphenylacetylenyl, is slightly more effective than biphenyl in shifting the Q band to a longer wavelength. A cathodic shift in first oxidation potential indicated the destabilization of the HOMO energy levels that results from non-peripheral substitution and extended π-conjugation.

Herein, we report the synthesis, characterisation, X-ray crystallography, and oxidative DNA binding interactions of the copper artificial metallo-nuclease [Cu(DPQ)2(NO3)](NO3), where DPQ = dipyrido[3,2-f:2&prime, 3&prime, h]quinoxaline. The cation [Cu(DPQ)2]2+ (Cu-DPQ), is a high-affinity binder of duplex DNA and presents an intercalative profile in topoisomerase unwinding and viscosity experiments. Artificial metallo-nuclease activity occurs in the absence of exogenous reductant but is greatly enhanced by the presence of the reductant Na-L-ascorbate. Mechanistically, oxidative DNA damage occurs in the minor groove, is mediated aerobically by the Cu(I) complex and is dependent on both superoxide and hydroxyl radical generation. To corroborate cleavage at the minor groove, DNA oxidation of a cytosine&ndash, guanine (5&prime, CCGG-3&prime, )-rich oligomer was examined in tandem with a 5-methylcytosine (5&prime, C5mCGG-3&prime, ) derivative where 5mC served to sterically block the major groove and direct damage to the minor groove. Overall, both the DNA binding affinity and cleavage mechanism of Cu-DPQ depart from Sigman&rsquo, s reagent [Cu(1,10-phenanthroline)2]2+, however, both complexes are potent oxidants of the minor groove.

The meta-catenated ether-based diamine monomer α,αʹ-bis(3-aminophenoxy)-p-xylene (3APX) was synthesized from dinitro precursor α,αʹ-bis(3-nitrophenoxy)-p-xylene (3NPX). FTIR, 1 H and 13 C NMR spectroscopic studies accompanied by elemental analysis were performed for structural elucidations of 3NPX and 3APX. The spatial orientations of 3APX were explored by single crystal X-ray diffraction analysis. Its crystal system was found to be monoclinic, adopting the space group P 2 1 / c . The synthesized diamine monomer (3APX) was used for preparation of new series of polyimides by reacting with three different dianhydrides (BTDA, ODPA, 6FDA). The relevant copolyimides were developed via incorporation of 4,4ʹ-methylenedianiline (MDA) in the backbone of afore-synthesized polyimides. The structures of polyimides and copolyimides were verified by FTIR and 1 H NMR spectroscopic techniques. Their properties were evaluated by dynamic and isothermal TGA (nitrogen and air atmospheres) and WAXRD studies. Polyimides displayed significantly high thermal stability as their degradation started around 400 °C and it was improved further by execution of copolymerization strategy with MDA. The 5% weight loss temperature (T 5 ) of polyimides under nitrogen atmosphere was in the range of 425–460 °C while for copolyimides it increased to 454–498 °C. Thermal decomposition in air was slower than nitrogen between 400 and 550 °C however it was accelerated above 550 °C. Isothermal TGA disclosed that copolyimides have the ability to endure elevated temperatures for extended period. WAXRD analysis showed the amorphous nature of polyimides and copolyimides.