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The synthesis of new dinuclear complexes containing linked RuII(dppz) and ReI(dppz) moieties is reported. The photophysical and biological properties of the new complex, which incorporates a N,N'-bis(4-pyridylmethyl)-1,6-hexanediamine tether ligand, are compared to a previously reported RuII/ReI complex linked by a simple dipyridyl alkane ligand. Although both complexes bind to DNA with similar affinities, steady-state and time-resolved photophysical studies reveal that the nature of the linker affects the excited state dynamics of the complexes and their DNA photocleavage properties. Quantum-based DFT calculations on these systems offer insights into these effects. While both complexes are live cells permeant, their intracellular localizations are significantly affected by the nature of the linker. Notably, one of the complexes displayed concentration-dependent localization and possesses photophysical properties that are compatible with SIM and STED nanoscopy. This allowed the dynamics of its intracellular localization to be tracked at super resolutions.

With the long-term aim of enhancing the binding properties of dinuclear RuII-based DNA light-switch complexes, a series of eight structurally related mono- and dinuclear systems are reported in which the linker of the bridging ligand has been modulated. These tethered systems have been designed to explore issues of steric demand at the binding site and the thermodynamic cost of entropy loss upon binding. An analysis of detailed spectroscopic and isothermal titration calorimetry (ITC) studies on the new complexes reveal that one of the linkers produces a dinuclear systems that binds to duplex DNA with an affinity (Kb > 107 M-1) that is higher than its corresponding monometallic complex and is the highest affinity for a non-threading bis-intercalating metal complex. These studies confirm that the tether has a major effect on the binding properties of dinuclear complexes containing nintercalating units and establishes key design rules for the construction of dinuclear complexes with enhanced

The preparation, spectroscopic characterization, structural study and magnetic investigation of three new complexes of formula [Co(bpcam)2]ClO4·dmso·H2O (1), [Co(bpcam)2]2[Co(NCS)4]·dmso·H2O (2) and [Ni(bpcam)2]·H2O (3) [Hbpcam = bis(2-pyrimidylcarbonyl)amide] are reported. Each bpcam group in 1–3 acts as a tridentate ligand being coordinated to the cobalt(III) (1 and 2)/nickel(II) (3) ions through three nitrogen atoms in a mer-arrangement. Six-coordinate cobalt(III) and nickel(II) occur in 1 and 3 respectively, whereas six-coordinate cobalt(III) and four-coordinate cobalt(II) coexist in 2. Cyclic voltammetry of 1 in acetonitrile shows the occurrence of one quasi reversible CoIII ↔ CoII process. Direct current (dc) variable-temperature magnetic susceptibility measurements on polycrystalline samples of 2 and 3 were carried out in the temperature range 1.9–295 K. The magnetic behaviour of 2 obeys to the zero-field splitting effects (DCo) of the 4A2 ground term of the pseudotetrahedral [Co(NCS)4]2− complex anion. A Curie law for a magnetically isolated nickel(II) ion in the high temperatures domain occurs for 3, the small decrease of χMT below 10 K being due zero-field splitting effects. The analysis of the magnetic susceptibility data of 2 and 3 through the spin Hamiltonian H = DM[Sz2 − S(S + 1)/3] + gMβHS [M = Co(2) and Ni(3)] led to the following set of values: gM = 2.37 (2) and 2.12 (3) and |DM| = 34.7 (2) and 1.72 cm−1 (3).

The synthesis of two new tetracationic mononuclear RuII complexes containing the tetrapyridyl [3,2-a:2',3'-c:3'',2''-h:2''',3'''-j] phenazine ligand in which the uncoordinated site has been converted into a dicationic ethylene-bipyridyldiylium unit is reported. The structure of the complexes is fully assigned through detailed NMR studies and, in one case, through an X-ray crystallography study. Voltammetry, optical spectroscopy and computational studies confirm that the bipyridyldiylium moiety has a low-lying reduction that quenches the 3MLCT-based emission usually observed in such systems. The new complexes interact with DNA in a quite different manner to their dicationic analogues: they both bind to duplex DNA with micromolar affinity through groove binding. These observations are rationalized through a consideration of their structural and electronic properties.

Using a new mononuclear “building block,” for the first time, a dinuclear RuII(dppn) complex and a heteroleptic system containing both RuII(dppz) and RuII(dppn) moieties are reported. The complexes, including the mixed dppz/dppn system, are 1O2 sensitizers. However, unlike the homoleptic dppn systems, the mixed dppz/dppn complex also displays a luminescence “switch on” DNA light-switch effect. In both cisplatin sensitive and resistant human ovarian carcinoma lines the dinuclear complexes show enhanced uptake compared to their mononuclear analogue. Thanks to a favorable combination of singlet oxygen generation and cellular uptake properties all three of the new complexes are phototoxic and display potent activity against chemotherapeutically resistant cells.

Herein we describe the DNA binding properties of two new water-soluble ruthenium complexes; experimental and computational data reveal that both complexes display dual emission from MLCT and LLCT excited states. The interaction of the new complexes with DNA was also investigated. Although one of the complexes only binds DNA though groove binding, the second complex has separate ligands capable of groove binding and intercalation. Nevertheless, it was found that both complexes interact with duplex DNA with high affinity. DNA induced distinctive changes in the emission of the complexes; although the groove binding complex only displays a modest increase in emission on binding, the complex that contains the intercalating RuII(dppz) moiety displays a large increase in MLCT-based emission on DNA binding while emission from the LLCT excited state is unaffected. This means that the complex functions as the first ratiometric sensor for DNA.

The interaction with duplex DNA of a small library of structurally related complexes that all contain a d6-metal ion coordinated to either the 2,2′:4,4′′:4′,4′′′-quaterpyridyl ligand or its methylated derivative are reported. This library is made up of a mixture of newly synthesised and previously reported systems. Despite their structural similarities the complexes display an almost 20-fold variation in binding affinities. Although effects due to the overall charge of the complexes are apparent, the differences in binding characteristics are deeper than this; indeed, in a number of cases, changes in overall charge have little effect on binding affinity. Intriguingly, despite interacting with DNA through unfused ring systems, although two of the complexes studied are groove binders, the majority are non-classical intercalators. A rationale for these effects has been obtained through a combination of experimental and computational studies.

Metal-ion-directed self-assembly has been used to construct kinetically inert, water-soluble heterometallic Ru2Re2 hosts that are potential sensors for bioanions. A previously reported metallomacrocycle and a new derivative synthesised by this approach are found to be general sensors for bioanions in water, showing an "off-on" luminescent change that is selective for nucleotides over uncharged nucleobases. Through a change in the ancillary ligands coordinated to the ruthenium centres of the host, an "off-on" sensor has been produced. Whilst this host only shows a modest enhancement in binding affinities for nucleotides relative to the other two host systems, its sensing response is much more specific. Although a distinctive "off-on" luminescence response is observed for the addition of adenosine triphosphosphate (ATP), related structures such as adenine and guanosine triphosphate (GTP) do not induce any emission change in the host. Detailed and demanding DFT studies on the ATP- and GTP-bound host-guest complexes reveal subtle differences in their geometries that modulate the stacking interactions between the nucleotide guests and the ancillary ligands of the host. It is suggested that this change in stacking geometries affects solvent accessibility to the binding pocket of the host and thus leads to observed difference in the host luminescence response to the guests.

The synthesis of, and preliminary DNA binding studies on, bimetallic complexes containing two tethered DNA intercalating [(CO)3Re(dppz)]+ metal centres is reported.

The optical response, binding parameters, and duplex DNA binding mode of water-soluble kinetically inert tetranuclear metallomacrocycles can all be controlled by judicious selection of ancillary ligands.

Reaction of 4-bromomethyl-2,6-bis(pyrazol-1-yl)pyridine with dipicolylamine yields 4-bis(pyrid-2-ylmethyl)aminomethyl-2,6-bis(pyrazol-1-yl)pyridine (L). Treatment of L with [MCl 2 (NCPh) 2 ] (M = Pd, Pt) in the presence of AgPF 6 affords [MCl(L)]PF 6 , whose palladium or platinum centre is bound exclusively by the dipicolylamino moiety of L, as established by NMR spectroscopy. The pendant dipyrazolylpyridine residue in these compounds is complexed by iron(II) to form [Fe{MCl(μ-L)} 2 ][PF 6 ] 4 (M = Pd, 1; M = Pt, 2·nH 2 O). The nitromethane solvate crystal of 1 contains low-spin iron centres at 150 K. However, dried 1 and 2·nH 2 O are predominantly high-spin at room temperature, undergoing very gradual thermal spin transitions upon cooling to ≤ 50 % completeness. The platinum compound also undergoes a thermal spin transition in CD 3 NO 2 solution, with T 1/2 = 253 K.

The interaction of the ethylene-bipyridyldiylium-naphthaphenazine dication, dqdppn, with several hexa- and octanucleotide duplexes has been studied using CD and NMR. Taken together, these studies reveal that with the hexanucleotide, dqdppn intercalates into the terminal base pair, and causes a large twisting of the terminal base pair. In contrast, with all three octanucleotides, dqdppn intercalates more centrally within the sequence. The NMR-derived structures of two of the binding complexes demonstrate that dqdppn intercalates from the major groove in an unusual 'side-on' geometry, rather than threading through the helix. An analysis of these results indicates that the preferred binding site is not sequence-specific, but primarily at the most conformationally flexible DNA step.

A family of coordination complexes has been synthesized, each comprising a ruthenium(II) center ligated by a thiacrown macrocycle, [9]aneS(3), [12]aneS(4), or [14]aneS(4), and a pair of cis-coordinated ligands, niotinamide (nic), isonicotinamide (isonic), or p-cyanobenzamide (cbza), that provide the complexes with peripherally situated amide groups capable of hydrogen bond formation. The complexes [Ru([9]aneS(3))(nic)(2)Cl]PF(6), 1(PF(6)); [Ru([9]aneS(3)) (isonic)(2)Cl]PF(6), 2(PF(6)); [Ru([12]aneS(4))(nic)(2)](PF(6))(2), 3(PF(6))(2); [Ru([12]aneS(4))(isonic)(2)](PF(6))(2), 4(PF(6))(2); [Ru([12]aneS(4)) (cbza)(2)](PF(6))(2), 5(PF(6))(2); [Ru([14]aneS(4))(nic)(2)](PF(6))(2), 6(PF(6))(2); [Ru([14]aneS(4))(isonic)(2)](PF(6))(2), 7(PF(6))(2); and [Ru([14]aneS(4))(cbza)(2)](PF(6))(2), 8(PF(6))(2) have been characterized by NMR spectroscopy, mass spectrometry, and elemental analysis. UV/visible spectroscopy shows that each complex exhibits an intense high-energy band (230-255 nm) assigned to a pi-pi* transition and a lower energy band (297-355 nm) assigned to metal-to-ligand charge-transfer transitions. Electrochemical studies indicate good reversibility for the oxidations of complexes with nic and isonic ligands (|I(a)/I(c)| = 1; DeltaEp100 mV), In contrast, complexes 5 and 8, which incorporate cbza ligands, display oxidations that are not fully electrochemically reversible (|I(a)/I(c)| = 1, DeltaEpor = 100 mV). Metal-based oxidation couples between 1.32 and 1.93 V versus Ag/AgCl can be rationalized in term of the acceptor capabilities of the thiacrown ligands and the amide-bearing ligands, as well as the pi-donor capacity of the chloride ligands in compounds 1 and 2. The potential to use these electroactive metal complexes as building blocks for hydrogen-bonded crystalline materials has been explored. Crystal structures of compounds 1(PF(6)).H(2)O, 1(BF(4)).2H(2)O, 2(PF(6)), 3(PF(6))(2), 6(PF(6))(2)CH(3)NO(2), and 8(PF(6))(2) are reported. Four of the six form amide-amide N-H...O hydrogen bonds leading to networks constructed from amide C(4) chains or tapes containing R(2)(2) (8) hydrogen-bonded rings. The other two, 2(PF(6)) and 8(PF(6)), form networks linked through amide-anion N-H...F hydrogen bonds. The role of counterions and solvent in interrupting or augmenting direct amide-amide network propagation is explored, and the systematic relationship between the hydrogen-bonded networks formed across the series of structures is presented, showing the relationship between chain and tape arrangements and the progression from 1D to 2D networks. The scope for future systematic development of electroactive tectons into network materials is discussed.

Cytostatic agents that interfere with specific cellular components to prevent cancer cell growth offer an attractive alternative, or complement, to traditional cytotoxic chemotherapy. Here, we describe the synthesis and characterization of a new binuclear RuII-PtII complex [Ru(tpy)(tpypma)Pt(Cl)(DMSO)]3+ (tpy=2,2′:6′,2′′-terpyridine and tpypma=4-([2,2′:6′,2′′-terpyridine]-4′-yl)-N-(pyridin-2-ylmethyl)aniline), VR54, which employs the extended terpyridine tpypma ligand to link the two metal centres. In cell-free conditions, VR54 binds DNA by non-intercalative reversible mechanisms (K b =1.3×105 M-1) and does not irreversibly bind guanosine. Cellular studies reveal that VR54 suppresses proliferation of A2780 ovarian cancer cells with no cross-resistance in the A2780CIS cisplatin-resistant cell line. Through the preparation of mononuclear RuII and PtII structural derivatives it was determined that both metal centres are required for this anti-proliferative activity. In stark contrast to cisplatin, VR54 neither activates the DNA-damage response network nor induces significant levels of cell death. Instead, VR54 is cytostatic and inhibits cell proliferation by up-regulating the cyclin-dependent kinase inhibitor p27KIP1 and inhibiting retinoblastoma protein phosphorylation, which blocks entry into S phase and results in G1 cell cycle arrest. Thus, VR54 inhibits cancer cell growth by a gain of function at the G1 restriction point. This is the first metal-coordination compound to demonstrate such activity. Arrested development: A binuclear ruthenium(II)-platinum(II) terpyridyl complex, VR54 (see structure), inhibits cancer cell proliferation. In contrast to the vast majority of metal anticancer agents, VR54 is cytostatic and acts by up-regulating p27KIP1, inhibiting retinoblastoma protein (Rb) phosphorylation and inducing G1 cell cycle arrest.

The interaction with duplex DNA of a series of 12 previously synthesised ruthenium (II) complexes incorporating extended terpyridines or analogous ligands is reported. The interaction was investigated using absorption spectroscopy and also, when possible, luminescence spectroscopy. Binding parameters for the interactions were estimated using established models. It was found that binding affinities are relatively large and their magnitude is somewhat dependent on the metal centre attached to the ligand. Viscosity studies reveal that all the complexes interact with DNA through groove binding and not intercalation. The variation in binding affinities of these complexes is rationalised by a consideration of electrostatic and steric factors.

The DNA duplex binding properties of previously reported dinuclear Ru(II) complexes based on the ditopic ligands tetrapyrido[3,2-a:2',3'-c:3'',2''-h:2'',3''-j]phenazine (tppz) and tetraazatetrapyrido[3,2-a:2'3'-c:3'',2''-l:2''',3'''-n]pentacene (tatpp) are reported. Photophysical and biophysical studies indicate that, even at high ionic strengths, these complexes bind to duplex DNA, through intercalation, with affinities that are higher than any other monointercalating complex and are only equalled by DNA-threaded bisintercalating complexes. Additional studies at high ionic strengths using the 22-mer d(AG(3)[T(2)AG(3)](3)) [G3] human telomeric sequence reveal that the dinuclear tppz-based systems also bind with high affinity to quadruplex DNA. Furthermore, for these complexes, quadruplex binding is accompanied by a distinctive blue-shifted "light-switch" effect, characterized by higher emission enhancements than those observed in the analogous duplex effect. Calorimetry studies reveal that the thermodynamics of duplex and quadruplex binding is distinctly different, with the former being entirely entropically driven and the latter being both enthalpically and entropically favored.

An investigation into the potential of a series of Ruthenium (II) thiacrown complexes with general formula [Ru([9]aneS 3 )Cl 2 (L)] and [Ru([ n ]aneS 4 )Cl(L)] + , where L = DMSO or Ph 3 P, n = 12, 14, or 16, as hydrogen transfer reduction catalysts is reported. As part of these studies two new complexes incorporating [Ru([12]aneS 4 )] and [Ru([16]aneS 4 )] metal centres have been synthesised and fully characterised. The X-ray structure of one of these complexes is also reported. The UV/Vis spectra of these complexes are dominated by π → π* transitions, with weaker d → d transitions also being apparent. Using these eight structurally related complexes, studies on the transfer hydrogenation of acetophenone using propan-2-ol as the hydride source were carried out. This work revealed that the complexes displayed catalytic activity in the presence of a base promoter. Although the activity of these complexes were considerably lower than that of structurally related mixed-donor ligand systems, there was some evidence that the flexibility of the ligand did have an effect on initial catalytic activity.

The synthesis of a series of Ru" complexes incorporating thiacrown ligands ([12]ane-S 4 , [14]ane-S 4 , [16]ane-S 4 ), as well as 2,2'-bipyridine (bpy) or pyridine, is reported. Structural studies on these complexes have been carried out using a variety of techniques. Detailed 1 H NMR spectroscopic studies on the previously reported [Ru([12]ane-S4)(bpy)] 2 + (1) reveal that-contrary to earlier reports-the observed fluxional 1 H NMR behavior is not due to chemical exchange involving cleavage of the bpy Ru-N bond but is, in fact, due to lone-pair inversion of coordinated macrocyclic sulfur donor atoms. This phenomenon is also observed for the [14]ane-S 4 and [16]ane-S 4 analogues of 1. For the first time, using a combination of X-ray crystallography, more detailed 'H NMR experiments, and computational methods, an in-depth study on the energetics and dynamics of invertomer formation and conversion for macrocyclic coordination complexes has been carried out. These studies reveal that the steric constraints of assembling each sulfur macrocycle and bpy ligand around the octahedral Ru I I center lead to close intramolecular contacts. These contacts are largely dependent on the orientation of the electron lone pairs of equatorial sulfur donor atoms and correlate with the comparative stability of the different invertomeric forms. Thus, the conformational preferences of the three macrocyles in [Ru([n]ane-S 4 )(bpy)] 2 + complexes are determined by steric rather than electronic effects.

The reaction of the extended terpyridyl ligands, 4′-(4′′′-pyridyl)-2, 2′:6′,2″-terpyridine (qtpy), and 4′-phenyl-2,2′:6′,2′′-terpyridine (ptpy) with RhCl3 and [tpyRhCl3] (where tpy=2,2′:6′,2′′-terpyridine) has been investigated. This has led to the isolation and characterisation of four new complexes. All the new complexes have had their molecular structures confirmed via X-ray crystallography studies. It has been shown that, consistent with related systems, changes in the electronic properties of the coordinated ligand results in modulation of the electrochemical and photophysical properties of the complex to which it is coordinated.

In vitro characterization and comparison of JDTic, its dehydroxy analogue and nor-BNI, and its dehydroxy analogue demonstrates that the N-substituted 3,4-dimethyl-(3-hydroxyphenyl)piperidine-derived antagonist, JDTic, relies more heavily on its phenol address group for affinity and antagonist activity relative to the corresponding naltrexone derived antagonists, nor-BNI. The structural flexibility of the former class of compound relative to the latter is postulated to underlie the difference.

A library of compounds biased toward opioid receptor antagonist activity was prepared by incorporating N-phenylpropyl-4beta-methyl-5-(3-hydroxyphenyl)morphans as the core scaffold using simultaneous solution phase synthetic methodology. From this library, N-phenylpropyl-4beta-methyl-5-(3-hydroxyphenyl)-7alpha-[3-(1-piperidinyl)propanamido]morphan [(-)-3b] was identified as the first potent and selective kappa opioid receptor antagonist from the 5-phenylmorphan class of opioids.

The synthesis and properties of 3 new ligand-bridged bimetallic complexes, 1(2+), 2(2+), and 3(2+), containing [RuCl([9]aneS(3))](+) metal centers are reported. Each complex was bridged by a different ditopic ligand. 1(2+) is bridged by 3,6-bis(2-pyridyl)-1,2,4,5-tetrazine (bptz), while 2(2+) and 3(2+) are bridged by 2,3-bis(2-pyridyl)pyrazine (dpp) and 2,2'-bipyrimidine (bpym), respectively. The Ru([II]) isovalent states of these complexes have been investigated using a variety of techniques. In the case of 3(2+), X-ray crystallography studies show preferential crystallization of an anti form with respect to coordinated chloride ligands (crystal data for [3][Cl(2)].4H(2)O: C(20)H(38)Cl(4)N(4)O(4)Ru(2)S(6), monoclinic, space group P2(1)/a, a = 10.929(14), b = 13.514(17), c = 11.299(16) A, beta = 90.52(1), V = 1669 A(3), Z = 2). UV/vis spectroscopy shows that spectra of these complexes are dominated by intraligand (pi--pi) and metal-to-ligand Ru(d)--L(pi) charge transfer transitions. Electrochemical studies reveal that metal-metal interactions are sufficiently intense to generate the Ru(III)/Ru(II) mixed valence [[RuCl([9]aneS(3))(2)](L-L)](3+) state, where L-L = individual bridging ligands. Although the 1(3+), 2(3+), and 3(3+) mixed valence states were EPR silent at room temperature and 77 K, isotropic solution spectra were observed for the electrochemically generated radical cations 1(+), 2(+), and 3(+), with 1(+) displaying well-resolved hyperfine coupling to bridging ligand nitrogens. Using UV/vis/NIR spectroelectrochemistry, we investigated optical properties of the mixed valence complexes. All three showed intervalence charge transfer (IVCT) bands that are much more intense than electrochemical data indicate. Indeed, a comparison of IVCT data for 1(3+) with an analogous structure containing [(NH3)(3)Ru](2+) metal centers shows that the IVCT in the new complex is an order of magnitude more intense. It is concluded that although the new complexes show relatively weak electrostatic interactions, they possess large resonance energies.

The synthesis of two new luminescent dinuclear Ir(III)-Ru(II) complexes containing tetrapyrido[3,2-a:2',3'-c:3'',2''-h:2''',3'''-j]phenazine (tpphz) as the bridging ligand is reported. Unlike many other complexes incorporating cyclometalated Ir(III) moieties, these complexes display good water solubility, allowing the first cell-based study on Ir(III)-Ru(II) bioprobes to be carried out. Photophysical studies indicate that emission from each complex is from a Ru(II) excited state and both complexes display significant in vitro DNA-binding affinities. Cellular studies show that each complex is rapidly internalised by HeLa cells, in which they function as luminescent nuclear DNA-imaging agents for confocal microscopy. Furthermore, the uptake and nuclear targeting properties of the complex incorporating cyclometalating 2-(4-fluorophenyl)pyridine ligands around its Ir(III) centre is enhanced in comparison to the non-fluorinated analogue, indicating that fluorination may provide a route to promote cell uptake of transition-metal bioprobes.

The duplex-DNA binding properties of a nonintercalating polypyridyl ruthenium(II) complex that incorporates a linear extended ligand with a catechol moiety has been probed with a variety of photo- and biophysical techniques. These studies reveal that the complex groove binds to DNA sequences biphasically, and displays binding constants equivalent to those of high-affinity metallointercalators. The complex also displays preferential binding to AT-rich sequences. Changes in the structure of the coordinated catechol ligand and the incorporation of intercalating ancillary ligands into the complex were found to modulate both the optical-binding response and binding parameters of the system, which indicates that the catechol moiety plays a crucial role in the observed enhancement to binding affinities.

The interaction of luminescent dinuclear ruthenium(II) complexes containing the bridging ligand tetrapyrido[3,2-a:2′,3′-c:3′′,2′′-h:2′′,3′′-j]phenazine with several intramolecular and intermolecular quadruplex DNA structures has been explored. It was found that these interactions produced distinctly different luminescence signatures. Binding curves constructed from these optical changes reveal that binding affinities for the quadruplex structures vary by over two orders of magnitude. The differences in quadruplex binding affinity and optical signature are rationalized through a consideration of the structural features of the quadruplexes. In particular we conclude large blue shifted emission enhancements are only observed on binding to quadruplexes containing lateral loops that are at least three base pairs long.

The single crystal X-ray structure of the newly synthesized ruthenium (II)-polypyridyl complex, [(bpy)(2)Ru(L)](PF(6))(2) (1) (bpy is 2,2'-bipyridyl and L is 2-methyl-2H-1,3,7,8-tetraaza-cyclopenta[l]phenanthren-2-ol revealed a near planar conformation for the fused imidazole moiety, suggesting the complex may be capable of binding to duplex DNA. Binding-induced changes in spectral properties, along with thermal denaturation and viscosity measurement studies confirmed that the complex binds to CT-DNA with a moderately high binding constant value (4.1 x 10(5) M(-1)) through intercalation. Photocleavage studies with the pBR322 plasmid DNA were performed following excitation of this complex into the Ru(dpi) --bpy/L(pi*)-based MLCT band and have shown that this complex cleaves the circular pBR322 DNA into linear DNA. Inhibitor studies revealed that the hydroxyl radicals were mainly responsible for the DNA photocleavage reaction. Preliminary studies indicate that the -OH functionality in 1 was also found to hydrolyse the phosphodiester linkage of pBR322 in the dark.

We report the synthesis of three new complexes related to the achiral [Ru(tpm)(dppz)py](2+) cation (tpm=tripyridazole methane, dppz=dipyrido[3,2-a:2',3'-c]phenazine, py=pyridine) that contain an additional single functional group on the monodentate ancillary pyridyl ligand. Computational calculations indicate that the coordinated pyridyl rings are in a fixed orientation parallel to the dppz axis, and that the electrostatic properties of the complexes are very similar. DNA binding studies on the new complexes reveal that the nature and positioning of the functional group has a profound effect on the binding mode and affinity of these complexes. To explore the molecular and structural basis of these effects, circular dichroism and NMR studies on [Ru(tpm)(dppz)py]Cl(2) with the octanucleotides d(AGAGCTCT)(2) and d(CGAGCTCG)(2), were carried out. These studies demonstrate that the dppz ligand intercalates into the G(2)-A(3) step, with {Ru(tpm)py} in the minor groove. They also reveal that the complex intercalates into the binding site in two possible orientations with the pyridyl ligand of the major conformer making close contact with terminal base pairs. We conclude that substitution at the 2- or 3-position of the pyridine ring has little effect on binding, but that substitution at the 4-position drastically disrupts intercalative binding, particularly with a 4-amino substituent, because of steric and electronic interactions with the DNA. These results indicate that complexes derived from these systems have the potential to function as sequence-specific light-switch systems.

The synthesis of dinuclear [Ru(II)([n]aneS(4))] (where n = 12, 14) complexes of the bridging ligand 3,6-bis(2-pyridyl)-1,2,4,5-tetrazine are reported. The X-ray structures of both of the new complexes are compared to a newly obtained structure for a dinuclear [Ru(II)([9]aneS(3))]-based analogue, whose synthesis has previously been reported. A comparison of the electrochemistry of the three complexes reveals that the first oxidation of the [Ru(II)([n]aneS(4))]-based systems is a ligand-based couple, indicating that the formation of the radical anion form of the bridging ligand is stabilized by metal center coordination. Spectroelectrochemistry studies on the mixed-valence form of the new complexes suggest that they are Robin and Day Class II systems. The electrochemical and electronic properties of these complexes is rationalized by a consideration of the pi-bonding properties of thiacrown ligands.

Three new water-soluble dppz derivatives are reported, one of which binds to DNA with an affinity comparable to any mononuclear metal complex and also displays a high selectivity for GC sites.

An improved synthesis of a water-soluble derivative of dipyrido[3,2-a:2',3'-c]phenazine (dppz) is reported. The structures of both dppz and the cation ethylene-bipyridyldiylium-phenazine dinitrate [[1][(PF(6))(2)]] have been obtained via X-ray crystallography. Metal complex derivatives of dppz are very well studied. However, using the water soluble [1][(NO(3))(2)], the nature of the interaction of a simple dppz unit with duplex DNA has been investigated for the first time. In both organic solvents and water, 1 displays unstructured luminescence, assigned to an intramolecular charge transfer. The emission is quenched on binding to natural and synthetic duplex DNA, including poly(dA).poly(dT). A variety of techniques reveal that the cation binds to DNA with an affinity comparable to those of many metal dppz complexes, via an intercalative binding mode.

Using achiral coordinatively unsaturated metal complex building-blocks, the two step synthesis of a bimetallic complex containing independent [Ru(II)dppz] units tethered together by a linking 4,4'dipyridyl-1,5-pentane ligand is reported. Photophysical studies on this prototype system indicate that the characteristic luminescence of the [Ru(II)dppz] moieties is perturbed by self-quenching processes. Preliminary binding studies on the complex with natural and synthetic duplex DNA is reported. Luminescence and calorimetric titrations reveal that the complex does not show enhanced binding affinity with respect to analogous monometallic complexes. This result is interpreted by a consideration of the length and rigidity of the linker employed in the complex.

Hydrogen-bonded dimers of one and two base-pair nucleotides can be stabilized inside the hydrophobic pocket provided by self-assembled molecular cages. The results could bring DNA-based computing a step closer to reality.

The syntheses of two water soluble dipyrido-[3,2-a:2',3'-c]-phenazine analogues containing one or two appended amino/amide chains are reported. Steady state optical studies on the two new compounds reveal high-energy dppz-based luminescence in water and non-aqueous solvents. Optical titrations with duplex DNA show that the luminescence is quenched on the addition of DNA. Binding curves constructed from absorption and emission changes indicate that, while one of the compounds display negligible binding properties, the other binds DNA with relatively high affinity (10(5) M(-1)). Isothermal calorimetry experiments, designed to investigate the higher binding compound in more detail, reveals that its interaction with CT-DNA is actually biphasic with one tight (10(5) M(-1)) and one weaker binding site (~10(5) M(-1)). In both cases binding is entropically driven. Further calorimetry studies involving the interaction of the new compound with a variety of polynucleotides were carried out. To aid comparisons, similar experiments involving a previously reported bipyridyldiylium derivative of dppz were also carried out. These studies reveal that the bipyridyldiylium derivative binds all these sequences monophasically with relatively low affinities (~10(4) M(-1)). However, while the amino/amide chain appended derivative binds to Poly(dA).poly(dT) monophasically with relatively low affinities, it binds all the other polynucleotide studied biphasically, with affinities ranging from10(6) M(-1) to10(8) M(-1). The ITC data reveals that for both compounds thermodynamic signatures for binding are dependent on the sequence being bound. In both cases, the data for Poly(dA).poly(dT) is particularly anomalous. An analysis of the data shows that binding is selective, with affinities at flexible sequences being several orders of magnitude higher than those at more rigid sequences.

The cover picture shows the crystal structure of a heteronuclear trimetallic complex of a “back-to-back” ligand superimposed on a view of the wild heather near Kettlewell in the Yorkshire Dales national park, near Leeds. The ligand contains two different metal-binding domains that can be sequentially metallated with high selectivity – there is no detectable exchange of metal ions between the domains of the ligand in solution. The iron(II) ion at the centre of the complex undergoes a spin transition on cooling, in solution and in the solid state. Details are discussed in the Short Communication by M. A. Halcrow et al. on p. 1007 ff.

The title compound forms a novel hydrogen bond network combining helical and non-helical connectivity, comprised of alternate rows of coparallel left-handed and right-handed helices separated by additional 64-connected nodes.

An amide macrocycle with a highly preorganised cavity containing both polar and non-polar recognition sites forms stable complexes with cyclic dipeptides in water via amide–amide hydrogen-bonds, NH–π hydrogen-bonds and hydrophobic contacts.

In one step, 8 octahedral metal ‘corners’ and 12 ligand ‘edges’ come together to form a supramolecular cube.

The synthesis of the complex [RhCl3tpm*], 1, (tpm* = tris(3,5-dimethylpyrazolyl)methane) is reported. Complex 1 is a suitable starting material for the synthesis of heteroleptic half-sandwich complexes: it has been used to synthesise the complexes; [RhCl(bpy)tpm*][(PF6)2] [2][(PF6)2] (bpy = 2,2′-bipyridyl), [RhCl(phen)tpm*][(PF6)2] [3][(PF6)2]. (phen = 1,10-phenanthroline), [RhCl2(py)tpm*][(PF6)], [4][(PF6)2], (py = pyridine), and[RhCl(py)2tpm*][(PF6)2], [5][(PF6)2]. The structures of [2][(PF6)2], [3][(PF6)2], [4][(PF6)2], and [5][(PF6)2] have been determined by X-ray crystallography. The electrochemical and photophysical properties of these new compounds have also been investigated.

The monometallic bipyridyl complexes [MoTp*(NO)X(L-L)] [Tp* = HB(3,5-Me2C3HN2)3; L-L = 3,3‘-bipyridine, 4,4‘-bipyridine, 1,2-bis(4-pyridyl)ethane and X = Cl; L-L = 4,4‘-NC5H4(CHCH)nH4C5N, n = 0, 1, 2, 3, 4 (all trans) and X = Cl, I] and their bimetallic counterparts [{(NO)MoTp*X}2(L-L)] have been synthesized, together with [MoTp*(NO)Cl{4-NC5H4CHCHC(Me)CHCH}]2. The single crystal X-ray structure of [{MoTp*(NO)Cl}2{4,4‘-NC5H4(CHCH)4H4C5N}] confirms that the polyene chain is in the all-trans configuration and exhibits normal bond length alternation with [rCC−rCC] = 0.092 A. The Mo−Mo distance is 20.764(3) A, and the Mo−N(pyridyl) bond distance of 2.196(6) A indicates a much lower degree of Mo−(N)ligand π bonding than that found in related amide complexes where Mo−N(amide) distances are typically some 0.3 A shorter. Cyclic voltammograms of the monometallic complexes contain a single one-electron reduction process, whereas those of the bimetallic complexes contain two one-electron processes. The separation bet...