Dpb Ligand Research Articles

Photoactivated full-API nanodrug (FAND): harnessing transition metal complexes and MTH1 inhibitor for enhanced DNA damage in cancer cells.

The effectiveness of photodynamic therapy (PDT) has been greatly restricted by the hypoxic tumor microenvironment and the susceptible resistance of monotherapy. Although nanodrugs based on transition metal complexes capable of integrating PDT with photoactivated chemotherapy (PACT) have garnered tremendous attention as promising candidates for overcoming the above limitations, the therapeutic efficacy of these nanodrugs is still hampered by inadequate loading of active pharmaceutical ingredients (APIs) and the inherent ability of cancer cells to repair damaged DNA. Herein, we developed a photoactivated full-API nanodrug, Ru-T FAND, by one-step self-assembly of RuDPB and TH287. By virtue of its 100 wt% API content and favorable stability in water, the Ru-T FAND exhibited improved cellular uptake behavior and intracellular 1O2 generation. Attractively, the Ru-T FAND with triple anti-cancer modalities can photogenerate 1O2, photo-release DPB ligand and inhibit the repair of DNA damage, ultimately enhancing its phototherapeutic effect on cancer cells. Importantly, the uncaged DPB ligand from RuDPB emits red fluorescence, enabling real-time monitoring of the drug's absorption, distribution and efficacy. Collectively, the presented photoactivated Ru-T FANDs with multiple anti-cancer mechanisms will expand new horizons for the development of safe, efficient and synergistic tumor phototherapy strategies.

C–H Metalation of Terpyridine Stereoisomers with Ni(II), Pd(II), and Pt(II)

Ni(II), Pd(II), and Pt(II) complexes [M(Y-terpy)X] (X = Cl or Br) containing the tridentate N^C^N-cyclometalating 2,3′:5′,2″and 2,2′:4′,2″ stereoisomers of the well-known tridentate N^N^N ligand 2,2′:6′,2″-terpyridine (terpy) were synthesised in moderate to good yields through C–H activation. For the Pt complexes, the phenyl ethynide derivatives [Pt(Y-terpy)(C≡CPh)] were also obtained under Sonogashira conditions. In contrast to this, C^N^N cyclometalated complexes using the 2,2′:6′,3″- and 2,2′:6′4″-terpy isomers were not obtained. Comparison of the N^C^N complexes of the cyclometalated 2,3′:5′,2″- and 2,2′:4′,2″-terpy ligands with complexes [M(dpb)Cl] of the prototypical N^C^N cyclometalating ligand dpb− (Hdpb = 2,6-diphenyl-pyridine) showed higher potentials for the terpy complexes for the ligand-centred reductions in line with the superior π-accepting properties of the terpy ligands compared with dpb. Metal-centred oxidations were facilitated by the dpb ligand carrying a central σ-donating phenyl group instead of a metalated pyridine moiety. The same trends were found for the long-wavelength absorptions and the derived electrochemical and optical band gaps. The lower σ-donating capacities of the cyclometalated terpy derivatives is also confirmed by a reduced trans influence in the structure of [Ni(2,3′:5′,2″-terpy)Br0.14/OAc0.86]. Attempts to re-crystallise some poorly soluble Pd(II) and Pt(II) complexes of this series under solvothermal conditions (HOAc) gave two structures with N-protonated cyclometalated pyridine moieties, [Pt(2,3′:5′,2″-terpyH)Cl].Cl and [Pd(2,3′:5′,2″-terpyH)Cl2].

A 3D supramolecular assembly based on a {AsW12} cluster and in-situ ligand modified metal-organic complexes for photocatalytic properties and electrocatalytic sensing for detection of hydrogen peroxide

A Keggin-type arsenotungstate supramolecular assembly modified with metal-organic complexes, {Zn(dpb)2}2{AsWVI11WV O40}·4H2O (1) (dpb ​= ​2,6-di(2-pyridine)-4,4′-bipyridine), have been synthesized under hydrothermal condition and fully characterized by routine method. In compound 1, each {AsW12O40} cluster is attached to eight Zn(dpb)2 complexes, which are further attracted by four Keggin analogues, forming a tightly packed three-dimensional supramolecular network through strong H-bonds and π-π interactions. It is worth noting that the dpb ligand in the complex {Zn(dpb)2} is produced from the ptz and dpp precursor via under hydrothermal conditions for the first time and its possible assembly path is discussed. The stacking pattern of compound 1 can be simplified to 4,8-connected network with topology {410·610·88}{45·6}2. Compound 1 modified glassy carbon electrode (1-GCE) exhibits significant electrocatalytic reduction activity and outstanding sensing performance for H2O2 with low detection limit (0.43 ​μM) and wide linear range (1.28 μM-2.23 ​mM). Meanwhile, it has high efficiency photocatalytic degradation performance for refractory dyes under ultraviolet irradiation.

Inhibition of Matrix Metalloproteinases and Cancer Cell Detachment by Ru(II) Polypyridyl Complexes Containing 4,7-Diphenyl-1,10-phenanthroline Ligands-New Candidates for Antimetastatic Agents.

Primary tumor targeting is the dominant approach in drug development, while metastasis is the leading cause of cancer death. Therefore, in addition to the cytotoxic activity of a series of Ru(II) polypyridyl complexes of the type [Ru(dip)2L]2+ (dip: 4,7-diphenyl-1,10-phenanthroline while L = dip; bpy: 2,2′-bipyridine; bpy-SC: bipyridine derivative bearing a semicarbazone 2-formylopyridine moiety; dpq, dpq(CH3)2, dpb: quinoxaline derivatives) their ability to inhibit cell detachment was investigated. In vitro studies performed on lung cancer A549 cells showed that they accumulate in cells very well and exhibit moderate cytotoxicity with IC50 ranging from 4 to 13 µM. Three of the studied compounds that have dip, bpy-SC, or dpb ligands after treatment of the cells with a non-toxic dose (<1/2IC50) enhanced their adhesion properties demonstrated by lower detachment in the trypsin resistance assay. The same complexes inhibited both MMP-2 and MMP-9 enzyme activities with IC50 ranging from 2 to 12 µM; however, the MMP-9 inhibition was stronger. More detailed studies for [Ru(dip)2(bpy-SC)]2+, which induced the greatest increase in cell adhesion, revealed that it is predominately accumulated in the cytoskeletal fraction of A549 cells. Moreover, cells treated with this compound showed the localization of MMP-9 to a greater extent also in the cytoskeleton. Taken together, our results indicate the possibility of a reduction of metastatic cells escaping from the primary lesion to the surrounding tissue by prevention of their detachment and by influencing the activity of MMP-2 and MMP-9.

Construction of Uranyl Organic Hybrids by Phosphonate and in Situ Generated Carboxyphosphonate Ligands.

The hydrothermal reaction of uranyl ions with (5-methyl-1,3-phenylene)diphosphonic acid (H4MPDP) in the presence of additives such as nitric acid, N-bearing species, and heterometal ions yielded five new uranyl organic hybrids: (H3O)[(UO2)5(H2O)4(H3DPB)2(H2DPB)(HDPB)]·2H2O (1), (Hphen)(phen)[(UO2)3(H2DPB)(HDPB)] (2), (H2dipy)[(UO2)3(MPDP)2] (3), Zn(bipy)(UO2)(MPDP) (4), and Co(bipy)(UO2)(MPDP)·H2O (5) (H5DPB = 3,5-diphosphonobenzoic acid; phen = 1,10-phenanthroline; dipy = 4,4'-bipyridine; bipy = 2,2'-bipyridine). Single-crystal X-ray diffraction (XRD) demonstrates that 1 and 2 are 3D frameworks constructed of uranyl centers and carboxyphosphonate DPB ligands; the latter were formed via the in situ oxidation of H4MPDP. In the homometallic uranyl diphosphonate 3, less common UO6 square bipyramids connected by MPDP ligands were incorporated to form the 2D assembly. A further introduction of heterometal ions produced two heterobimetallic uranyl phosphonates 4 and 5. Both of them show layered structures, formed by UO6 square bipyramids linked by MPDP ligands with heterometal-centered polyhedra decorated on the sides of the layers. It is found that the pH and heterometal ions have significant effects on the structures of the complexes. In addition to the syntheses and XRD characterization, the spectroscopic properties of these uranyl complexes were also addressed. To complement the experimental results, density functional theory calculations were carried out on several model complexes that feature a homo- or heterobimetallic molecular skeleton. Geometrical/electronic structures, IR spectra, and electronic absorptions were discussed.

Steric and Electronic Factors Associated with the Photoinduced Ligand Exchange of Bidentate Ligands Coordinated to Ru(II).

In an effort to create a molecule that can absorb low energy visible or near-infrared light for photochemotherapy (PCT), the new complexes [Ru(biq)2 (dpb)](PF6 )2 (1, biq = 2,2'-biquinoline, dpb = 2,3-bis(2-pyridyl)benzoquinoxaline) and [(biq)2 Ru(dpb)Re(CO)3 Cl](PF6 )2 (2) were synthesized and characterized. Complexes 1 and 2 were compared to [Ru(bpy)2 (dpb)](PF6 )2 (3, bpy = 2,2'-bipyridine) and [Ru(biq)2 (phen)](PF6 )2 (4, phen = 1,10-phenanthroline). Distortions around the metal and biq ligands were used to explain the exchange of one biq ligand in 4 upon irradiation. Complex 1, however, undergoes photoinduced dissociation of the dpb ligand rather than biq under analogous experimental conditions. Complex 3 is not photoactive, providing evidence that the biq ligands are crucial for ligand photodissociation in 1. The crystal structures of 1 and 4 are compared to explain the difference in photochemistry between the complexes. Complex 2 absorbs lower energy light than 1, but is photochemically inert although its crystal structure displays significant distortions. These results indicate that both the excited state electronic structure and steric bulk play key roles in bidentate photoinduced ligand dissociation. The present work also shows that it is possible to stabilize sterically hindered Ru(II) complexes by the addition of another metal, a property that may be useful for other applications.

Luminescence color tuning of Pt(II) complexes and a kinetic study of trimer formation in the photoexcited state.

We investigated the luminescence properties and color tuning of [Pt(dpb)Cl] (dpbH=1,3-di(2-pyridyl)benzene) and its analogues. An almost blue emission was obtained for the complex [Pt(Fmdpb)CN] (FmdpbH=4-fluoro-1,3-di(4-methyl-2-pyridyl)benzene), modified by the introduction of F and CH3 groups to the dpb ligand and the substitution of Cl by CN. As the concentration of the solution was increased, the color of the emission varied from blue to white to orange. The color change resulted from a monomer-excimer equilibrium in the excited state. A broad emission spectrum around 620 nm was clearly detected along with a structured monomer emission around 500 nm. Upon further increases in concentration, another broad peak appeared in the longer wavelength region of the spectrum. We assigned the near-infrared band to the emission from an excited trimer generated by the reaction of the excimer with the ground-state monomer. The emission lifetimes of the monomer, dimer, and trimer were evaluated as τM =12.8 μs, τD =2.13 μs, and τT =0.68 μs, respectively, which were sufficiently long to allow association with another Pt(II) complex and dissociation into a lower order aggregate. Based on equilibrium constants determined from a kinetic study, the formation of the excimer and the excited trimer were concluded to be exothermic processes, with ΔG*D =-24.5 kJ mol(-1) and ΔG*T =-20.4 kJ mol(-1) respectively, at 300 K.

Cadmium–Organic Coordination Polymers Based on N-Donor Ligands and Small Anions: Syntheses, Crystal Structures, and Photoluminescent Properties

By using two types of arene core-based rigid N-containing ligands, we have solvothermally synthesized two cadmium metal–organic coordination polymers, {[Cd6(dpb)6(HCOO)8(H2O)4]·4NO3·4H2O}n (1) and {[Cd4(tib)4(H2O)4(NO3)6]·2NO3}n (2) (dpb = 1,4-bis-(4-pyridyl)-benzene, tib = 1,3,5-tris(1-imidazolyl)benzene), and characterized them. The coordinated small anions HCOO– and NO3– play important roles in the formation of 1 and 2. In 1, the coordinated formate ligand from in situ hydrolysis of DMF binds metal centers to generate a rigid 2D metal–formate honeycomb layer, which is further connected by dpb ligands to generate a 3D pillar–layer complex. Complex 2 possesses a 2-fold interpenetrating 2D framework with an extremely rare (3,4) connected topology. Photochemical properties of these new complexes have been studied.

Ru(bpy)3−n(dpb)n]2+: Unusual Photophysical Property and Efficient DNA Photocleavage Activity

The sequential replacement of a bpy ligand (bpy = 2,2'-bipyridine) by a dpb ligand (dpb = 2,3-bis(2-pyridyl) benzoquinoxaline) in the series [Ru(bpy)(3-n)(dpb)(n)](2+) (n = 1-3) leads to a remarkable increase of the excited state lifetime, the (1)O(2) quantum yield, and the binding affinity toward dsDNA, rendering both [Ru(bpy)(dpb)(2)](2+) and [Ru(dpb)(3)](2+) efficient DNA photocleavage activities upon red light irradiation (>or=600 nm).

A New Heteroleptic Ruthenium(II) Polypyridyl Complex with Long‐Wavelength Absorption and High Singlet‐Oxygen Quantum Yield

Ruthenium(II) polypyridyl complexes with long-wavelength absorption and high singlet-oxygen quantum yield exhibit attractive potential in photodynamic therapy. A new heteroleptic Ru(II) polypyridyl complex, [Ru(bpy)(dpb)(dppn)](2+) (bpy=2,2'-bipyridine, dpb=2,3-bis(2-pyridyl)benzoquinoxaline, dppn=4,5,9,16-tetraaza-dibenzo[a,c]naphthacene), is reported, which exhibits a (1)MLCT (MLCT: metal-to-ligand charge transfer) maximum as long as 548 nm and a singlet-oxygen quantum yield as high as 0.43. Steady/transient absorption/emission spectra indicate that the lowest-energy MLCT state localizes on the dpb ligand, whereas the high singlet-oxygen quantum yield results from the relatively long (3)MLCT(Ru-->dpb) lifetime, which in turn is the result of the equilibrium between nearly isoenergetic excited states of (3)MLCT(Ru-->dpb) and (3)pipi*(dppn). The dppn ligand also ensures a high binding affinity of the complex towards DNA. Thus, the combination of dpb and dppn gives the complex promising photodynamic activity, fully demonstrating the modularity and versatility of heteroleptic Ru(II) complexes. In contrast, [Ru(bpy)(2)(dpb)](2+) shows a long-wavelength (1)MLCT maximum (551 nm) but a very low singlet-oxygen quantum yield (0.22), and [Ru(bpy)(2)(dppn)](2+) shows a high singlet-oxygen quantum yield (0.79) but a very short wavelength (1)MLCT maximum (442 nm).

Synthesis and Crystal Structure of the Dicopper(II) Complex [Cu2{Ph2P(=O)(o-C6H4)CO2}2(THF)2(H2O)2][BF4]2by Oxidation of [Cu{Ph2P(o-C6H4)C(=O)H}2(NCMe)][BF4] with Aqueous H2O2

Treatment of [Cu(pcho)2(NCMe)][BF4] 1 (pcho = 2-(diphenylphosphino)benzaldehyde) with aqueous H 2 O 2 in THF solvent affords [Cu 2 (dpb) 2 (THF) 2 (H 2 O) 2 ] [BF 4 ] 2 2 (dpb = 2-(diphenylphosphinoxide)-benzoate) after crystallization from diethyl ether. This reaction involves oxidation of Cu(I) to Cu(II) ion, phosphine to phosphinoxide, and benzaldehyde to benzoate species. The crystal structure of 2 consists of two copper(II) atoms bridged by two carboxylate moieties of the dpb ligands. The coordination about each copper(II) atom is a distorted trigonal bipyramid.

The 1,4-diphosphabuta-1,3-diene ligand for coordination of divalent group 13 and 14 elements: a density functional study.

The 1,4-diphosphabuta-1,3-diene (DPB) ligand as a tool for stabilizing anionic group 13 (B, Al, Ga) and neutral group 14 (C, Si, Ge) cyclic Arduengo-type carbenes is studied by quantum chemical calculations at density functional level. Accordingly, for the former group this ligand is better suited than the corresponding 1,4-diazabuta-1,3-diene (DAB) ligand. It results in larger electron affinities for the corresponding doublet states. For the latter group the DPB ligand yields essentially smaller singlet-triplet separations than the DAB ligand. An exception is the anionic boron compound with relative low singlet stability for both the DAB and DPB ligands.

Remarkably stable radical anions derived from clusters [HOs 3(CO) 9(L)], L= ortho-metallated α-diimine: a spectro-electrochemical study and theoretical rationalization

Reduction of the cluster [Os 3(CO) 10( i Pr-PyCa)], i Pr–PyCa= σ- N, σ- N′-pyridine-2-carbaldehyde- N-isopropyl-imine, ( 1) follows an ECEC sequence. The initial one-electron reduction step produces the radical anion 1 − which was found stable on a subsecond time scale at low temperatures. At room temperature an open-structure radical anionic transient 1a − is formed which instantaneously reduces to 1a 2−. Subsequent attack of the latter species at yet nonreduced 1 yields an Os–Os bonded cluster dimer [ 1a– 1a] 2−. In contrast to the reactivity of 1 − , the radical anions of the clusters [HOs 3(CO) 9(C 5H 3N-2-C(H)N– i Pr)] ( 2), [HOs 3(CO) 9(6-CH 2–C 5H 3N-2-C(H)N– i Pr)] ( 3), containing the ortho-metallated ligands o- i Pr–PyCa{6-X} (X=H, Me}, are substantially more stable. At room temperature in THF, 2 − and 3 − slowly disproportionate to moderately stable dianionic species 2b and 3c. IR and 1H-NMR spectra of 2b have revealed the presence of bridging CO and terminal hydride ligands, and the dominant localization of the negative charge on the metallic core. The structure of 3c is probably similar. The latter dianions were also obtained by direct one-electron reduction of 2 − and 3 − , respectively. Both radical anions are inherently stable at T=253 K. According to extended Hückel molecular orbital calculations on models of the parent clusters 1– 3, the higher stability of 2 − and 3 − relative to that of 1 − has its origin in larger localization of the odd electron at the lowest π*-orbital of the ortho-metallated ligands compared to the σN, σN′-chelated i Pr–PyCa ligand, and in higher cluster-diimine binding energies of 2 and 3 which drop due the one-electron reduction less than calculated for the couple 1/ 1 − . IR and 1H-NMR spectra have revealed that 2,3-dipyrid-2′-ylbenzoquinoxaline (dpb) coordinates to the Os 3 core as an ortho-metallated ligand, forming [HOs 3(CO) 9(dpb-14-yl)] ( 4), in contrast to shorter 2,3-dipyrid-2′-ylpyrazine (dpp). The corresponding radical anion 4 − is inherently stable already at room temperature, mainly due to the large π-acceptor capacity of the ortho-metallated dpb ligand.

Interaction of methylmercury(II) with the bifunctional ligand o-diphenylphosphinobenzoate, dpb. Synthesis and characterization of [(dpb)HgMe] and [(dpbo)HgMe], dpbo= o-diphenylphosphinoxidebenzoate

The complex [(dpb)HgMe] ( 1) is obtained by reaction of MeHg(OH) with o-diphenylphosphinobenzoic acid (Hdpb); alternatively the solvate [(dpb)HgMe] · 0.5H 2O · 0.5C 5H 5N ( 1bis) can be prepared by reacting MeHgCl with Hdpb and pyridine. The derivative [(dpbo)HgMe] ( 2), where dpbo is o-diphenylphosphinoxidebenzoate, is formed by reaction of 1 or 1bis solutions with atmospheric oxygen. Crystal data for 1bis: monoclinic, space group P2/ n, a=10.413(4), b=9.831(3), c=20.674(3) Å, β=102.51(3)°, Z=2. Crystal data for 2: triclinic, space group P1̄, a=11.535(2), b=12.897(5), c=13.275(7) Å, α=88.31(4), β=73.65(4), γ=85.27(4)°, Z=2. In 1bis the mercury atom displays a distorted linear fashion, being coordinated to a methyl group and to the phosphorus atom of the dpb ligand. Two additional weaker linkages cause the packing in pairs of the molecules. In 2 the mercury is linearly linked to a methyl group and to an oxygen atom of the carboxylic group of the dpbo ligand. Also in this case the coordination around the mercury center is completed by two weaker additional bond interactions, which, involving the oxygen atoms of the adiacent moiety, determine the dimerization of the molecule. The multinuclear magnetic resonance spectra of 1 (or 1bis) which have been compared with those of the related complex [(PPh 3)HgMe](CF 3SO 3) ( 3) and of the solution containing 1 and CF 3SO 3H (molar ratio 1:1.5), do not seem to unambigously support a dimeric configuration of the complex in solution.

Dipalladium complexes with N,N'-diphenylbenzamidine bridging and chelating ligands. Synthesis and structural and electrochemical studies

The reaction of the palladium acetate trimer, Pd/sub 3/(OOCCH/sub 3/)/sub 6/, with lithium N,N/prime/-diphenylbenzamidinate, Li(dpb), in CH/sub 2/Cl/sub 2/ gives a product with molecular formula Pd/sub 2/(dpb)/sub 4/. A single-crystal x-ray structure analysis shows the complex to contain two palladium(II) ions bridged by two dpb ligands, with an additional dpb ion chelated to each of the metals forming four-membered rings, ((dpb)Pd)/sub 2/(/mu/-dpb)/sub 2/ (1). The crystal and molecular structure of 1 is reported. When 1 is refluxed in methanol, the two chelating ligands rearrange to form the tetrabridged complex, Pd/sub 2/(/mu/-dpb)/sub 4/ (2) and the crystal structure of this compound is reported. The oxidation potentials of 1 and 2 show an effect on the HOMO's of the two molecules due to the proximity of the two palladium ions. Both of the two noninteracting palladium ions of 1 are oxidized irreversibly at 1.02 V vs SCE in CH/sub 2/Cl/sub 2/, 0.1 M TBAP, whereas under the same conditions 2 undergoes a reversible one-electron oxidation at 0.65 V to form the cation-radical complex (Pd/sup II/Pd/sup III/(/mu/-dpb)/sub 4/)/sup +/. No other reversible cyclic wave was observed up to the potential limit of the solvent. The ESR spectrum of (Pd/sup II/Pd/sup III/(/mu/-dpb)/sub 4/)/sup +/more » clearly shows an axial signal with g/sub /perpendicular// = 2.17 and g/sub /parallel// = 1.98. Satellite peaks due to /sup 105/Pd (I = /5/2/, natural abundance 22.3%) are observed. The ESR spectrum is similar to that of the isoelectronic (Rh/sup I/Rh/sup II/(/mu/-dpb)/sub 4/)/sup /minus// complex and shows that the oxidation is metal centered. 20 refs., 5 figs., 4 tabs.« less