Fluorogenic Squaraine Dendrimers for Background-Free Imaging of Integrin Receptors in Cancer Cells

To overcome the limited brightness of existing fluorogenic molecular probes for biomolecular targets, we introduce a concept of fluorogenic dendrimer probe, which undergoes polarity-dependent switching due to intramolecular aggregation-caused quenching of its fluorophores. Based on a rational design of dendrimers with four and eight squaraine dyes, we found that octamer bearing dyes through a sufficiently long PEG(8) linker displays >400-fold fluorescence enhancement from water to non-polar dioxane. High extinction coefficient (≈2,300,000 m ⁻¹ cm⁻¹) resulted from eight squaraine dyes and quantum yield (≈25 %) make this octamer the brightest environment-sensitive fluorogenic molecule reported to date. Its conjugate with cyclic RGD used at low concentration (3 nm ) enables integrin-specific fluorescence imaging of cancer cells with high signal-to-background ratio. The developed dendrimer probe is a “golden middle” between molecular probes and nanoparticles, combining small size, turn-on response and high brightness, important for bioimaging.     

Efficient and simple colorimetric fluoride ion sensor based on receptors having urea and thiourea binding sites

[structure: see text] Novel colorimetric receptors for selective fluoride ion sensing containing anthraquinone as chromogenic signaling subunit and urea (N,N' '-(9,10-dihydro-9,10-dioxo-1,2-anthracenediyl)bis[N'-phenyl])/thiourea (N,N' '-(9,10-dihydro-9,10-dihydro-9,10-dioxo-1,2-antrhacenediyl)bis[N-phenyl]) binding sites have been reported. These receptors have shown no affinity for other halide ions (Cl-, Br-, and I- ions). Well-defined color change in the visible region of the spectrum was observed upon addition of fluoride ion in DMSO/CH3CN solution of the receptors 1 and 2.     

Visualization of nitroxyl in living cells by a chelated copper(II) coumarin complex

The coumarin-based probe Cu(II)-COT1 was successfully developed for the detection of HNO on the basis of the reduction reaction. In addition, highly selective "turn on" type fluorogenic behavior upon the addition of Angeli's salt (Na(2)N(2)O(3)) was also applied to bioimaging in A375 cells.     

Regioselective hydroxylation of the xylyl linker in a diiron(III) complex having a carboxylate-rich ligand with H2O2

Reaction of a diiron(III) complex having a xylta4- ligand (N,N,N',N'-m-xylylenediamine tetraacetate) with H2O2 resulted in regioselective hydroxylation of the m-xylyl linker. The reaction mimics the self-hydroxylation of a phenylalanine side chain found for ribonucleotide reductase (R2-W48F/D84E).     

Synthesis of a Far‐Red Photoactivatable Silicon‐Containing Rhodamine for Super‐Resolution Microscopy

The rhodamine system is a flexible framework for building small‐molecule fluorescent probes. Changing N‐substitution patterns and replacing the xanthene oxygen with a dimethylsilicon moiety can shift the absorption and fluorescence emission maxima of rhodamine dyes to longer wavelengths. Acylation of the rhodamine nitrogen atoms forces the molecule to adopt a nonfluorescent lactone form, providing a convenient method to make fluorogenic compounds. Herein, we take advantage of all of these structural manipulations and describe a novel photoactivatable fluorophore based on a Si‐containing analogue of Q‐rhodamine. This probe is the first example of a “caged” Si‐rhodamine, exhibits higher photon counts compared to established localization microscopy dyes, and is sufficiently red‐shifted to allow multicolor imaging. The dye is a useful label for super‐resolution imaging and constitutes a new scaffold for far‐red fluorogenic molecules.     

Metallkomplexe von Farbstoffen. X. Neue Übergangsmetallkomplexe von Anthrachinonfarbstoffen

Metal Complexes of Dyes. X. New Transition Metal Complexes of Anthraquinone Dyes The chloro-bridged compounds [(R₃P)MCl₂]₂ (M ? Pd, Pt; R ? ethyl, phenyl, n-butyl), [(Ph₃P)₂PdCl]₂(BF₄)₂, [(η⁵-C₅Me₅)MCl₂]₂ (M ? Rh, Ir), [(η⁶-p-cymene)RuCl₂]₂, react with mono- and dianions of several 9,10-anthracene-dione dyes [1-amino-9,10-anthracene-dione, Disperse Blue 19 (1-amino-4-anline-9,10-anthracene-dione), 1,4-diamino-9,10-anthracene-dione, Solventgreen 3 [1,4-bis(4′-methylaniline)-9,10-anthracene-dione], dianthrimide [1,1′-dianthraquinonylamin], 1-azo-β-naphtol-9,10-anthracene-dione, 1-anilido-o-carboxy-9,10-anthracene-dione and Quinizarin (1,4-dihydroxy-9,10-anthracene-dione)] to give N,O-, O,O- and O,N,O-chelate complexes. Copper(II)- and palladium(II) acetate and the anion of 1-aminoanthraquinone afford N,O-bischelates. Spectroscopic data are discussed. In comparision to the free anthraquinones the dye complexes show a bathochromic shift in the UV/VIS spectra. The structures of (ethyl)₃P(Cl)Pt(1-aminoanthraquinone-H⁺), (η-C₅Me₅)(Cl)Ir(1-azo-β- #naphtolanthraquinone-H⁺) and (η-C₅Me₅)Rh(1-anilido-o-carboxyanthraquinone-2 H⁺) were determined by X-ray diffraction.     

Chromogenic and fluorescent ‘‘turn-on' chemodosimeter for fluoride based on F~–-sensitive self-immolative linker

A new chromogenic and fluorescent ‘‘turn-on" chemodosimeter 3 was designed and synthesized by using a fluoride-sensitive self-immolative linker, in combination with the fluorescent dyes 7-hydroxy-4-trifluoromethyl coumarin. The chemodosimeter exhibited high selectivity and sensitivity toward fluoride anions through ‘‘turn-on" chromogenic and fluorogenic dual modes.     

A kinetics and mechanistic study on the role of the structural rigidity of the linker on the substitution reactions of chelated dinuclear Pt(II) complexes

Substitution reactions of platinum complexes bearing cyclohexylamine/diamine moieties viz., [Pt(H(2)O)(N,N-bis(2-pyridylmethyl)cyclohexylamine)](CF(3)SO(3))(2), bpcHna; [{Pt(H(2)O)}(2)(N,N,N',N'-tetrakis(2-pyridylmethyl)-trans-1,4-cyclohexyldiamine)](CF(3)SO(3))(4), cHn and [{Pt(H(2)O)}(2)(N,N,N',N'-tetrakis(2-pyridylmethyl)-4,4'-dicyclohexylmethanediamine)](CF(3)SO(3))(4), dcHnm and phenylamine/diamine moieties viz., ([Pt(H(2)O)N,N-bis(2-pyridylmethyl)phenylamine)](CF(3)SO(3))(2), bpPha; [{Pt(H(2)O)}(2)(N,N,N',N'-tetrakis(2-pyridylmethyl)-1,3-phenyldiamine)](CF(3)SO(3))(4), mPh; [{Pt(H(2)O)}(2)(N,N,N',N'-tetrakis(2-pyridylmethyl)-1,4-phenyldiamine)](CF(3)SO(3))(4), pPh and [{Pt(H(2)O)}(2)(N,N,N',N'-tetrakis(2-pyridylmethyl)-4,4'-diphenylmethanediamine)](CF(3)SO(3))(4)), dPhm with thiourea nucleophiles were studied in acidified 0.01 M LiCF(3)SO(3) aqueous medium under pseudo-first-order conditions using stopped-flow and UV-visible spectrophotometric techniques. The rate of substitution follows a similar trend in the two sets of complexes and decreases in the order: bpcHna > dcHnm > cHn and bpPha > dPhm ≈ pPh ≈ mPh), respectively. The result of this study has shown that the rigidity and/or the planarity of a diamine bridge linking the two (2-pyridylmethyl)amine-chelated Pt(II) centres, influences the reactivity of the metal centres by protracting similar symmetry elements within the complexes, which determines the amount of steric influences felt on the coordination square-plane. Hence, the order of reactivity is controlled by both the steric hindrance and the magnitude of the trans σ-inductive effect originating from the linker towards the metal centre. These two factors also impact on the acidity of the complexes. The high negative entropies and low positive enthalpies support an associative mode of activation.     

Dinuclear, bishydrated Gd(III) polyaminocarboxylates with a rigid xylene core display remarkable proton relaxivities

Two novel dinuclear Gd(III) complexes have been synthesized, based on a xylene core substituted with diethylenetriamine-N,N,N',N'-tetraacetate (DTTA) chelators in para or meta position. The complexes [Gd2(pX(DTTA)2)(H2O)4]2- and [Gd2(mX(DTTA)2)(H2O)4]2- both exhibit high complex stability (log K(GdL) = 19.1 and 17.0, respectively), and a good selectivity for Gd(III) against Zn(II), the most abundant endogenous metal ion (log K(ZnL) = 17.94 and 16.19). The water exchange rate is identical within experimental error for the two isomers: k(ex)298 = (9.0 +/- 0.4) x 10(6) s(-1) for [Gd2(pX(DTTA)2)(H2O)4]2- and (8.9 +/- 0.5) x 10(6) s(-1) for [Gd2(mX(DTTA)2)(H2O)4]2-. It is very similar to the k(ex)298 of the structural analogue, bishydrated [Gd(TTAHA)(H2O)2]3-, and about twice as high as that of the monohydrated [Gd(DTPA)(H2O)]2- (TTAHA(6-) = N-tris(2-aminoethyl)amine-N',N',N',N',N',N'-hexaacetate; DTPA(5-) = diethylenetriamine-N,N,N',N',N'-pentaacetate). This relatively fast water exchange can be related to the presence of two inner sphere water molecules which decrease the stereorigidity of the inner sphere thus facilitating the water exchange process. At all frequencies, the water proton relaxivities (r1 = 16.79 and 15.84 mM(-1) s(-1) for the para and meta isomers, respectively; 25 degrees C and 20 MHz) are remarkably higher for the two dinuclear chelates than those of mononuclear commercial contrast agents or previously reported dinuclear Gd(III) complexes. This is mainly the consequence of the two inner-sphere water molecules. In addition, the increased molecular size as compared to monomeric compounds associated with the rigid xylene linker between the two Gd(III) chelating subunits also contributes to an increased relaxivity. However, proton relaxivity is still limited by fast molecular motions which also hinder any beneficial effect of the increased water exchange rate.     

Long-range-distance NMR effects in a protein labeled with a lanthanide-DOTA chelate

A two-thiol reactive lanthanide-DOTA (1,4,7,10-tetraazacyclododecane-N,N',N',N'-tetraacetic acid) chelate, CLaNP-3 (CLaNP=caged lanthanide NMR probe), was synthesized for the rigid attachment to cysteine groups on a protein surface, and used to obtain long-range-distance information from the {15N,1H} HSQC spectra of the protein-lanthanide complex. The DOTA ring exhibits several isomers that are in exchange; however, single resonances were observed for most amide groups in the protein, allowing determination of a single, apparent magnetic-susceptibility tensor. Pseudocontact shifts caused by Yb-containing CLaNP-3 were observed for atoms at 15-35 A from the metal. By using Gd-containing CLaNP-3, relaxation effects were observed, allowing distances up to 30 A from the paramagnetic center to be determined accurately. Similar results were obtained with a Gd-DTPA (diethylene-triaminepentaacetic acid) chelate, CLaNP-1, bound in the same bidentate manner to the protein. This study demonstrates that bidentate attachment of a paramagnetic probe enables determination of long-range distances.     

Toward the rational design of lanthanide coordination polymers: a new topological approach

The implementation of four bidentate building blocks into a high-denticity linker with a flexible spacer leads to a predisposed ligand that allows one to direct the self-assembly of 1D functional coordination polymers. This is illustrated by the assembly under mild conditions of the luminescent metal-organic framework [Tb(Htpabn)] . 14H2O infinity (1; H4tpabn = N,N,N',N'-tetrakis[(6-carboxypyridin-2-yl)methyl]butylenediamine). The X-ray crystal structure shows that the monoprotonated Htpabn binds two equivalent lanthanide ions to form a one-directional staircase chain. The high ligand denticity prevents solvent coordination and leads to a high luminescence quantum yield (Q = 39%), which is maintained after solvent removal.     

Chiral, hemilabile palladium(II) complexes of tridentate oxazolidines, including C2-symmetric "pincers"

Two classes of diastereomerically enriched chiral tridentate ligands incorporating either two oxazolidine and one pyridine ( 1) or two pyridine and one oxazolidine ( 2a-c) donor groups have been made in a high-yielding modular fashion from readily available enantiopure amino alcohols and aldehydes. Both ligand classes readily formed metal complexes via 1:1 reactions with trans-PdCl 2(PhCN) 2. The compounds Pd( 1)Cl 2 and Pd( 2a-c)Cl 2 were formed as mixtures of 3 and 2 diastereomers, respectively, owing to indeterminate absolute configuration at the C (2) position of their constituent oxazolidine rings. Within each diastereomeric manifold, the metal complexes existed as equilibrium mixtures of bi- and tridentate isomers in solution, the interconversion between which was very rapid even at -50 degrees C. The fluxional nature of the compounds was inferred from a combination of (1)H and (15)N NMR spectroscopic and solution conductivity data. Substitution of one chloride ligand for hexafluorophosphate gave as mixtures of diastereomers the salts [Pd( 1-kappa N,kappa (2) N')Cl]PF 6 ( 8) and [Pd( 2a-c-kappa N,kappa N',kappa N')Cl]PF 6 ( 12a-c) in which the ligands were coordinated through all three N-donors. A single recrystallization of 8 gave in optically pure form the major diastereomer 8 ( maj ), which was characterized crystallographically. Complexes of 2a-c differed substantially from those of the bis(pyridylmethyl)amine (bpma) ligand family with which they shared direct atom-for-atom connectivity in the coordinating groups. The amines are known to form exclusively the static tridentate complexes [PdCl(bpma-kappa N,kappa (2) N')]Cl; the difference was attributed to torsional strain associated with the rigid oxazolidine ring in tricoordinated 2a-c.     

Single crystal X-ray structure and optical properties of anthraquinone-based dyes

This study focuses on the preparation, single crystal X-ray diffraction, characterization, and optical properties of some anthraquinone-based dyes. The anthraquinone-based antimicrobial dye N-{2-[(9,10-dioxo-9,10-dihydroanthracen-1-yl)amino]-2-oxoethyl}-N,N-dimethylbutan-1-aminium chloride monohydrate (III) was obtained from 1-aminoanthraquinone (I) via 2-chloro-N-(9,10-dioxo-9,10-dihydroanthracen-1-yl)acetamide (II) using known preparation and characterization methods. Single crystal X-ray diffraction analysis of III revealed a monoclinic system, space group P2₁/n, Z = 4. Photoluminescence properties of anthraquinone dyes I–III were also investigated. These dyes gave an intense emission (λ_max = 341 nm) upon the irradiation by UV light and showed photoluminescence quantum yields of 73 %, 66 %, and 61 % with long excited-state lifetimes of 6.87 ns, 6.14 ns, and 5.69 ns, respectively. These anthraquinone dyes are of interest as an organic light emitting material for electroluminescent devices.     

Ion-pair interactions of lanthanide(III) complexes in aqueous solutions

The formation of ion-pair adducts between the cationic complex La(THP)3+ (THP = 1,4,7,10-tetrakis(2-hydroxypropyl)-1,4,7,10-tetraazacyclododecane) and the anionic complexes Tm(DOTA)- (DOTA = 1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetraacetate), Tm(DTPA)2- (DTPA = diethylenetriamine-N,N,N',N",N"-pentaacetate), Tm(TTHA)3- (TTHA = triethylenetetraamine-N,N,N',N",N"',N"'-hexaacetate), and Tm(DOTP)5- (DOTP = 1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetrakis(methylenephosphonate)) is examined by 13C NMR spectroscopy. The induced 13C shifts of the La(THP)3+ complex are followed by titration of the Tm(III) complexes of DOTA, DTPA, and TTHA at pH 7. From these data, the stability constants are calculated to be beta 1 = 64 M-1 (1:1), beta 1 = 296 M-1 (1:1), and beta 2 = 26,000 M-2 (2:1) for the ion pairs of La(THP)3+, with Tm(DOTA)-, Tm(DTPA)2-, and Tm(TTHA)3-, respectively. The La(THP)3+,Tm(DOTP)5- system elicits chiral resolution of the rapidly interconverting Tm(DOTP)5- isomers.     

2-Oxoalkyl caged oligonucleotides: one-electron reductive activation into emergence of ordinary hybridization property by hypoxic X-irradiation

Ionizing radiation triggers the activation of caged oligodeoxynucleotides (ODNs) with a 2-oxoalkyl leaving group to give the corresponding normal uncaged strands. We designed and synthesized ODNs caged by a 2-oxopropyl group at a given thymine N(3) position (d(oxo)T) to evaluate their one-electron reduction characteristics. Upon hypoxic X-radiolysis in aqueous solution, the caged ODNs released the 2-oxopropyl group to produce the corresponding uncaged ODNs. Digestion by a restriction enzyme Swa I revealed that caged ODN pre-irradiated in hypoxia could form an ordinary duplex with its complementary strand.     

Oxidative DNA strand scission induced by a trinuclear copper(II) complex

A novel trinuclear copper(II) complex, Cu3-L (L = N,N,N',N',N' ',N' '-hexakis(2-pyridyl)-1,3,5-tris(aminomethyl)benzene), exhibited efficient oxidative strand scission of plasmid DNA. The solution behavior of the complex has been studied by potentiometric titration, UV spectroscopy, and cyclic voltammetry. The data showed that there are three redox-active copper ions in the complex with three types of bound water. The complex demonstrated a moderate binding ability for DNA. Cu3-L readily cleaves plasmid DNA in the presence of ascorbate to give nicked (form II) and then linear (form III) products, while the cleavage efficiency using H2O2 is less than by ascorbate, suggesting that the cleavage mode of the trinuclear complex is somewhat different from the traditional Fenton-like catalysis. Meanwhile, Cu3-L is far more efficient than its mononuclear analogue Cu-DPA (DPA = 2,2'-dipyridylamine) at the same [Cu2+] concentration, which suggests a possible synergy between the three or at least two Cu(II) centers in Cu3-L that contributes to its relatively high nucleolytic efficiency. Furthermore, the presence of standard radical scavengers does not have clear effect on the cleavage efficiency, suggesting the reactive intermediates leading to DNA cleavage are not freely diffusible radicals.     

Cobalt(II) complexes of new biomimetic polydentate amide: spectroscopic, kinetics of thermal decomposition and XRPD studies

Complexes of Co(II) with new ligands N',N'-bis(3-carboxy-1-oxoprop-2-enyl) 2-amino-N-arylbenzamidine (C(21)H(17)N(3)O(6)), N',N'-bis(3-carboxy-1-oxopropanyl) 2-amino-N-arylbenzamidine (C(21)H(21)N(3)O(6)) and N',N'-bis(3-carboxy-1-oxophenelenyl) 2-amino-N-arylbenzamidine (C(29)H(21)N(3)O(6)) have been synthesized and characterized by elemental analyses, vibrational spectra, electronic spectra, TOF-mass spectra, magnetic susceptibility measurements, thermal studies and X-ray powder diffraction studies. Vibrational spectra indicate coordination of amide and carboxylate oxygen of the ligands along with two water molecules giving a MO(6) weak field octahedral chromophore. Electronic spectra and magnetic susceptibility measurements reveal octahedral geometry for Co(II) complexes. The elemental analyses and mass spectral data have justified the ML complexes. Kinetic and thermodynamic parameters were computed from the thermal data using Coats and Redfern method, which confirm first-order kinetics. Powder diffraction determines the cell parameters of the complexes.     

Oxidative DNA cleavage promoted by multinuclear copper complexes: activity dependence on the complex structure

Polynuclear copper complexes with two or three Cu(BPA) (BPA, bis(2-pyridylmethyl)amine) motifs, [Cu2(mTPXA)Cl4]3 H2O (1), [Cu2(pTPXA)Cl4]3 H2O (2), [Cu3(HPTAB)Cl5]Cl3 H2O (3) (mTPXA = N,N,N',N'-tetra-(2-pyridylmethyl)-m-xylylene diamine; pTPXA = N,N, N',N'-tetra-(2-pyridylmethyl)-p-xylylenediamine; HPTAB = N,N,N',N',N',N'-hexakis(2-pyridylmethyl)-1,3,5-tris-(aminomethyl)benzene) have been synthesized and characterized. The crystal structures of compounds 2 and 3 showed each Cu(BPA) motif had a 4+1 square-pyramidal coordination environment with one chloride occupying the apical position and three N atoms from the same BPA moiety together with another Cl atom forming the basal plane. Fluorescence and circular dichroism (CD) spectroscopy studies indicated that the DNA binding followed an order of 3>2>1 in the compounds. These complexes cleave plasmid pUC19 DNA by using an oxidative mechanism with mercaptopropionic acid (MPA) as the reductant under aerobic conditions. Dinuclear Cu2+ complexes 1 and 2 showed much higher cleavage efficiency than their mononuclear analogue [Cu(bpa)Cl2] at the same [Cu2+] concentration, suggesting a synergistic effect of the Cu2+ centers. Moreover, the meta-dicopper centers in complex 1 facilitated the formation of linear DNA. Interestingly, the additional copper center to the meta-dicopper motif in complex 3 decreased the cleavage efficacy of meta-dicopper motif in complex 1, although it is able to cleave DNA to the linear form at higher [Cu2+] concentrations. Therefore, the higher DNA binding ability of complex 3 did not lead to higher cleavage efficiency. These findings have been correlated to the DNA binding mode and the ability of the Cu2+ complexes to activate oxygen (O2). This work is a good example of the rational design of multinuclear Cu2+ artificial nuclease and the activity of which can be manipulated by the geometry and the number of metal centers.     

溶液中N-乙酸基取代氮氧杂大环及其配合物稳定性研究

用pH电位滴定法在25℃,0.5mol·L~(-1)KNO_3水溶液中测定了三种大环化合物:H_2L~1(1,12-二氮杂-3,4:9,10-二苯并-5,8-二氧杂环十五烷-N,N＇-二乙酸);H_3L~2(1,12,15-三氮杂-3,4:9,10-二苯并-5,8-二氧杂环十七烷-N,N＇,N″-三乙酸)和H_2L~3(1,15-二氮杂-3,4:12,13-二苯并-5,8,11-三氧杂环十八烷-N,N′-二乙酸)的逐级质子化常数.又测定了它们与Cu~(2+)、Ni~(2+)、Pb~(2+)配合物的稳定常数,以及H_2L~3与镧系金属La~(3+)、Pr~(3+)、Nd~(3+)、Eu~(3+)、Sm~(3+)、Gd~(3+)、Dy~(3+)、Yb~(3+)配合物的稳定常数.讨论了三种大环化合物质子化的一般顺序及其与各种离子配位时稳定性选择规律.说明了影响配位稳定性的有关因素.     

Shape-shifting tetranuclear oxo-bridged manganese cluster: relevance to photosystem II water oxidase active site

The redox properties of the "dimer-of-dimers" complex, [{Mn2(mu-O)2(tphpn)}2]4+ (1) (where Htphpn = N,N,N',N'-tetra(2-methylpyridyl)-2-hydroxypropane-diamine) were investigated. The structure changes dramatically to an adamantane-shaped core upon one-electron oxidation. On the other hand, the one-electron reduced product of 1, [Mn4O4(tphpn)2]3+, exhibits a hyperfine-structured multiline EPR signal very similar to the so-called S0 state of the tetramanganese cluster, which resides at the Photosystem II water oxidase active site.