Molecular Recognition of Nucleotides in Water by Scorpiand‐Type Receptors Based on Nucleobase Discrimination

The detection of nucleotides is of crucial importance because they are the basic building blocks of nucleic acids. Scorpiand‐based polyamine receptors functionalized with pyridine or anthracene units are able to form stable complexes with nucleotides in water, based on coulombic, π–π stacking, and hydrogen‐bonding interactions. This behavior has been rationalized by means of an exploration with NMR spectroscopy and DFT calculations. Binding constants were determined by potentiometry. Fluorescence spectroscopy studies have revealed the potential of these receptors as sensors to effectively and selectively distinguish guanosine‐5′‐triphosphate (GTP) from adenosine‐5′‐triphosphate (ATP).     

核苷酸碱基堆积导致的分子间NOE交叉峰

ＡＴＰ(三磷酸腺苷)是生命活动中不可缺少的能量物质,它的各种结合状态都是与生物功能密切相关的.在生物体内,它常常以很高的浓度存在[1-3].由于碱基芳环部分的电子云形成环流,两两堆积可以降低能量.因此在ＡＴＰ浓溶液中,它们可能倾向于以碱基堆积方式形成自聚体,使能量得到降低.已有不少报导指出核苷酸在溶液中有碱基堆积现象.人们通过改变样品的浓度、ｐＨ值、实验温度等条件,发现ＡＴＰ溶液的1ＨＮＭＲ谱中各质子的化学位移有很大变化,据此提出了多种可能的堆积模型[4-7],并通过实验数据计算了它们的变化规律[8,9],认为在酸度较高的情况…     

A Fluxional Copper Acetylide Cluster in CuAAC Catalysis

A molecularly defined copper acetylide cluster with ancillary N‐heterocyclic carbene (NHC) ligands was prepared under acidic reaction conditions. This cluster is the first molecular copper acetylide complex that features high activity in copper‐catalyzed azide–alkyne cycloadditions (CuAAC) with added acetic acid even at ?5 °C. Ethyl propiolate protonates the acetate ligands of the dinuclear precursor complex to release acetic acid and replaces one out of four ancillary ligands. Two copper(I) ions are thereby liberated to form the core of a yellow dicationic C₂‐symmetric hexa‐NHC octacopper hexaacetylide cluster. Coalescence phenomena in low‐temperature NMR experiments reveal fluxionality that leads to the facile interconversion of all of the NHC and acetylide positions. Kinetic investigations provide insight into the influence of copper acetylide coordination modes and the acetic acid on catalytic activity. The interdependence of “click” activity and copper acetylide aggregation beyond dinuclear intermediates adds a new dimension of complexity to our mechanistic understanding of the CuAAC reaction.     

Pincer‐Type Platinum(II) Complexes Containing N‐Heterocyclic Carbene (NHC) Ligand: Structures,Photophysical and Anion‐Binding Properties,and Anticancer Activities

Two classes of pincer‐type Pt^II complexes containing tridentate N‐donor ligands ( 1 – 8 ) or C‐deprotonated N^C^N ligands derived from 1,3‐di(2‐pyridyl)benzene ( 10 – 13 ) and auxiliary N‐heterocyclic carbene (NHC) ligand were synthesized. [Pt(trpy)(NHC)]²⁺ complexes 1 – 5 display green phosphorescence in CH₂Cl₂ (Φ: 1.1–5.3 %; τ: 0.3–1.0 μs) at room temperature. Moderate‐to‐intense emissions are observed for 1 – 7 in glassy solutions at 77 K and for 1 – 6 in the solid state. The [Pt(N^C^N)(NHC)]⁺ complexes 10 – 13 display strong green phosphorescence with quantum yields up to 65 % in CHCl₃. The reactions of 1 with a wide variety of anions were examined in various solvents. The tridentate N‐donor ligand of 1 undergoes displacement reaction with CN^? in protic solvents. Similar displacement of the N^C^N ligand by CN^? has been observed for 10 , leading to a luminescence “switch‐off” response. The water‐soluble 7 containing anthracenyl‐functionalized NHC ligand acts as a light “switch‐on” sensor for the detection of CN^? ion with high selectivity. The in vitro cytotoxicity of the Pt^II complexes towards HeLa cells has been evaluated. Complex 12 showed high cytotoxicity with IC₅₀ value of 0.46 μM , whereas 1 – 4 and 6 – 8 are less cytotoxic. The cellular localization of the strongly luminescent complex 12 traced by using emission microscopy revealed that it mainly localizes in the cytoplasmic structures rather than in the nucleus. This complex can induce mitochondria dysfunction and subsequent cell death.     

ATP‐Releasing Nucleotides: Linking DNA Synthesis to Luciferase Signaling

A new strategy is reported for the production of luminescence signals from DNA synthesis through the use of chimeric nucleoside tetraphosphate dimers in which ATP, rather than pyrophosphate, is the leaving group. ATP‐releasing nucleotides (ARNs) were synthesized as derivatives of the four canonical nucleotides. All four derivatives are good substrates for DNA polymerase, with K_m values averaging 13‐fold higher than those of natural dNTPs, and k_cat values within 1.5‐fold of those of native nucleotides. Importantly, ARNs were found to yield very little background signal with luciferase. DNA synthesis experiments show that the ATP byproduct can be harnessed to elicit a chemiluminescence signal in the presence of luciferase. When using a polymerase together with the chimeric nucleotides, target DNAs/RNAs trigger the release of stoichiometrically large quantities of ATP, thereby allowing sensitive isothermal luminescence detection of nucleic acids as diverse as phage DNAs and short miRNAs.     

Quantitative Monitoring and Visualization of Hydrogen Sulfide In Vivo Using a Luminescent Probe Based on a Ruthenium(II) Complex

Development of novel bioanalytical methods for monitoring of H₂S is key toward understanding the physiological and pathological functions of this gasotransmitter in live organisms. A ruthenium(II)‐complex‐based luminescence probe, Ru‐MDB (MDB: 4’‐methyl‐[2,2’‐bipyridine]‐4‐yl)methyl 2‐((2,4‐dinitrophenyl)thio)benzoate), was developed by introducing a new H₂S responsive masking moiety to a red‐emitting Ru^II luminophore. Cleavage of this masking group by a H₂S‐triggered reaction leads to a luminescence “off–on” response. The long‐lived emissions of Ru‐MDB and its reaction product with H₂S allowed quantitative detection of H₂S in autofluorescence‐rich human sera and adult zebrafish organs using the time‐gated luminescence mode. Ru‐MDB exhibits red emission, a large Stokes shift, high specificity and sensitivity for H₂S detection, and low cytotoxicity, which enables imaging and flow cytometry analysis of lysosomal H₂S generation in live inflamed cells under drug stimulation. Monitoring of H₂S in live Daphnia magna, zebrafish embryos, adult zebrafish, and mice, was conducted by in vivo imaging using Ru‐MDB as a probe.     

Multistimuli‐Responsive Luminescence Switching of Pyrazine Derivative Based Donor–Acceptor–Donor Luminophores

Three symmetrical donor–acceptor–donor (D–A–D) luminophores ( C1 , C2 , and C3 ) with pyrazine derivatives as electron‐withdrawing groups have been developed for multistimuli‐responsive luminescence switching. For comparison, reference compounds R1 and R2 without the pyrazine moiety have also been synthesized. Intramolecular charge transfer (ICT) interactions can be found for all D–A–D luminophores owing to the electron‐withdrawing properties of the two imine nitrogen atoms in the pyrazine ring and the electron‐donating properties of the other two amine nitrogen atoms in the two triphenylamine units. Moreover, luminophores C1 , C2 , and C3 exhibit “on–off–on” luminescence switching properties in mixtures of water/tetrahydrofuran with increasing water content, which is different from the “on–off” switching for typical aggregation‐caused quenching (ACQ) materials and “off–on” switching for traditional aggregation‐induced emission (AIE) materials. Additionally, upon grinding the pristine samples, luminophores C1 , C2 , and C3 display bathochromically shifted photoluminescence maxima that can be recovered by either solvent fuming or thermal annealing treatments. The piezofluorochromic (PFC) properties are more pronounced than those for reference compounds R1 and R2 , which indicates that D–A molecules have the ability to amplify the PFC effect by tuning the ICT interactions upon tiny structural changes under pressure. Furthermore, the target luminophores demonstrate acid‐responsive photoluminescence spectra that can be recovered in either basic or ambient environments. These results suggest that D–A complexes are potential candidates for multistimuli‐responsive luminescence switching because their ICT profiles can be facilely tuned with tiny external stimuli.     

Simulating GTP:Mg and GDP:Mg with a simple force field: A structural and thermodynamic analysis

Di‐ and tri‐phosphate nucleotides are essential cofactors for many proteins, usually in an Mg²⁺‐bound form. Proteins like GTPases often detect the difference between NDP and NTP and respond by changing conformations. To study such complexes, simple, fixed charge force fields have been used, which allow long simulations and precise free energy calculations. The preference for NTP or NDP binding depends on many factors, including ligand structure and Mg²⁺ coordination and the changes they undergo upon binding. Here, we use a simple force field to examine two Mg²⁺ coordination modes for the unbound GDP and GTP: direct, or “Inner Sphere” (IS) coordination by one or more phosphate oxygens and indirect, “Outer Sphere” (OS) coordination involving one or more bridging waters. We compare GTP: and GDP:Mg binding with OS and IS coordination; combining the results with experimental data then indicates that GTP prefers the latter. We also examine different kinds of IS coordination and their sensitivity to a key force field parameter: the optimal Mg:oxygen van der Waals distance R_min. Increasing R_min improves the Mg:oxygen distances, the GTP: and GDP:Mg binding affinities, and the fraction of GTP:Mg with β + γ phosphate coordination, but does not improve or change the GTP/GDP affinity difference, which remains much larger than experiment. It has no effect on the free energy of GDP binding to a GTPase. © 2012 Wiley Periodicals, Inc.     

Supramolecular Fluorescent Nanoparticles Constructed via Multiple Non‐Covalent Interactions for the Detection of Hydrogen Peroxide in Cancer Cells

Overabundance of hydrogen peroxide originating from environmental stress and/or genetic mutation can lead to pathological conditions. Thus, the highly sensitive detection of H₂O₂ is important. Herein, supramolecular fluorescent nanoparticles self‐assembled from fluorescein isothiocyanate modified β‐cyclodextrin (FITC‐β‐CD)/rhodamine B modified ferrocene (Fc‐RB) amphiphile were prepared through host–guest interaction between FITC‐β‐CD host and Fc‐RB guest for H₂O₂ detection in cancer cells. The self‐assembled nanoparticles based on a combination of multiple non‐covalent interactions in aqueous medium showed high sensitivity to H₂O₂ while maintaining stability under physiological condition. Owing to the fluorescence resonance energy transfer (FRET) effect, addition of H₂O₂ led to obvious fluorescence change of nanoparticles from red (RB) to green (FITC) in fluorescent experiments. In vitro study showed the fluorescent nanoparticles could be efficiently internalized by cancer cells and then disrupted by endogenous H₂O₂, accompanying with FRET from “on” to “off”. These supramolecular fluorescent nanoparticles constructed via multiple non‐covalent interactions are expected to have potential applications in diagnosis and imaging of diseases caused by oxidative stresses.     

An Iminocoumarin Sulfonamide Based Turn‐On Fluorescent Probe for the Detection of Biothiols in Aqueous Solution

A new chemodosimeter for the highly selective sensing and imaging of biothiols was designed and realized in phosphate‐buffered saline solution at pH 7.4 through a fluorescence “off–on” response. A unique mechanism featuring a two‐step cascade (biothiols→H₂O) sequence for this remarkable recognition is disclosed for the first time.     

“Off‐on‐off” Fluorescence pH Switch of Three Trinuclear RuII Complexes Containing Imidazole Rings

Three tripodal ligands H₃L^1–3 containing imidazole rings were synthesized by the reaction of 1,10‐phenanthroline‐5,6‐dione with 1,3,5‐tris[(3‐formylphenoxy)methyl]benzene, 1,3,5‐tris[(3‐formylphenoxy)methyl]‐2,4,6‐trimethylbenzene, and 2,2′,2"‐tris[(3‐formylphenoxy)ethyl]amine, respectively. Trinuclear Ru^II polypyridyl complexes [(bpy)₆Ru₃H₃L^1–3](PF₆)₆ were prepared by the condensation of Ru(bpy)₂Cl₂ · 2H₂O with ligands H₃L^1–3. The pH effects on the UV/Vis absorption and fluorescence spectra of the three complexes were studied, and ground‐ and excited‐state ionization constants of the three complexes were derived. The three complexes act as “off‐on‐off” fluorescence pH switch through protonation and deprotonation of imidazole ring with a maximum on‐off ratio of 5 in buffer solution at room temperature.     

Multidentate Europium Chelates as Luminoionophores for Anion Recognition: Impact of Ligand Design on Sensitivity and Selectivity,and Applicability to Enzymatic Assays

The design of photoluminescent molecular probes for the selective recognition of anions is a major challenge for the development of optical chemical sensors. The reversible binding of anions to lanthanide centers is one promising option for the realization of anion sensors, because it leads in some cases to a strong luminescence increase by the replacement of quenching water molecules. Yet, it is an open problem to gain control of the sensitivity and selectivity of the luminescence response. Primarily, the selective detection of (poly)phosphate species such as nucleotides has emerged as a demanding task, because they are involved in many biological processes and enzymatic reactions. We designed a series of pyridyl‐based multidentate europium complexes (seven‐, six‐, and five‐dentate) including sensitizing chromophores and studied their luminescence intensity and lifetime responses to different (poly)phosphates (adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP), cyclic adenosine monophosphate (cAMP), pyrophosphate, and phosphate anions), and carboxyanions (citrate, malate, oxalacetate, succinate, α‐ketoglutarate, pyruvate, oxalate, carbonate). The results reveal that the number of free coordination sites has a significant impact on the sensitivity and selectivity of the response. Because of its reversibility, the lanthanide probes can be applied to monitor the activity of ATP‐consuming enzymes such ATPases and apyrases, which is demonstrated by means of the five‐dentate complex.     

Luminescent Quantum Clusters of Gold in Bulk by Albumin‐Induced Core Etching of Nanoparticles: Metal Ion Sensing,Metal‐Enhanced Luminescence,and Biolabeling

The synthesis of a luminescent quantum cluster (QC) of gold with a quantum yield of ～4 % is reported. It was synthesized in gram quantities by the core etching of mercaptosuccinic acid protected gold nanoparticles by bovine serum albumin (BSA), abbreviated as Au_QC@BSA. The cluster was characterized and a core of Au₃₈ was assigned tentatively from mass spectrometric analysis. Luminescence of the QC is exploited as a “turn‐off” sensor for Cu²⁺ ions and a “turn‐on” sensor for glutathione detection. Metal‐enhanced luminescence (MEL) of this QC in the presence of silver nanoparticles is demonstrated and a ninefold maximum enhancement is seen. This is the first report of the observation of MEL from QCs. Folic acid conjugated Au_QC@BSA was found to be internalized to a significant extent by oral carcinoma KB cells through folic acid mediated endocytosis. The inherent luminescence of the internalized Au_QC@BSA was used in cell imaging.     

Remarkable luminescence properties of lanthanide complexes with asymmetric dodecahedron structures

The distorted coordination structures and luminescence properties of novel lanthanide complexes with oxo‐linked bidentate phosphane oxide ligands—4,5‐bis(diphenylphosphoryl)‐9,9‐dimethylxanthene (xantpo), 4,5‐bis(di‐tert‐butylphosphoryl)‐9,9‐dimethylxanthene (tBu‐xantpo), and bis[(2‐diphenylphosphoryl)phenyl] ether (dpepo)—and low‐vibrational frequency hexafluoroacetylacetonato (hfa) ligands are reported. The lanthanide complexes exhibit characteristic square antiprism and trigonal dodecahedron structures with eight‐coordinated oxygen atoms. The luminescence properties of these complexes are characterized by their emission quantum yields, emission lifetimes, and their radiative and nonradiative rate constants. Lanthanide complexes with dodecahedron structures offer markedly high emission quantum yields (Eu: 55–72 %, Sm: 2.4–5.0 % in [D₆]acetone) due to enhancement of the electric dipole transition and suppression of vibrational relaxation. These remarkable luminescence properties are elucidated in terms of their distorted coordination structures.     

Metal–Carbonyl Units for Vibrational and Luminescence Imaging: Towards Multimodality

Metal–carbonyl complexes are attractive structures for bio‐imaging. In addition to unique vibrational properties due to the CO moieties enabling IR and Raman cell imaging, the appropriate choice of ancillary ligands opens up the opportunity for luminescence detection. Through a classification by techniques, past and recent developments in the application of metal–carbonyl complexes for vibrational and luminescence bio‐imaging are reviewed. Finally, their potential as bimodal IR and luminescent probes is addressed.     

Molecular “Multi‐rod Cable” {[Co(NC5H4–CH=CH–C6H4–CH=CH–C5H4N)(HCOO)2]8}n: A Novel Supramolecular Architecture by Cooperation of Coordination and Stacking Interactions

The cobalt‐formate coordination polymers {[Co(bpyph)(HCOO)₂]₈}_n ( 1 ) (bpyph = 1,4‐bis(2‐(4‐pyridyl)ethenyl)benzene) and {[Co(HCONH₂)₂(HCOO)₂]}_n ( 2 ) have been prepared by interaction of Co(NO₃)₂ · 6 H₂O in formamide solution with generation of formate anion by hydrolysis of the solvent. Coordination polymer 1 reveals an unprecedented example of “molecular multi‐rod cable” architecture, in which eight single “molecular wires” {[Co(bpyph)]}_n are interlinked by bridging formate anions to give infinite octameric chains. The formate groups adopt mono‐, and bi‐ and tridentate bridging and chelate modes of coordination (Co–O 1.966–2.134 Å). The coordination geometry around the cobalt atoms is essentially dominated by the demands for most effective packing of parallel situated polycyclic aromatic ligands, with extensive CH…π, or edge‐to‐face stacking interactions within the single octameric chain as well as between the closest neighbours (C…C separations within this stack are ca. 3.50 Å).     

Proof of Potassium Ions by Luminescence Signaling Based on Weak Gold–Gold Interactions in Dinuclear Gold(I) Complexes

Two versatile luminescence ion probes for potassium ions have been designed based on the “switching on and off” of the gold–gold interaction. Addition of potassium ions to the gold(I ) complexes [Au₂(R₂PCH₂PR₂)(S-benzo[15]crown-5)₂] (see the picture; R=Ph, cyclohexyl; M⁺=K⁺) give rise to an intense red luminescence.     

Jumping Crystals of Pyrene Tweezers: Crystal‐to‐Crystal Transition Involving π/π‐to‐CH/π Assembly Mode Switching

Crystals of pyrene tweezers 1 with interdigitating pyrenyl blades jump vigorously at around 160 °C. Single‐crystal X‐ray diffraction analysis before jumping revealed the presence of a “pyrene tetrad” in the crystal lattice, where four pyrenyl blades are π ‐stacked on top of each other. Upon heating the crystal to induce the jumping event, inner two pyrenyl blades in the “pyrene tetrad” probably rotate to switch off their π ‐stacking interaction with the neighboring outer pyrenyl blades and form new CH−π bonds. Different from reported salient crystals, our crystal jumps with the release of CHCl₃ as inclusion solvent.     

Self‐Assembled Hexanuclear Organometallic Cages: Synthesis,Characterization, and Host–Guest Properties

A series of iridium‐ and rhodium‐based hexanuclear organometallic cages containing 2,5‐dichloro‐3,6‐dihydroxy‐1,4‐benzoquinone, 9,10‐dihydroxy‐1,4‐anthraquinone, and 6,11‐dihydroxynaphthacene‐5,12‐dione ligands were synthesized from the self‐assembly of the corresponding molecular “clips” and 2,4,6‐tri(4‐pyridyl)‐1,3,5‐triazine ligands in good yields. These organometallic cages can form inclusion systems with a wide variety of π‐donor substrates, including coronene, pyrene, [Pt(acac)₂], and hexamethoxytriphenylene. The 1:1 complexation of the resulting supramolecular assemblies was confirmed by ¹H NMR spectroscopy. Large complexation shifts (Δδ>1 ppm) were observed in the ¹H NMR spectra of guests in the presence of cage [Cp*₆M₆(μ‐DHNA)₃(tpt)₂](OTf)₆ ( 6a ; M=Ir, tpt=2,4,6‐tri(4‐pyridyl)‐1,3,5‐triazine). The formation of discrete 1:1 donor–acceptor complexes, pyrene ?6 b (M=Rh), coronene ?6 a , coronene ?6 b , and [Pt(acac)₂] ?6 a was confirmed by their single‐crystal X‐ray analyses. In these systems, the most important driving force for the formation of guest–host complexes is clearly the donor–acceptor π???π stacking interaction, including charge‐transfer interactions between the electron‐donating and electron‐accepting aromatic components. These structures provide compelling evidence for the existence of strong attractive forces between the electron‐deficient triazine core and electron‐rich guest. The results presented here may provide useful guidance for designing artificial receptors for functional biomolecules.     

A pyrophosphate-responsive gadolinium(III) MRI contrast agent

This study shows that the relaxivity and optical properties of functionalised lanthanide‐DTPA‐bis‐amide complexes (lanthanide=Gd³⁺ and Eu³⁺, DTPA=diethylene triamine pentaacetic acid) can be successfully modulated by addition of specific anions, without direct Ln³⁺/anion coordination. Zinc(II)‐dipicolylamine moieties, which are known to bind strongly to phosphates, were introduced in the amide “arms” of these ligands, and the interaction of the resulting Gd–Zn₂ complexes with a range of anions was screened by using indicator displacement assays (IDAs). Considerable selectivity for polyphosphorylated species (such as pyrophosphate and adenosine‐5′‐triphosphate (ATP)) over a range of other anions (including monophosphorylated anions) was apparent. In addition, we show that pyrophosphate modulates the relaxivity of the gadolinium(III) complex, this modulation being sufficiently large to be observed in imaging experiments. To establish the binding mode of the pyrophosphate and gain insight into the origin of the relaxometric modulation, a series of studies including UV/Vis and emission spectroscopy, luminescence lifetime measurements in H₂O and D₂O, ¹⁷O and ³¹P NMR spectroscopy and nuclear magnetic resonance dispersion (NMRD) studies were carried out.