Cyanostilbene-based near-infrared emissive platinum(II) metallacycles for cancer theranostics

In this work,a near-infrared emissive dipyridyl ligand was synthesized and used to prepare three platinum (II) metallacycles with different shapes via metal-coordination-driven self-assembly with different platinum (II) precursors.These metallacycles were further used for both cell imaging and cancer therapy, offering a new type of theranostic agents towards cancer treatment.     

A STUDY ON CONFIGURATION-ACTIVITY RELATIONSHIP OF DIAMMINEDICHLOROPLATINUM (Ⅱ) BY THE PSEUDOPOTENTIAL VALENCE ELECTRON-ONLY ab initio CALCULATION METHOD

We investigated the cis- and trans-isomers of Pt(NH_3)_2Cl_2 and [Pt(NH_3)_2]~(2+) using a quantum chemical non-empirical calculation method, the pseudopotcntial valence electron only ah initio method. The electronic structure and electrostatic potential counter maps were in turn determined through the wave functions so obtained. There was a sharp difference between the dipole moments of the cis- and trans-isomers. The electrostatic counter maps of the isomers also had remarkably different features. Based on the interaction between the platinum (Ⅱ) coordination compound and the base pairs of nucleic acid, the difference in antitumour activity of the isomeric compounds was discussed, It is pointed out that the key factor for antitumour activity is that the platinum (Ⅱ) coordination compound must be mutually complementary with the target acceptor in both configuration and bonding activity. This mutualcomplementary requirement includes a bonding ability of the platinum complex with two negative centers i     

Extraction chromatographic separation of platinum(IV) from real samples and associated elements

 The extraction behavior of platinum(IV) was studied with N-n-octylaniline as a function of different parameters, such as pH, concentrations of weak acids, mineral acids, reagents and elution time. A selective method was developed for the extraction chromatographic studies of platinum(IV) and its separation from several metal ions with N-n-octylaniline (liquid anion exchanger) as a stationary phase on silica gel. The quantitative extraction of platinum(IV) was observed with 0.067 mol/L N-n-octylaniline and 0.015 mol/L ascorbic acid at pH 1.0. Metal ion was stripped from the column with water and determined spectrophotometrically with stannous chloride method. The proposed method is free from the interference of a large number of cations and anions. Platinum(IV) was separated from pharmaceutical preparations, alloys and synthetic mixtures. Mutual separation scheme was developed for platinum(IV), palladium(II) and gold(III). The log-log plot of N-n-octylaniline concentration versus the distribution ratio indicates that the probable extracted species is ［RR′NH+2 ］· Pt(C6H7O6)－3.     

Coordination-driven self-assembly of dibenzo-18-crown-6 functionalized Pt(Ⅱ) metallacycles

Coordination-driven self-assembly was used to construct two metallacycles of a dicarboxylatefunctionalized dibenzo-18-crown-6 in combination with either a 0° anthracene-based clip-type acceptor or a 60° phenanthrene-based acceptor. The angularities of these moieties make them suitable for the formation of a [2 + 2] rectangle and a [3 + 3] triangle, respectively. The synthesis, characterization and host-guest chemistry of two metallacycles were described and supported by³¹P{¹     

Naphthalimide-rhodamine based fluorescent probe for ratiometric sensing of cellular pH

The pH values of lysosomes in cancer cells is slightly lower than that in normal cells, which can be used to distinguish cancer cells from normal cells. According to this, a naphthalimide-rhodamine based fluorescent probe(hereafter referred to as RBN) with a pK_a of 4.20 was designed and synthesized for ratiometric sensing of cellular pH via fluorescence resonance energy transfer(FRET), which can respond to different pH precisely through ratiometric fluorescence intensity(Ⅰ_(577)/Ⅰ_(540)). RBN can be employed to distinguish cancer cells from normal cells on the basis of different fluorescent response, in particular, RBN showed excellent water solubility and low cell toxicity, all these are quite significant for potential application in cancer diagnose and therapy.     

High enantioselectivity in the asymmetric hydrogenation of ketones by a supported Pt nanocatalyst on a mesoporous modified MCM-41 support

Catalysts containing metal nanotubes were prepared by the adsorption of platinum metal nano‐tubes onto functionalized and modified silica surfaces (MCM‐41 and fumed silica). (3‐Chloropro‐pyl)trimethoxysilane and cinchonidine were used for functionalization and modification, respec‐tively. Potassium chloroplatinate was used as the metal precursor to impregnate platinum metal nanotubes on the pretreated functionalized and modified silica surfaces. The solid catalysts were characterized by ESEM, TEM, EDAX, and XPS. The MCM‐41 supported platinum nanotube catalyst showed>98%to~100%enantioselectivity towards the hydrogenation of a range of pharmaceuti‐cally important chemicals such as methyl pyruvate, ethyl pyruvate, and acetophenone with nearly full conversion.     

Simultaneous Laser Thermal Lens Spectrometric Determination of Trace Platinum and Palladium in an Aquesous Solution

A selective and sensitive method for determination of platinum and palladium(Ⅱ）in an aqueous solution simultaneously by laser thermal lens spectrometry,based on the complex reaction of 2-(3,5-dichloropyridylazo)-5-dimethylaminoamiline(3,5-diCl-PADMA) with platinum and palladium,has been developed.It is shown that the palladium complex can be fromed at room temperature, while the platinum complex can be only formed after being heated in a boiling water bath.By using this difference of reaction temperature and the characteristic of the complexes mentioned above,the method for simultaneous determination of platinum and palladium was established in an aqueous solution without a pre-separation.The results show that the dynamic linear ranges of determination for platinum and palladium are 0.005-0.04μg/mL and 0.005-0.25μg/mL respectively,and that the detection limits are both 0.002/μg/mL.The method has been applied to the determination of platinum and palladium simultaneously in alloy and catalyst samples with satisfactory results.     

Stimuli-responsive cyclometalated platinum complex bearing bent molecular geometry for highly efficient solution-processable OLEDs

Smart materials,such as stimuli-responsive luminescence,have attracted much attentions due to their potential application in semiconductor filed.In this context,platinum complexes of(dfppy-DC)Pt(acac) and(dfppy-O-DC)Pt(acac) were prepared and characterized,in which(2-(4',6'-difluorophenyl)pyridinato-N,C2')(2,4-pentanedionato-0,0)Pt(Ⅱ) was used as the planar emission core and 9-(4-(phenylsulfonyl)phenyl)-9 H-carbazole(DC) was regard as the bent pendent.Both platinum complexes showed bright emission in solution and solid state,concomitant with charming external-stimuli-responsive emission under mechanical grinding,organic solvent vapors and pressure.The change emission color spanned from yellow to near-infrared region.Using the platinum complexes as the dopant,solution processable organic light-emitting diodes(OLEDs) were fabricated and a maximum external quantum efficiency of ~18% was achieved,which is the highest value among the reported solution-processable OLEDs based on externalstimuli-responsive luminescence.This research demonstrated that platinum complex can show promising stimuli responsive emission via ingenious molecular design,indicating a novel way for developing the smart materials in semiconductor filed.     

Photoacoustic imaging-guided chemo-photothermal combinational therapy based on emissive Pt(Ⅱ)metallacycle-loaded biomimic melanin dots

Pt(Ⅱ)-based metallacycles,as an important family of supramolecular coordination complexes(SCCs),have exhibited excellent antitumor activity at the cell level.However,the biomedical applications of Pt(Ⅱ)-based metallacycles for animal studies are still hindered by their poor stability,non-targeted tumour,and lack of detectable feedback for evaluating therapeutic progress.Herein,we propose a strategy that introduces melanin dots as a biomedical platform to load bright-emission Pt(Ⅱ)-based metallacycles,thereby constructing a theranostic agent that enables photoacoustic imaging(PAI)-guided chemo-photothermal combinational therapy.Melanin dots act as a protective carrier to preserve the integrity of Pt(Ⅱ)-based metallacycles before uptake by tumour tissues.Meanwhile,the PAI signal from melanin dots furnishes more comprehensive information on the tumour.Moreover,the heat generated after NIR laser irradiation can not only trigger the apoptosis of tumour cells but also promote the deeper penetration of Pt(Ⅱ)-based SCCs into tumour tissue,thus enhancing the efficiency of chemotherapy.     

Effect of Dai-Bai-Jie on the proliferation and migration of the A549 cells

Lung cancer is the most malignant tumor disease with the highest diagnosis and mortality rate in China.The development of therapeutic drugs is the current research focus.Dai-Bai-Jie is a traditional medicine of the Dai nationality,which is commonly used in the treatment of decreasing swelling,alleviating pain and detoxification.Most of the current researches focused on the component analysis of Dai-Bai-Jie,but few researches studied on its antitumor and pharmacological effect.In this study,we incubated A549 cells with different concentrations of Dai-Bai-Jie.The cell proliferation experiment showed that the DaiBai-Jie solution inhibited the proliferation of A549 cells and caused cell apoptosis.In this work,we confirmed that Dai-Bai-Jie had an inhibitory effect on the proliferation and migration of non-small cell lung cancer A549,which may be used as a novel candidate of anti-tumor therapy for lung cancer patients.     

Aggregation‐Induced Emission of Platinum(II) Metallacycles and Their Ability to Detect Nitroaromatics

Two new acceptors containing platinum–carbazole ( 1 ) and platinum–triphenylamine ( 2 ) backbones with bite angles of 90° and 120°, respectively, have been synthesised and characterised. Reactions of the rigid acceptor 1 with linear dipyridyl‐based donors ( 3 and 4 ) generated [4+4] self‐assembled molecular squares ( 5 and 6 ), and similar treatments with acceptor 2 instead of 1 yielded [6+6] self‐assembled molecular hexagons ( 7 and 8 ). The metallacycles were characterised by multinuclear NMR spectroscopy (¹H and ³¹P) and ESI‐MS. The geometries of the metallacycles were optimised by using the PM6 method. When aggregates of the metallacycles were formed by adding hexane solutions in dichloromethane, aggregation‐induced emission was observed for metallacycles 5 and 7 , and aggregation‐caused quenching was observed for metallacycles 6 and 8 . The formation of aggregates was verified by dynamic light scattering and TEM analyses. Macrocycles 5 and 7 are white‐light emitters in THF. Moreover, their high luminescence in both solution and the solid state was utilised for the recognition of nitroaromatic explosives.     

Platinum Metallacycle-Based Molecular Recognition: Establishment and Application in Spontaneous Formation of a [2]Rotaxane with Light-Harvesting Property

Macrocyclic molecule-based host–guest systems, which provide contributions for the design and construction of functional supramolecular structures, have gained increasing attention in recent years. In particular, platinum(II) metallacycle-based host–guest systems provide opportunities for chemical scientists to prepare novel materials with various functions and structures due to the well-defined shapes and cavity sizes of platinum(II) metallacycles. However, the research on platinum(II) metallacycle-based host–guest systems has been given little attention. In this article, we demonstrate the host–guest complexation between a platinum(II) metallacycle and a polycyclic aromatic hydrocarbon molecule, naphthalene. Taking advantage of metallacycle-based host–guest interactions and the dynamic property of reversible Pt coordination bonds, a [2]rotaxane is efficiently prepared by employing a template-directed clipping procedure. The [2]rotaxane is further applied to the fabrication of an efficient light-harvesting system with multi-step energy transfer process. This work comprises an important supplement to macrocycle-based host–guest systems and demonstrates a strategy for efficient production of well-defined mechanically interlocked molecules with practical values.     

Complexation and extraction of PAHs to the aqueous phase with a dinuclear Pt(II) diazapyrenium-based metallacycle

New palladium and platinum metallacycles have been synthesized by reaction between a 2,7-diazapyrenium-based ligand and Pd(II) and Pt(II) complexes. The inclusion complexes between the metallacycles and polycyclic aromatic hydrocarbons (PAHs) in CD(3)NO(2) and D(2)O were studied by NMR spectroscopy. The structures of the inclusion complexes of the Pt metallacycle as host with pyrene, phenanthrene, and triphenylene were confirmed by single crystal X-ray crystallography. The association constants between the Pt metallacycle and the selected PAHs were determined in CH(3)CN following the characteristic charge-transfer band displayed in their UV/Vis absorption spectrum. Although in aqueous solution all the complexes showed a 1:1 stoichiometry, in CH(3)CN the Job plot indicated a 2:1 stoichiometry for complexes with triphenylene and benzo[a]pyrene. The estimated association constants in water correlate with the hydrophobicity of the PAH, indicating that hydrophobic forces play an important role in the complexation process.     

Platinum(II)-bis-(N-heterocyclic carbene) complexes: synthesis, structure and catalytic activity in the hydrosilylation of alkenes

Chelating biscarbene ligands increase the stability of metal-organic catalyst systems. The catalytic activities of seven structurally different platinum(II)-bis-NHC-complexes in the hydrosilylation of alkenes have been investigated and compared with the catalytic activity of the Karstedt catalyst and of a highly active platinum(0)-NHC-complex. It is shown that a fine-tuning of the catalytic activity of the platinum(II)-bis-NHC-complexes is possible. The synthesis of a platinum(II)-bis-NHC-complex with similar activity, but additional advantages compared to the Karstedt catalyst, is reported. The solid state structure of 1,1-[Bis(3,3′-(4-methoxyphenyl)-1,1′-1H-imidazolium-2,2′-ylidene)methanediyl]platinum(II)-dichloride is presented.     

Highly emissive perylene diimide-based bowtie-shaped metallacycles

Metallacycles hold great promise for fluorescence-based sensing due to their synthetic advantages and unique physicochemical properties. However, it remains highly challenging to develop a versatile methodology for constructing highly emissive metallacycles with targeted functionalities and therefore sought-after properties. Herein, we report a general strategy to construct a series of highly emissive perylene diimide-based metallacycles via the self-assembly of perylene diimide-based tetrapyridyl ligand with different dicarboxylic ligands featuring fixed angles and cis-Pt(PEt₃)₂(OTf)₂. Single crystal X-ray diffraction analyses verify the formation of bowtie-like metallacycles with two triangular cavities. Notably, the fluorescence quantum yields of most assemblies exceed 98%, amongst the highest values for metallacycles. Additionally, such metallacycles exhibit sensitive fluorescence responses toward picric acid with a detection limit of 2.8 × 10^?6 mol/L. This study not only provides a rational strategy for preparing highly emissive bowtie-shaped metallacycles, but also sheds light on their usage in the detection of picric acid and associated compounds.     

Gondola-shaped tetra-rhenium metallacycles modified evanescent wave infrared chemical sensors for selective determination of volatile organic compounds

Water-stable and cavity-contained rhenium metallacycles were synthesized, and their ability to selectively interact with volatile organic compounds (VOCs) systematically studied using attenuated total reflection infrared (ATR-IR) spectroscopy. Integrating the unique properties of rhenium metallacycles into optical sensing technologies significantly improves selectivity in detecting aromatic compounds. To explore the interaction of rhenium metallacycles with VOCs, the surface of ATR sensing elements was modified with the synthesized rhenium metallacycles and used to detect VOCs. The results indicate that rhenium metallacycles have crown ether-like recognition sites, which can selectively interact with aromatic compounds, especially those bearing polar functional groups. The IR absorption bands of rhenium metallacycles shift significantly upon adsorption of aromatic VOCs, revealing a strong interaction between the tetra-rhenium metallacycles and guest aromatic compounds. Optimizing the thickness of the metallacycles coated on the surface of the sensing element led to rapid response in detection. The dynamic range of response was generally up to 30 mg/L with detection limits ca. 30 μg/L. Further studies of the effect of interferences indicate that recovery can be higher than 95% for most of the compounds tested. The results on the flow-cell device indicated that the performances were similar to a static detection system but the detection of VOCs can be largely simplified.     

Aurophilicity versus mercurophilicity: impact of d10-d10 metallophilic interactions on the structure of metal-rich supramolecular assemblies

Treatment of U-shaped, binuclear Cu(I) complexes 1,1' (1, counterion: BF(4)(-); 1', counterion: PF(6)(-)) with metal cyanide linear linkers K[Au(CN)(2)] (3) and Hg(CN)(2) (4) lead to formation of new supramolecular assemblies 5,5' and 6,6', respectively, in good yield. These derivatives have been characterized by NMR spectroscopy, IR, and X-ray diffraction studies. Derivative 5,5' are supramolecular metallacycles in which intramolecular aurophilic interactions between the Au(I) metal centers of the linkers are observed. Derivative 5 crystallizes as a single solid phase, whereas derivative 5' is characterized in the solid state as four different pseudo-polymorphs (5'a-d). Notably in the case of phase 5'd, a dimer of supramolecular metallacycles bounded by intermolecular aurophilic interactions is formed. Conversely, derivatives 6,6' present large structural diversity depending on the nature of the counterion. Derivative 6 is a supramolecular rectangle in which the Hg(II)-Hg(II) metal distance suggests mercurophilic interaction, whereas 6' crystallizes as two different pseudo-polymorphs 6'a,b, that is, a one-dimensional coordination polymer and one oligomer with no short Hg(II)-Hg(II) metal contacts, respectively. In derivatives 6,6', short contacts between the Hg(II) metal centers and fluorine atoms of the counterions are also observed, which may explain the counterion structural dependence of these supramolecular assemblies based on Hg(II) metal cyanide linker. Comparison of the different solid-state structures characterized highlights the importance of weak secondary interactions between the linkers for the formation supramolecular metallacycles from molecular clips 1,1' and suggests the range of energies required for these interactions to form metallacycles and to induce self-aggregation.     

Quantitative bioimaging of platinum group elements in tumor spheroids

Limited drug penetration into tumor tissue is a significant factor to the effectiveness of cancer therapy. Tumor spheroids, a 3D cell culture model system, can be used to study drug penetration for pharmaceutical development. In this study, a method for quantitative bioimaging of platinum group elements by laser ablation (LA) coupled to inductively coupled plasma mass spectrometry (ICP-MS) is presented. Different matrix-matched standards were used to develop a quantitative LA-ICP-MS method with high spatial resolution. To investigate drug penetration, tumor spheroids were incubated with platinum complexes (Pt(II)acetylacetonate, cisplatin) and the palladium tagged photosensitizer 5,10,15,20-tetrakis(3-hydroxyphenyl)porphyrin (mTHPP). Distribution and accumulation of the pharmaceuticals were determined with the developed method.     

Construction of Alkynylplatinum(II) Bzimpy‐Functionalized Metallacycles and Their Hierarchical Self‐Assembly Behavior in Solution Promoted by Pt⋅⋅⋅Pt and π–π Interactions

A family of new alkynylplatinum(II) 2,6‐bis(benzimidazol‐2′‐yl)pyridine (bzimpy)‐functionalized supramolecular metallacycles with different shapes and sizes have been successfully prepared by coordination‐driven self‐assembly. The obtained metallacycles showed switchable emission and a strong tendency to form intermolecular Pt???Pt and π–π stacking interactions in solution that were not displayed by their individual precursors. Further investigation revealed that the existence of the metallacyclic scaffold at the core could facilitate the formation of intermolecular Pt???Pt and π–π stacking interactions of peripheral alkynylplatinum(II) bzimpy units. Moreover, the shapes and sizes of the metallacyclic scaffold have a significant influence on the hierarchical self‐assembly behavior. Among the three metallacycles, hexagonal metallacycle A , with a relatively small size, could spontaneously self‐assemble into an aromatic guest stimuli‐responsive metallogel at room temperature without a heating–cooling process.