(Metallo)porphyrins as Potent Phototoxic Anti‐Cancer Agents after Irradiation with Red Light

Novel photoactive (metallo)porphyrins were synthesised and characterised. When irradiated with light at a wavelength greater than 600 nm, these porphyrins act as photosensitisers and show high cytotoxicity towards two different human cancer cell lines with IC₅₀ values down to 0.4 μM . A paramagnetic copper(II) porphyrin is the first photosensitiser to display excellent phototoxicity, explained by the electron paramagnetic resonance (EPR) spin trapping of hydroxy radicals and experimentally confirmed by the discovery of elevated levels of reactive oxygen species (ROS) inside A2780 cells after irradiation with red light. This finding indicates that paramagnetic compounds should be considered for photodynamic therapy (PDT). Furthermore, an additive effect of cisplatin and a zinc porphyrin, both at subtherapeutic concentrations of 0.22 μm, was observed.     

Photocatalytic Hydrogen Evolution Based on Efficient Energy and Electron Transfers in Donor–Bridge–Acceptor Multibranched‐Porphyrin‐Functionalized Platinum Nanocomposites

Two donor–bridge–acceptor conjugates (5,10,15,20‐tetrakis[4‐(N,N‐diphenylaminobenzoate)phenyl] porphyrin (TPPZ) and 5,10,15,20‐tetrakis[4‐(N,N‐diphenylaminostyryl)phenyl] porphyrin (TPPX)) were covalently linked to triphenylamine (TPA) at the meso‐position of porphyrin ring. The triphenylamine entities were expected to act as energy donors and the porphyrins to act as an energy acceptor. In this paper, we report on the synthesis of these multibranched‐porphyrin‐functionalized Pt nanocomposites. The conjugates used here not only served as a stabilizer to prevent agglomeration of Pt nanoparticles, but also as a light‐harvesting photosensitizer. The occurrence of photoinduced electron‐transfer processes was confirmed by time‐resolved fluorescence and photoelectrochemical spectral measurements. The different efficiencies for energy and electron transfer in the two multibranched porphyrins and the functionalized Pt nanocomposites were attributed to diverse covalent linkages. Moreover, in the reduction of water to produce H₂, the photocatalytic activity of the Pt nanocomposite functionalized by TPPX, in which the triphenylamine and porphyrin moieties are bonded through an ethylene bridge, was much higher than that of the platinum nanocomposite functionalized by TPPZ, in which the two moieties are bonded through an ester. This investigation demonstrates the fundamental advantages of constructing donor–bridge–acceptor conjugates as highly efficient photosensitizers based on efficient energy and electron transfer.     

Carbon‐bridged Oligo(phenylenevinylene)s as Light‐harvesting Antenna for Porphyrins

The efficacy of carbon‐bridged oligo(phenylenevinylenes)s (COPVs) as light‐harvesting antenna for porphyrins is demonstrated using a series of 5,15‐di‐COPVn‐substituted free‐base and zinc porphyrins, COPVn‐MP‐COPVn (n=1–3, M=H₂, Zn). These molecules were synthesized by Suzuki–Miyaura cross‐coupling reactions of COPVn‐Bpin and Br‐H₂P‐Br . The absorption spectra of these compounds in solution show a significant expansion of the Soret band region together with a bathochromic shift of the Q band, suggesting a significant interaction between these chromophores in the ground state. The photoluminescence quantum yield of the porphyrin‐COPV conjugates is enhanced up to four times relative to the parent porphyrins. Theoretical calculations also indicated interactions between these chromophores in the HOMO, which suggests that the light‐harvesting ability stems from the expansion of the π‐electron‐conjugation system.     

Boron‐Containing Protoporphyrin IX Derivatives and Their Modification for Boron Neutron Capture Therapy: Synthesis,Characterization, and Comparative In Vitro Toxicity Evaluation

A novel series of boronated porphyrins for potential use in boron neutron capture therapy (BNCT) and photodynamic therapy (PDT) for tumor suppression is described. Protoporphyrin IX {i.e., bis(α‐methyl‐β‐pentylethylether)protoporphyrin IX, and bis(α‐methyl‐β‐dodecanylethylether)protoporphyrin IX} bearing polyhedral borane anions (B₁₂H₁₁SH^2?, B₁₂H₁₁NH₃^?, or B₁₂H₁₁OH^2?) were synthesized with reasonable yields. Modification of the protoporphyrin IX structure was achieved by variation of the lengths of the alkyl chains (pentyl and dodecanyl) attached through ether linkages to the former vinyl groups. The goal of this modification was to develop boronated porphyrins with chemical and physical properties that differed from those of protoporphyrin IX. Performance of an MTT assay with each derivative revealed that the synthesized boronated porphyrins showed low cytotoxicities in a variety of cancer cells. Of these compounds, B₁₂H₁₁NH₂^2?‐conjugated porphyrin induced a significant increase in the level of boron accumulation and PDT efficacy against HeLa cells.     

Rational design of iridium–porphyrin conjugates for novel synergistic photodynamic and photothermal therapy anticancer agents

Near-infrared (NIR) emitters are important probes for biomedical applications. Nanoparticles (NPs) incorporating mono- and tetranuclear iridium(iii) complexes attached to a porphyrin core have been synthesized. They possess deep-red absorbance, long-wavelength excitation (635 nm) and NIR emission (720 nm). TD-DFT calculations demonstrate that the iridium–porphyrin conjugates herein combine the respective advantages of small organic molecules and transition metal complexes as photosensitizers (PSs): (i) the conjugates retain the long-wavelength excitation and NIR emission of porphyrin itself; (ii) the conjugates possess highly effective intersystem crossing (ISC) to obtain a considerably more long-lived triplet photoexcited state. These photoexcited states do not have the usual radiative behavior of phosphorescent Ir(iii) complexes, and they play a very important role in promoting the singlet oxygen (¹O₂) and heat generation required for photodynamic therapy (PDT) and photothermal therapy (PTT). The tetranuclear 4-Ir NPs exhibit high ¹O₂ generation ability, outstanding photothermal conversion efficiency (49.5%), good biocompatibility, low half-maximal inhibitory concentration (IC₅₀) (0.057 μM), excellent photothermal imaging and synergistic PDT and PTT under 635 nm laser irradiation. To our knowledge this is the first example of iridium–porphyrin conjugates as PSs for photothermal imaging-guided synergistic PDT and PTT treatment in vivo.

Iridium–porphyrin conjugates assembled in nanoparticles are photosensitizers that exhibit excellent photothermal imaging and synergistic PDT and PTT in vivo.     

Design,synthesis of (Z)‐3‐benzyl‐5‐((1‐phenyl‐3‐(3‐((1‐ substituted phenyl‐1H‐1,2,3‐triazol‐4‐yl)methoxy)phenyl)‐1H‐pyrazol‐4‐yl)methylene)thiazolidine‐2,4‐dione analogues as potential cytotoxic agents

In an attempt to achieve promising cytotoxic agents, a series of new (Z)‐3‐benzyl‐5‐((1‐phenyl‐3‐(3‐((1‐substituted phenyl‐1H‐1,2,3‐triazol‐4‐yl)methoxy)phenyl)‐1H‐pyrazol‐4‐yl)methylene)thiazolidine‐2,4‐diones 10 a‐n were designed, synthesized, and characterized by ¹H NMR, ¹³C NMR, IR, and ESI‐MS techniques. These compounds synthesized from appropriate reaction procedures with better yields. All the novel synthesized compounds 10a‐n were evaluated for their cytotoxic activity against the MCF‐7 cell line (Human breast cancer cell line) at different concentrations of 0.625, 1.25, 2.5, 5, and 10 μM, respectively. The cytotoxic evaluation assay is presented in terms of IC₅₀ values and percentage cell viability reduction compared against standard drug cisplatin. Among all novel synthesized compounds 10a‐n , some of the representative analogues particularly 10g and 10e exhibit remarkable cytotoxic activity with IC₅₀ values 0.454 and 0.586 μM, comparable to that of the standard drug cisplatin, and some analogues 10d , 10f , 10k, and 10m also have shown significant activity.     

姜黄素桥连卟啉光敏剂的合成及表征

为了开发新的高效光动力治疗光敏剂, 以2-(2-羟基萘基)-5,10,15,20-四苯基卟啉及其Cu(Ⅱ), Ni(Ⅱ), Zn(Ⅱ)配合物为原料, 利用1,6-二溴己烷桥连具有抗癌活性的小分子姜黄素, 设计合成4个新型的天然产物桥连卟啉化合物. 通过UV, ¹H NMR, IR, MS及元素分析等手段对该新型光敏药剂进行了结构表征; 在此基础上, 采用凝胶电泳法考察了化合物在光照和无光照条件下对pBR322质粒DNA的切割能力. 作为潜在光敏剂与DNA相互作用的初步研究表明, 其与DNA结合能力较强, 具有明显的光敏切割效果.     

Stable Anticancer Gold(III)–Porphyrin Complexes: Effects of Porphyrin Structure

In the design of physiologically stable anticancer gold(III) complexes, we have employed strongly chelating porphyrinato ligands to stabilize a gold(III) ion [Chem. Commun. 2003 , 1718; Coord. Chem. Rev. 2009 , 253, 1682]. In this work, a family of gold(III) tetraarylporphyrins with porphyrinato ligands containing different peripheral substituents on the meso‐aryl rings were prepared, and these complexes were used to study the structure–bioactivity relationship. The cytotoxic IC₅₀ values of [Au(Por)]⁺ (Por=porphyrinato ligand), which range from 0.033 to >100 μM , correlate with their lipophilicity and cellular uptake. Some of them induce apoptosis and display preferential cytotoxicity toward cancer cells than to normal noncancerous cells. A new gold(III)–porphyrin with saccharide conjugation [Au(4‐glucosyl‐TPP)]Cl ( 2 a ; H₂(4‐glucosyl‐TPP)=meso‐tetrakis(4‐β‐D ‐glucosylphenyl)porphyrin) exhibits significant cytostatic activity to cancer cells (IC₅₀=1.2–9.0 μM ) without causing cell death and is much less toxic to lung fibroblast cells (IC₅₀>100 μM ). The gold(III)–porphyrin complexes induce S‐phase cell‐cycle arrest of cancer cells as indicated by flow cytometric analysis, suggesting that the anticancer activity may be, in part, due to termination of DNA replication. The gold(III)–porphyrin complexes can bind to DNA in vitro with binding constants in the range of 4.9×10⁵ to 4.1×10⁶ dm³ mol^?1 as determined by absorption titration. Complexes 2 a and [Au(TMPyP)]Cl₅ ( 4 a ; [H₂TMPyP]⁴⁺=meso‐tetrakis(N‐methylpyridinium‐4‐yl)porphyrin) interact with DNA in a manner similar to the DNA intercalator ethidium bromide as revealed by gel mobility shift assays and viscosity measurements. Both of them also inhibited the topoisomerase I induced relaxation of supercoiled DNA. Complex 4 a , a gold(III) derivative of the known G‐quadruplex‐interactive porphyrin [H₂TMPyP]⁴⁺, can similarly inhibit the amplification of a DNA substrate containing G‐quadruplex structures in a polymerase chain reaction stop assay. In contrast to these reported complexes, complex 2 a and the parental gold(III)–porphyrin 1 a do not display a significant inhibitory effect (<10 %) on telomerase. Based on the results of protein expression analysis and computational docking experiments, the anti‐apoptotic bcl‐2 protein is a potential target for those gold(III)–porphyrin complexes with apoptosis‐inducing properties. Complex 2 a also displays prominent anti‐angiogenic properties in vitro. Taken together, the enhanced stabilization of the gold(III) ion and the ease of structural modification render porphyrins an attractive ligand system in the development of physiologically stable gold(III) complexes with anticancer and anti‐angiogenic activities.     

Benzoporphyrins and Acetylene-Substituted Porphyrins as Improved Photosensitizers in the Photodynamic Tumor Therapy with Porphyrin Platinum Conjugates

Summary.  A combination of a cisplatinum-like fragment and a porphyrin in the same molecule should not only result in the additivity of the dark toxicity of the platinum fragment and the phototoxicity of the porphyrin moiety, but also in the enrichment of the porphyrin platinum conjugates in tumor tissue, which cisplatinum alone does not show. To increase the penetration depth of the red light used in the photodynamic tumor therapy the conjugated system of the porphyrin components in porphyrin platinum conjugates had to be expanded. Sixteen new (NH₃)₂Pt derivatives of benzoporphyrins and acetylene-substituted porphyrins were synthesized, characterized, and tested with respect to their antitumor activity on the mammary carcinoma cell line MDA-MB-231. Received November 12, 2001. Accepted November 20, 2001     

Synthesis of Novel Porphyrin Derivatives and Their Cytotoxic Activities against A431 Cells

Three novel porphyrins, including two Schiff‐bases porphyrins, 5,10,15‐triphenyl‐20‐[4‐(2‐(4‐formyl)phenoxy)ethoxy]phenyl porphyrin ( H₂Pp ( 1 )), 5,10,15‐triphenyl‐20‐[4‐(2‐(4‐hydroxyimino)phenoxy)ethoxy]phenyl porphyrin ( H₂Pp ( 2 )) and 5,10,15‐triphenyl‐20‐[4‐(2‐(4‐m‐hydroxyanilinodeneformyl)phenoxy)ethoxy]phenyl porphyrin ( H₂Pp ( 3 )), as well as three metalloporphyrins ( CuPp ( 1a ), ZnPp ( 1b ), and CoPp ( 1c )) of porphyrin H₂Pp ( 1 ) were synthesized. Their molecular structures were characterized by ¹H‐NMR, MS, UV/VIS, and FT‐IR spectra. Furthermore, they were evaluated by their cytotoxicities against human epidermal squamous cell carcinoma cell (A431) and normal human horn cells (HaCaT) in vitro with MTT assay. Interestingly, these porphyrins and metalloporphyrins, which had a negligible cytotoxicity to HaCaT cells, showed highly cytotoxicity against A431 cells with IC₅₀ values in the range of 6.6–9.8 μM , and metalloporphyrins exhibited higher cytotoxicity than that of metal‐free porphyrins.     

Imine‐N‐Heterocyclic Carbenes as Versatile Ligands in Ruthenium(II) p‐Cymene Anticancer Complexes: A Structure–Activity Relationship Study

A family of novel imine‐N‐heterocyclic carbene ruthenium(II) complexes of the general formula [(η⁶‐p‐cymene)Ru(C^N)Cl]PF₆⁻ (where C^N is an imine‐N‐heterocyclic carbene chelating ligand with varying substituents) have been prepared and characterized. In this imine‐N‐heterocyclic carbene chelating ligand framework, there are three potential sites that can be modified, which distinguishes this class of ligand and provides a body of flexibilities and opportunities to tune the cytotoxicity of these ruthenium(II) complexes. The influence of substituent effects of three tunable domains on the anticancer activity and catalytic ability in converting coenzyme NADH to NAD⁺ is investigated. This family of complexes displays an exceedingly distinct anticancer activity against A549 cancer cells, despite their close structural similarity. Complex 9 shows the highest anticancer activity in this series against A549 cancer cells (IC₅₀=14.36 μm ), with an approximately 1.5‐fold better activity than the clinical platinum drug cisplatin (IC₅₀=21.30 μm ) in A549 cancer cells. Mechanistic studies reveal that complex 9 mediates cell death mainly through cell stress, including cell cycle arrest, inducing apoptosis, increasing intracellular reactive oxygen species (ROS) levels, and depolarization of the mitochondrial membrane potential (MMP). Furthermore, lysosomal damage is also detected by confocal microscopy.     

Enhanced Photodynamic Therapy by Reduced Levels of Intracellular Glutathione Obtained By Employing a Nano‐MOF with CuII as the Active Center

In photodynamic therapy (PDT), the level of reactive oxygen species (ROS) produced in the cell directly determines the therapeutic effect. Improvement in ROS concentration can be realized by reducing the glutathione (GSH) level or increasing the amount of photosensitizer. However, excessive amounts photosensitizer may cause side effects. Therefore, the development of photosensitizers that reduce GSH levels through synergistically improving ROS concentration in order to strengthen the efficacy of PDT for tumor is important. We report a nano‐metal–organic framework (Cu^II‐metalated nano‐MOF {CuL‐[AlOH]₂}_n (MOF‐2, H₆L=mesotetrakis(4‐carboxylphenyl)porphyrin)) based on Cu^II as the active center for PDT. This MOF‐2 is readily taken up by breast cancer cells, and high levels of ROS are generated under light irradiation. Meanwhile, intracellular GSH is considerably decreased owing to absorption on MOF‐2; this synergistically increases ROS concentration and accelerates apoptosis, thereby enhancing the effect of PDT. Notably, based on the direct adsorption of GSH, MOF‐2 showed a comparable effect with the commercial antitumor drug camptothecin in a mouse breast cancer model. This work provides strong evidence for MOF‐2 as a promising new PDT candidate and anticancer drug.     

Opp‐Dibenzoporphyrins as a Light‐Harvester for Dye‐Sensitized Solar Cells

New opp‐dibenzoporphyrins were prepared in a concise method that was based on a Pd⁰‐catalyzed cascade reaction. These porphyrins, which contained carboxylic‐acid linker groups on benzene rings that were fused to the porphyrin at their β,β′‐positions, were examined as sensitizers for dye‐sensitized solar cells for the first time. Whereas all of the porphyrins showed solar‐energy‐to‐electricity conversion, an opp‐dibenzoporphyrin with conjugated carboxylic‐acid linkers displayed the highest conversion efficiency and an exceptionally high J_sc value. Cyclic voltammetry of these porphyrins suggested that the fusion of two aromatic benzene rings onto the periphery of the porphyrin lowered the HOMO–LUMO energy gap; the incorporation of a conjugated carboxylic‐acid linker group decreased the HOMO–LUMO gap even further. These CV data are consistent with DFT calculations for these porphyrins and agree well with the UV/Vis absorption‐ and fluorescence spectra of these porphyrins.     

pH‐sensitive liposome retaining Fe‐porphyrin as SOD mimic for novel anticancer drug delivery system

In this article the novel design of an anticancer drug delivery system is reported based on a pH‐sensitive liposome retaining the Fe‐porphyrin as a superoxide dismutase(SOD) mimic. The liposomes contained cationic/anionic lipid combinations and were composed of Fe‐porphyrin, L ‐α‐phosphatidylcholine (DMPC), dimethylditetradecylammonium bromide (DTDAB), sodispdum oleate (OA_Na), and Tween‐80. The size of the liposome was approximately 30 nm. The EC₅₀ value (the effective concentration of compound required to produce a 50% lethal dose against cells) of the liposome was found to be significantly smaller than that of cisplatin as the control drug, suggesting that the liposome showed a high cytotoxicity toward the cancer cells. This is due to the fact that the pH‐sensitive liposome rapidly corresponds to the acidic environments of the endosomes and is unstable, and the Fe‐porphyrin is delivered into the cytosol. This result suggests that O may be useful as a target molecule to induce the selective death of cancer cells and that a pH‐sensitive liposome retaining Fe‐porphyrin as an SOD mimic is a new class of anticancer agent. Copyright © 2006 John Wiley & Sons, Ltd.     

Photodynamic Therapy of Oligoethylene Glycol‐Dendronized Reduction‐Sensitive Porphyrins

Graphene oxide (GO ) and its functionalized derivatives have attracted increasing attention in medical treatment. Herein, a reduction sensitive PEI‐GO ‐SS ‐TPP was synthesized for photodynamic therapy. More than 80% porphyrin release was observed in the presence of 10 mmol•L⁻¹ DTT in one day. The confocal laser scanning microscopy confirmed that the cell uptake efficiency of PEI‐GO‐SS‐TPP was remarkably enhanced as compared to free porphyrin which was significantly dependent on incubation time. For photodynamic therapy, GSH‐OEt could effectively increase the photodynamic therapy efficiency of PEI‐GO ‐SS ‐TPP . Compared with free porphyrin, the toxicity from PEI‐GO ‐SS ‐TPP is much higher with a low IC₅₀ (2.1 µg/mL ) value. All results indicate that the PEI‐GO ‐SS ‐TPP PSs are promising for photodynamic therapy.     

Highly Efficient,Conjugated‐Polymer‐Based Nano‐Photosensitizers for Selectively Targeted Two‐Photon Photodynamic Therapy and Imaging of Cancer Cells

Two‐photon photodynamic therapy (2P‐PDT) is a promising noninvasive treatment of cancers and other diseases with three‐dimensional selectivity and deep penetration. However, clinical applications of 2P‐PDT are limited by small two‐photon absorption (TPA) cross sections of traditional photosensitizers. The development of folate receptor targeted nano‐photosensitizers based on conjugated polymers is described. In these nano‐photosensitizers, poly{9,9‐bis[6′′‐(bromohexyl)fluorene‐2,7‐ylenevinylene]‐co‐alt‐1,4‐(2,5‐dicyanophenylene)}, which is a conjugated polymer with a large TPA cross section, acts as a two‐photon light‐harvesting material to significantly enhance the two‐photon properties of the doped photosensitizer tetraphenylporphyrin (TPP) through energy transfer. These nanoparticles displayed up to 1020‐fold enhancement in two‐photon excitation emission and about 870‐fold enhancement in the two‐photon‐induced singlet oxygen generation capability of TPP. Surface‐functionalized folic acid groups make these nanoparticles highly selective in targeting and killing KB cancer cells over NIH/3T3 normal cells. The 2P‐PDT activity of these nanoparticles was significantly improved, potentially up to about 1000 times, as implied by the enhancement factors of two‐photon excitation emission and singlet oxygen generation. These nanoparticles could act as novel two‐photon nano‐photosensitizers with combined advantages of low dark cytotoxicity, targeted 2P‐PDT with high selectivity, and simultaneous two‐photon fluorescence imaging capability; these are all required for ideal two‐photon photosensitizers.     

Design,synthesis, anticancer activity,and in silico studies of novel imidazo[1,2-a]pyridine based 1H-1,2,3-triazole derivatives

A novel series of imidazo[1,2-a]pyridine based 1H-1,2,3-triazole derivatives were designed, synthesized, and evaluated for their anticancer activity against two different human cancer cell lines. Most of the synthesized compounds displayed anticancer activity with IC₅₀ values from 2.35 to 120.46 μM. Furthermore, compounds 9b , 9c, 9d, 9f , and 9j showed potent inhibitory activity against cancer cell lines, with IC₅₀ values close to that of standard drug. It is important to note that compound 9d was more potent than the standard drug cisplatin with IC₅₀ values of 10.89 and 2.35 μM against Hela cell line and MCF-7 cell line, respectively.     

Diazido Mixed‐Amine Platinum(IV) Anticancer Complexes Activatable by Visible‐Light Form Novel DNA Adducts

Platinum diam(m)ine complexes, such as cisplatin, are successful anticancer drugs, but suffer from problems of resistance and side‐effects. Photoactivatable Pt^IV prodrugs offer the potential of targeted drug release and new mechanisms of action. We report the synthesis, X‐ray crystallographic and spectroscopic properties of photoactivatable diazido complexes trans,trans,trans‐[Pt(N₃)₂(OH)₂(MA)(Py)] ( 1 ; MA=methylamine, Py=pyridine) and trans,trans,trans‐[Pt(N₃)₂(OH)₂(MA)(Tz)] ( 2 ; Tz=thiazole), and interpret their photophysical properties by TD‐DFT modelling. The orientation of the azido groups is highly dependent on H bonding and crystal packing, as shown by polymorphs 1 p and 1 q . Complexes 1 and 2 are stable in the dark towards hydrolysis and glutathione reduction, but undergo rapid photoreduction with UVA or blue light with minimal amine photodissociation. They are over an order of magnitude more potent towards HaCaT keratinocytes, A2780 ovarian, and OE19 oesophageal carcinoma cells than cisplatin and show particular potency towards cisplatin‐resistant human ovarian cancer cells (A2780cis). Analysis of binding to calf‐thymus (CT), plasmids, oligonucleotide DNA and individual nucleotides reveals that photoactivated 1 and 2 form both mono‐ and bifunctional DNA lesions, with preference for G and C, similar to transplatin, but with significantly larger unwinding angles and a higher percentage of interstrand cross‐links, with evidence for DNA strand cross‐linking further supported by a comet assay. DNA lesions of 1 and 2 on a 50 bp duplex were not recognised by HMGB1 protein, in contrast to cisplatin‐type lesions. The photo‐induced platination reactions of DNA by 1 and 2 show similarities with the products of the dark reactions of the Pt^II compounds trans‐[PtCl₂(MA)(Py)] ( 5 ) and trans‐[PtCl₂(MA)(Tz)] ( 6 ). Following photoactivation, complex 2 reacted most rapidly with CT DNA, followed by 1 , whereas the dark reactions of 5 and 6 with DNA were comparatively slow. Complexes 1 and 2 can therefore give rapid potent photocytotoxicity and novel DNA lesions in cancer cells, with no activity in the absence of irradiation.     

Rational Design of Emissive NIR‐Absorbing Chromophores: RhIII Porphyrin‐Aza‐BODIPY Conjugates with Orthogonal Metal–Carbon Bonds

The facile synthesis of Group 9 Rh^III porphyrin‐aza‐BODIPY conjugates that are linked through an orthogonal Rh?C(aryl) bond is reported. The conjugates combine the advantages of the near‐IR (NIR) absorption and intense fluorescence of aza‐BODIPY dyes with the long‐lived triplet states of transition metal rhodium porphyrins. Only one emission peak centered at about 720 nm is observed, irrespective of the excitation wavelength, demonstrating that the conjugates act as unique molecules rather than as dyads. The generation of a locally excited (LE) state with intramolecular charge‐transfer (ICT) character has been demonstrated by solvatochromic effects in the photophysical properties, singlet oxygen quantum yields in polar solvents, and by the results of density functional theory (DFT) calculations. In nonpolar solvents, the Rh^III conjugates exhibit strong aza‐BODIPY‐centered fluorescence at around 720 nm (Φ_F=17–34 %), and negligible singlet oxygen generation. In polar solvents, enhancements of the singlet‐oxygen quantum yield (Φ_Δ=19–27 %, λ_ex=690 nm) have been observed. Nanosecond pulsed time‐resolved absorption spectroscopy confirms that relatively long‐lived triplet excited states are formed. The synthetic methodology outlined herein provides a useful strategy for the assembly of functional materials that are highly desirable for a wide range of applications in material science and biomedical fields.     

Synthesis of chloro,fluoro, and nitro derivatives of 7‐amino‐5‐aryl‐6‐cyano‐5H‐pyrano pyrimidin‐2,4‐diones using organic catalysts and their antimicrobial and anticancer activities

Chloro, fluoro, and nitro derivatives of 7‐amino‐5‐aryl‐6‐cyano‐5H‐pyrano pyrimidin‐2,4‐diones were produced by reacting malononitrile, barbituric acid, and aromatic aldehydes together with a DABCO catalyst in an aqueous one‐pot reaction. This is the first report of these compounds being synthesized with DABCO as a catalyst, which produced the compounds in yields in excess of 90%. The 2,4‐difluoro derivative ( 11 ) was novel. The structures of the synthesized compounds were elucidated by means of ¹H, ¹³C, and 2D NMR spectroscopy. Compound 2 (2‐Cl derivative) had MBC values of <200μM against both Staphylococcus aureus and MRSA, and the 2‐nitro derivative 5 had an MBC of 191μM against the Gram–ve Escherichia coli. The synthesized compounds were also tested for their anticancer activity against a HeLa cell line, where all the compounds showed better activity (IC₅₀ values between 129μM and 340μM) than 5‐fluorouracil, a commonly known anticancer drug.