Pt(II) Tetrafacial Barrel with Aggregation-Induced Emission for Sensing.

A new tetraphenylpyrazine-based tetraimidazole ligand (L) was synthesized and used for subcomponent self-assembly with cis-(tmeda)Pd(NO3)2 and cis-Pt(PEt3)2(OTf)2, leading to the formation of two tetrafacial barrels [Pd8L4(tmeda)8](NO3)16 (1) and [Pt8L4(PEt3)16](OTf)16 (2), respectively. Although ligand L is aggregation-induced emission (AIE) active, barrel 2 showed a magnificently higher AIE activity than ligand L, while 1 failed to retain the AIE properties of the ligand. Pd(II) barrel 1, undergoing an aggregation-caused quenching (ACQ) phenomenon, nullified the AIE activity of the ligand to be used in the photophysical application. The enhanced emission in the aggregated state of Pt(II) barrel 2 was used for the recognition of picric acid (PA), which is explosive in nature and one of the groundwater contaminants in landmine areas. The recognition of picric acid was found to be selective in comparison with that of other nitroaromatic compounds (NACs), which could be attributed to ground-state complex formation and resonance energy transfer between picric acid and barrel 2. The use of new AIE-active assembly 2 for selective detection of PA with a low detection limit is noteworthy.

Selective separation of planar and non-planar hydrocarbons using an aqueous Pd6 interlocked cage.

Polycyclic aromatic hydrocarbons (PAHs) find multiple applications ranging from fabric dyes to optoelectronic materials. Hydrogenation of PAHs is often employed for their purification or derivatization. However, separation of PAHs from their hydrogenated analogues is challenging because of their similar physical properties. An example of such is the separation of 9,10-dihydroanthracene from phenanthrene/anthracene which requires fractional distillation at high temperature (∼340 °C) to obtain pure anthracene/phenanthrene in coal industry. Herein we demonstrate a new approach for this separation at room temperature using a water-soluble interlocked cage (1) as extracting agent by host-guest chemistry. The cage was obtained by self-assembly of a triimidazole donor L·HNO3 with cis-[(tmeda)Pd(NO3)2] (M) [tmeda = N,N,N',N'-tetramethylethane-1,2-diamine]. 1 has a triply interlocked structure with an inner cavity capable of selectively binding planar aromatic guests.

Shifting the Triangle-Square Equilibrium of Self-Assembled Metallocycles by Guest Binding with Enhanced Photosensitization.

Shifting a triangle-square equilibrium in one direction is an important problem in supramolecular self-assembly. Reaction of a benzothiadiazole-based diimidazole donor with a cis-Pt(II) acceptor yielded an equilibrium mixture of a triangle ([C18H24N10O6S1Pt1]3≡ PtMCT) and a square ([C18H24N10O6S1Pt1]4≡ PtMCS). We report here the shifting of such equilibrium toward a triangle using a guest (pyrene aldehyde, G1). While both benzothiadiazole and pyrene aldehyde can form reactive oxygen species (ROS) in organic solvents, their therapeutic use in water is restricted due to aqueous insolubility. The enhanced water solubility of the benzothiadiazole unit and G1 by macrocycle formation and host-guest complexation, respectively, enabled enhanced ROS generation by the host-guest complex (G1' ⊂ PtMCT) in water (G1' = hydrated form of G1). The guest-encapsulated metallacycle (G1' ⊂ PtMCT) has shown synergistic antibacterial activity compared to the mixture of macrocycles upon white-light irradiation due to enhanced ROS generation. The mechanism for such enhanced activity was established by measuring the oxidative stress and relative internalization of PtMCs and G1' ⊂ PtMCT.

Molecular Cavity for Catalysis and Formation of Metal Nanoparticles for Use in Catalysis.

The employment of weak intermolecular interactions in supramolecular chemistry offers an alternative approach to project artificial chemical environments like the active sites of enzymes. Discrete molecular architectures with defined shapes and geometries have become a revolutionary field of research in recent years because of their intrinsic porosity and ease of synthesis using dynamic non-covalent/covalent interactions. Several porous molecular cages have been constructed from simple building blocks by self-assembly, which undergoes many self-correction processes to form the final architecture. These supramolecular systems have been developed to demonstrate numerous applications, such as guest stabilization, drug delivery, catalysis, smart materials, and many other related fields. In this respect, catalysis in confined nanospaces using such supramolecular cages has seen significant growth over the years. These porous discrete cages contain suitable apertures for easy intake of substrates and smooth release of products to exhibit exceptional catalytic efficacy. This review highlights recent advancements in catalytic activity influenced by the nanocavities of hydrogen-bonded cages, metal-ligand coordination cages, and dynamic or reversible covalently bonded organic cages in different solvent media. Synthetic strategies for these three types of supramolecular systems are discussed briefly and follow similar and simplistic approaches manifested by simple starting materials and benign conditions. These examples demonstrate the progress of various functionalized molecular cages for specific chemical transformations in aqueous and nonaqueous media. Finally, we discuss the enduring challenges related to porous cage compounds that need to be overcome for further developments in this field of work.

Self-assembled metallasupramolecular cages towards light harvesting systems for oxidative cyclization.

Designing artificial light harvesting systems with the ability to utilize the output energy for fruitful application in aqueous medium is an intriguing topic for the development of clean and sustainable energy. We report here facile synthesis of three prismatic molecular cages as imminent supramolecular optoelectronic materials via two-component coordination-driven self-assembly of a new tetra-imidazole donor (L) in combination with 180°/120° di-platinum(ii) acceptors. Self-assembly of 180° trans-Pt(ii) acceptors A1 and A2 with L leads to the formation of cages Pt4 L 2(1a) and Pt8 L 2(2a) respectively, while 120°-Pt(ii) acceptor A3 with L gives the Pt8 L 2(3a) metallacage. PF6 - analogues (1b, 2b and 3b) of the metallacages possess a high molar extinction coefficient and large Stokes shift. 1b-3b are weakly emissive in dilute solution but showed aggregation induced emission (AIE) in a water/MeCN mixture as well as in the solid state. AIE active 2b and 3b in aqueous (90% water/MeCN mixture) medium act as donors for fabricating artificial light harvesting systems via Förster resonance energy transfer (FRET) with organic dye rhodamine-B (RhB) with high energy efficiency and good antenna effect. The metallacages 2b and 3b represent an interesting platform to fabricate new generation supramolecular aqueous light harvesting systems with high antenna effect. Finally, the harvested energy of the LHSs (2b + RhB) and (3b + RhB) was utilized successfully for efficient visible light induced photo-oxidative cross coupling cyclization of N,N-dimethylaniline (4) with a series of N-alkyl/aryl maleimides (5) in aqueous acetonitrile with dramatic enhancement in yields compared to the reactions with RhB or cages alone.

BODIPY-linked cis-dichlorido zinc(ii) conjugates: the strategic design of organelle-specific next-generation theranostic photosensitizers.

Dipicolylamine (dpa) based cis-dichlorido zinc(ii) complexes [Zn(L1-3)Cl2] (1-3), where L2 and L3 are non-iodo and di-iodo BODIPY-appended dpa in 2 and 3, and L1 is dpa in control complex 1, were prepared and characterized and their photocytotoxicity was studied. Complexes 2 and 3 were developed as potential substitutes for zinc(ii)-porphyrins/phthalocyanines that are photodynamic therapeutic agents with moderate activity owing to their inherent hydrophobicity and aggregation-induced deactivation mechanism. In our approach, we strategically designed hybrid inorganic-organic zinc-BODIPY conjugates as theranostic photosensitizers. The structurally characterized diamagnetic Zn(ii) cis-dichlorido complexes mimic cisplatin and serve as new-generation photosensitizers with enhanced aqueous solubility and mito-DNA targeting propensity while imparting significant physiological stability to the heavy atom tethered BODIPY ligand, L3. The BODIPY complexes showed a visible band near 500 nm (ε∼ 34 000-44 000 dm3 mol-1 cm-1) and an emission band at 507 nm for 2 in 1% DMSO-Dulbecco's phosphate buffered saline. The labile chlorido ligands (ΛM∼ 200 S m2 mol-1 in 9 : 1 H2O-DMSO) generated positively charged complexes inside the cellular medium enabling them to cross the mitochondrial membrane for this organelle-selective localization and singlet oxygen-mediated apoptotic photocytotoxicity at nanomolar concentrations for 3 in HeLa and MCF-7 cells in light (400-700 nm), while being less active in the dark.

Structurally Characterized BODIPY-Appended Oxidovanadium(IV) ß-Diketonates for Mitochondria-Targeted Photocytotoxicity.

Mixed-ligand oxidovanadium(IV) ß-diketonates having NNN-donor dipicolylamine-conjugated to boron-dipyrromethene (BODIPY in L1) and diiodo-BODIPY (in L2) moieties, namely, [VO(L1)(acac)]Cl (1), [VO(L2)(acac)]Cl (2), and [VO(L1)(dbm)]Cl (3), where acac and dbm are monoanionic O,O-donor acetylacetone and 1,3-diphenyl-1,3-propanedione, were prepared, characterized, and tested for their photoinduced anticancer activity in visible light. Complexes 1 and 2 were structurally characterized as their PF6 - salts (1a and 2a) by X-ray crystallography. They showed VIVN3O3 six-coordinate geometry with dipicolylamine base as the facial ligand. The non-iodinated BODIPY complexes displayed absorption maxima at ∼501 nm, while it is ∼535 nm for the di-iodinated 2 in 10% DMSO-PBS buffer medium (pH = 7.2). Complexes 1 and 3 being green emissive (λem, ∼512 nm; λex, 470 nm; ΦF, ∼0.10) in 10% aqueous DMSO were used for cellular imaging studies. Complex 3 localized primarily in the mitochondria of the cervical HeLa cells with a co-localization coefficient value of 0.7. The non-emissive diiodo-BODIPY complex 2 showed generation of singlet oxygen (ΦΔ ≈ 0.47) on light activation. Annexin-V assay showed singlet oxygen-mediated cellular apoptosis, making this complex a targeted PDT agent.

Chemistry of photoswitching molecules in the confined nanospace of aqueous molecular vessels.

Reversible photoswitching molecules have been developed as promising candidates for building effective molecular motors. In aqueous medium many of such photoswitching molecules become either insoluble or stable in a particular state to abolish their reversible nature. Hence, it is a challenging task to explore the chemistry of such photochromic molecules in aqueous medium. This Frontier article discusses the recent developments in understanding the behaviour of photoswitching molecules in the confined nanospace of aqueous molecular vessels.

Unusual Behavior of Donor-Acceptor Stenhouse Adducts in Confined Space of a Water-Soluble PdII8 Molecular Vessel.

Donor-acceptor Stenhouse adducts (DASA) are new-generation photochromic compounds discovered recently. DASA exist normally in open form (blue/violet) and readily convert to cyclic (light yellow/colorless) zwitterionic form reversibly in the presence of green light in toluene/dioxane. In aqueous medium, the open form is not stable and converts to the cyclic zwitterionic form irreversibly. We report here a new self-assembled Pd8 molecular vessel (MV) that can stabilize and store the open form of DASA even in aqueous medium. Reaction of the 90° acceptor cis-(tmeda)Pd(NO3)2 (M) [tmeda = N, N, N', N'-tetramethylethane-1,2-diamine] with a symmetric tetraimidazole donor (L, 3,3',5,5'-tetra(1 H-imidazol-1-yl)-1,1'-biphenyl) in a 2:1 molar ratio yielded a water-soluble [8+4] self-assembled M8L4 molecular barrel (MV). This barrel (MV) is found to be a potential molecular vessel to store and stabilize the open forms of DASA in aqueous medium over the more stable zwitterionic cyclic form, while in the absence of the barrel the same DASA exist in cyclic zwitterionic form in aqueous medium. The hydrophobic interaction between the cavity and the open form of DASA molecules benefits reaching an out-of-equilibrium or reverse equilibrium state in aqueous medium. The presence of excess MV could even drive the conversion of the stable cyclic form to the open form in aqueous medium. The host-guest complex is stable upon irradiating with green light. To the best of our knowledge, this is the first successful attempt to stabilize the open form of DASA molecules in aqueous medium and the first report on the fate of DASA in a confined space discrete molecular architecture. Furthermore, the molecular vessel has been utilized for catalytic Michael addition reactions of a series of nitrostyrene derivatives with 1,3-indandione in aqueous medium.

Ruthenium(II) Metalla[2]catenanes and Macrocycles via Donor-Dependent Self-Assembly.

Donor-selective coordination-driven self-assembly of a bis(dipyrrin)-bridged new diruthenium acceptor (RuA) with dipyridyl and diimidazolyl donors has been reported. The self-assembly of the ruthenium(II) acceptor with imidazolyl donors resulted in the formation of either [2 + 2] self-assembled monomeric macrocycles (MMs) or a mixture of metalla[2]catenanes (MCs) and MMs depending on the solvents used. On the contrary, similar self-assembly with the pyridyl donors resulted in simple [2 + 2] macrocycles (MMs) exclusively, irrespective of the solvents used. The new ruthenium acceptor and self-assembled macrocycles were systematically characterized by multinuclear NMR and electrospray ionization mass spectrometry study. The structure of one of the metalla[2]catenanes (MC1) was further confirmed by single-crystal X-ray diffraction studies. Density functional theory calculations inferred that the interlocked structures with imidazolyl donors are stabilized by π-π interactions between the benzene rings, while such interactions cease to exist with the pyridyl linkers, leading to the formation of noninterlocked macrocycles.

Multifunctional Self-Assembled Macrocycles with Enhanced Emission and Reversible Photochromic Behavior.

A series of self-assembled functional Pt(II) molecular hexagons (M1-M3) is reported. Hexagons M1 and M2 were designed employing aggregation induced emissive and photochromic building blocks, respectively, while macrocycle M3 is a bifunctional, containing both the kinds of building units. Hexagons M1 and M3 were found to inherit the enhanced emission with aggregate formation which was explored using UV-vis and fluorescence spectroscopy. The enhanced emission of macrocycle M3 compared to that of its building units was driven both by metal-ligand coordination and formation of nanoaggregates as evident from SEM, DLS and TEM analyses. Two of the macrocycles (M2 and M3) were also found to be photochromic due to the presence of spiropyran in the molecular backbone. Due to the virtue of protonation-deprotonation equilibrium of the spiropyran, these macrocycles (M2 and M3) showed reversible acidochromic behavior. Macrocycle M3 represents the first example of a self-assembled Pt(II) architecture which is multifunctional with aggregation-induced emission (AIE), photochromic, and acidochromic properties. This new generation macrocycle (M3) also showed coordination-driven enhanced emission and light-induced color change behavior compared to the starting building blocks. Our present approach of incorporating multiple functions into a single self-assembled structure with enhanced functionality compared to the starting building blocks via coordination self-assembly is noteworthy and has huge potential for the development of multifunctional materials.

Self-Assembled PdII6 Molecular Spheroids and Their Proton Conduction Property.

A series of molecular spheroids (SP1-SP4) was synthesized using pseudolinear bisimidazole and bisbenzimidazole donors in combination with Pd(NO3)2 acceptor via coordination-driven self-assembly. They were characterized by NMR and mass spectrometry, and the solid-state structures of SP1 and SP3 were confirmed by X-ray diffraction. Crystal packing revealed the presence of molecular channels with water molecules in the channels as proton source. All the systems showed proton conductivity across a wide range of temperature and relative humidity. Furthermore, the mode of proton conduction in these molecular spheroids was explored by performing a control experiment using 2,4-dinitrophenol molecule, which indicates that the proton conductivity in the present case increases with increasing surface area of these molecular spheroids.

Mitochondria-localizing BODIPY-copper(ii) conjugates for cellular imaging and photo-activated cytotoxicity forming singlet oxygen.

Copper(ii) acetylacetonates of N,N,N-donor dipicolylamine (dpa) ligands, viz. [Cu(L1)(acac)]ClO4 (1), [Cu(L2)(acac)]ClO4 (2) and [Cu(L3)(acac)]ClO4 (3), where L1 is benzyldipicolylamine (bzdpa), L2 and L3 are non-iodinated and diiodinated BODIPY (borondipyrromethene) ligands and Hacac is acetylacetone, were synthesized and characterized and their photocytotoxicity was studied. The BODIPY complex 2, structurally characterized by X-ray crystallography, has copper(ii) in a distorted square-pyramidal geometry (degree of trigonality, τ5 = 0.28). The one-electron paramagnetic and redox active copper(ii) complexes displayed 1 : 1 electrolytic behaviour in polar organic solvents. The BODIPY complexes 2 and 3 showed respective visible bands at 498 and 539 nm in 5% DMSO-phosphate buffered saline (PBS). Complex 2 displayed an emission band at 511 nm in 5% DMSO-PBS (λex = 465 nm) with a fluorescence quantum yield (ΦF) value of 0.15. Cellular imaging using this complex showed significant mitochondrial localization in HeLa and MCF-7 cancer cells. Complex 3 with a diiodo-BODIPY moiety was non-emissive (ΦF = 0.01) but acted as an efficient photosensitizer with a singlet oxygen quantum yield value of 0.59 (ΦΔ). Complex 3 showed a remarkable PDT effect with apoptotic cell death due to singlet oxygen giving IC50 values within 0.04-0.06 µM in HeLa and MCF-7 cells using visible light (400-700 nm), while being less toxic in the dark.

Catalytic Intramolecular Cycloaddition Reactions by Using a Discrete Molecular Architecture.

A discrete tetragonal tube-shaped complex (MT-1) has been synthesised by coordination-driven self-assembly of a carbazole-based tetraimidazole donor L and a Pd(II) 90° acceptor, that is, [cis-(dppf)Pd(OTf)2 ] (dppf=diphenylphosphinoferrocene, OTf=CF3 SO3- ). Complex MT-1 was characterised by multinuclear NMR, ESI-MS and single-crystal X-ray diffraction analysis (SCXRD), which showed its symmetrical tetrafacial tube-shaped architecture possessing a large cavity described by four aromatic walls. This coordination cage was successfully utilised as a molecular vessel to perform intramolecular cycloaddition reactions of O-allylated benzylidinebarbituric acid derivatives inside its confined nanospace. The presence of a catalytic amount of MT-1 promoted [4+2] cycloaddition reactions in a regio- and stereoselective manner, yielding the corresponding penta/tetracyclouracil derivatives in good yields under mild reaction conditions. This protocol is interesting compared with the literature reports for the synthesis of similar chromenopyran pyrimidinedione derivatives under high-temperature reflux conditions or solid-state melt reactions (SSMRs).

Terpyridyl oxovanadium(IV) complexes for DNA crosslinking and mito-targeted photocytotoxicity.

Oxovanadium(IV) complexes [VO(L1/L2)Cl2]n+ (1,2) of (anthracenyl)terpyridine (An-tpy as L1 in 1, n=0) and triphenylphosphonium-appended (anthracenyl)terpyridine (An-tpy-TPP+ as L2 in 2, n=1) were synthesized, characterized and their DNA crosslinking ability, photocytotoxicity in visible light and cellular localization in cancer cells studied. The bromide derivative of 2, viz. [VO(An-tpy-TPP)Br2]Br (3) is structurally characterized. The structure showed trans disposition of two halides in the coordination sphere and the TPP+ unit is a pendant to the terpyridyl ligand. The DNA melting and comet assay studies on the complexes suggest the formation of DNA crosslinks. Complexes 1 and 2 displayed ~10 fold increase in cytotoxicity on exposure to visible light (400-700nm) when compared to those in dark in HeLa and MCF-7 cells. FACScan (Fluorescence Associated Cell Sorter Scan) analysis showed cellular apoptosis when treated with the complex in visible light in comparison to their dark controls. Fluorescence microscopic studies using complex 2 revealed its mitochondrial localization within the cancer cells.

Stepwise Construction of Self-Assembled Heterometallic Cages Showing High Proton Conductivity.

Two neutral tripodal metalloligands (CoL and FeL where L=C18 H21 N10 ) containing a clathrochelate core were synthesized and characterized in one-step. Reactions of these ligands with three different metal acceptors cis-(tmen)Pd(NO3 )2 (tmen = tetramethylethylenediamine), Zn(NO3 )2 and Mn(ClO4 )2 separately yielded a series of heterometallic coordination cages (1 a-3 a and 1 b-3 b) in high yields. Depending on the nature of coordination geometry of the acceptors, the resulting assemblies have trigonal- bipyramidal (1 a/1 b), open-cubic (2 a/2 b), and closed-cubic structures (3 a/3 b). The structures of the complexes 1 a, 2 a, 2 b, 3 a, and 3 b were confirmed by single-crystal X-ray diffraction studies. Analysis of crystal packing of the complexes 3 a and 3 b revealed the presence of several coordinated and lattice water molecules in the intermolecular channels. Both these complexes (3 a and 3 b) showed very high water adsorption under humid conditions. In addition, 3 a and 3 b exhibited promising proton conductivity of 3.31×10-3 and 1.05×10-4  S cm-1 at 70 °C under 98 % relative humidity (RH) respectively, with activation energy of 1.00-0.78 eV.

Versatility of Two Diimidazole Building Blocks in Coordination-Driven Self-Assembly.

A series of discrete molecular architectures was synthesized via self-assembly of two "linear" diimidazole donors [L1 = 1,4-di(1H-imidazol-1-yl)benzene and L2 = 1,1'-(2,5-dimethyl-1,4-phenylene)bis(1H-imidazole)] independently with cis-[(tmeda)Pd(NO3)2] [tmeda = N,N,N',N'-tetramethylethane-1,2-diamine], cis-[(tmeda)Pt(NO3)2], a diplatinum(II) acceptor (bisPt), and Pd(NO3)2. The donors L1 and L2 are isostructural with four hydrogens in the benzene ring of L1, whereas in L2 two of such hydrogens are substituted by methyl groups. The assemblies were characterized by NMR spectroscopy and electrospray ionization mass spectrometry analyses along with single-crystal structure determination of three of them. While the self-assembly of L1 with cis-[(tmeda)Pd(NO3)2] solely formed a [3 + 3] self-assembled molecular triangle (1), L2 with the same acceptor predominantly resulted in the formation of a [4 + 4] molecular square (3). Such a dramatic change in the final outcome in the coordination-driven self-assembly by simple alkyl substitution of isostructural donors is remarkable. Interestingly, self-assembly of L1 and L2 with analogous Pt(II) acceptor cis-[(tmeda)Pt(NO3)2] yielded mixtures of [3 + 3] triangle and [4 + 4] square, where the molecular triangles (4 and 6) were the predominant products in both the cases. The same donors in combination with a 0° acceptor bisPt independently formed the expected [2 + 2] metallo-macrocycles (8 and 9). Surprisingly, the macrocycle (9) involving L2 is found to exist in more than one conformation at room temperature. Moreover, the diimidazole donors formed unprecedented Pd6L12 molecular spheres (10 and 11) when they were separately treated with Pd(NO3)2. The imidazole moieties in the ligands are found to appear in versatile orientations in the synthesized molecules due to their rotational flexibility to produce required bite angles for the particular architecture.

Self-assembly of Metallamacrocycles Employing a New Benzil-based Organometallic Bisplatinum(II) Acceptor.

A benzil-based semi-rigid dinuclear-organometallic acceptor 4,4'-bis[trans-Pt(PEt(3))(2)(NO(3))(ethynyl)]benzil (bisPt-NO(3)) containing a Pt-ethynyl functionality was synthesized in good yield and characterized by multinuclear NMR ((1)H, (31)P, and (13)C), electrospray ionization mass spectrometry (ESI-MS), and single-crystal X-ray diffraction analysis of the iodide analogue bisPt-I. The stoichiometric (1:1) combination of the acceptor bisPt-NO(3) separately with four different ditopic donors (L(1)-L(4); L(1) = 9-ethyl-3,6-di(1H-imidazol-1-yl)-9H-carbazole, L(2) = 1,4-bis((1H-imidazol-1-yl)methyl)benzene, L(3) = 1,3-bis((1H-imidazol-1-yl)methyl)benzene and L(4) = 9,10-bis((1H-imidazol-1-yl) methyl)anthracene) yielded four [2 + 2] self-assembled metallacycles M(1)-M(4) in quantitative yields, respectively. All these newly synthesized assemblies were characterized by various spectroscopic techniques (NMR, IR, ESI-MS) and their sizes/shapes were predicted through geometry optimization employing the PM6 semi-empirical method. The benzil moiety was introduced in the backbone of the acceptor bisPt-NO(3) due to the interesting structural feature of long carbonyl C-C bond (∼1.54 Å), which enabled us to probe the role of conformational flexibility on size and shapes of the resulting coordination ensembles.