Supramolecular Polymers Self‐Assembled from trans‐Bis(pyridine) Dichloropalladium(II) and Platinum(II) Complexes

Two structurally similar trans‐bis(pyridine) dichloropalladium(II)‐ and platinum(II)‐type complexes were synthesized and characterized. They both self‐assemble in n‐hexane to form viscous fluids at lower concentrations, but form metallogels at sufficient concentrations. The viscous solutions were studied by capillary viscosity measurements and UV/Vis absorption spectra monitored during the disassembly process indicated that a metallophilic interaction was involved in the supramolecular polymerization process. For the two supramolecular assemblies, uncommon continuous porous networks were observed by using SEM and TEM revealed that they were built from nanofibers that fused and crosslinked with the increase of concentration. The xerogels of the palladium and platinum complexes were carefully studied by using synchrotron radiation WAXD and EXAFS. The WAXD data show close stacking distances driven by π–π and metal–metal interactions and an evident dimer structure for the platinum complex was found. The coordination bond lengths were extracted from fitting of the EXAFS data. Moreover, close Pt^II–Pt^II (Pd^II–Pd^II) and Pt?Cl (Pd?Cl) interactions proposed from DFT calculations in the reported oligo(phenylene ethynylene) (OPE)‐based palladium(II) pyridyl supramolecular polymers were also confirmed by using EXAFS. The Pt^II–Pt^II interaction is more feasible for supramolecular interaction than the Pd^II–Pd^II interaction in our simple case.     

The Energetic Significance of Metallophilic Interactions

Metallophilic interactions are increasingly recognized as playing an important role in molecular assembly, catalysis, and bio‐imaging. However, present knowledge of these interactions is largely derived from solid‐state structures and gas‐phase computational studies rather than quantitative experimental measurements. Here, we have experimentally quantified the role of aurophilic (Au^I???Au^I), platinophilic (Pt^II???Pt^II), palladophilic (Pd^II???Pd^II), and nickelophilic (Ni^II???Ni^II) interactions in self‐association and ligand‐exchange processes. All of these metallophilic interactions were found to be too weak to be well‐expressed in several solvents. Computational energy decomposition analyses supported the experimental finding that metallophilic interactions are overall weak, meaning that favorable dispersion and orbital hybridization contributions from M???M binding are largely outcompeted by electrostatic or dispersion interactions involving ligand or solvent molecules. This combined experimental and computational study provides a general understanding of metallophilic interactions and indicates that great care must be taken to avoid over‐attributing the energetic significance of metallophilic interactions.     

Self‐Assembly and (Hydro)gelation Triggered by Cooperative π–π and Unconventional CH⋅⋅⋅X Hydrogen Bonding Interactions

Weak C? H???X hydrogen bonds are important stabilizing forces in crystal engineering and anion recognition in solution. In contrast, their quantitative influence on the stabilization of supramolecular polymers or gels has thus far remained unexplored. Herein, we report an oligophenyleneethynylene (OPE)‐based amphiphilic Pt^II complex that forms supramolecular polymeric structures in aqueous and polar media driven by π–π and different weak C‐H???X (X=Cl, O) interactions involving chlorine atoms attached to the Pt^II centers as well as oxygen atoms and polarized methylene groups belonging to the peripheral glycol chains. A collection of experimental techniques (UV/Vis, 1D and 2D NMR, DLS, AFM, SEM, and X‐Ray diffraction) demonstrate that the interplay between different weak noncovalent interactions leads to the cooperative formation of self‐assembled structures of high aspect ratio and gels in which the molecular arrangement is maintained in the crystalline state.     

Construction of Discrete Pentanuclear Platinum(II) Stacks with Extended Metal–Metal Interactions by Using Phosphorescent Platinum(II) Tweezers

Discrete pentanuclear Pt^II stacks were prepared by the host‐guest adduct formation between multinuclear tweezer‐type Pt^II complexes. The formation of the Pt^II stacks in solution was accompanied by color changes and the turning on of near‐infrared emission resulting from Pt⋅⋅⋅Pt and π–π interactions. The X‐ray crystal structure revealed the formation of a discrete 1:1 adduct, in which a linear stack of five Pt^II centers with extended Pt⋅⋅⋅Pt interactions was observed. Additional binding affinity and stability have been achieved through a multinuclear host‐guest system. The binding behaviors can be fine‐tuned by varying the spacer between the two Pt^II moieties in the guests. This work provides important insights for the construction of discrete higher‐order supramolecular metal‐ligand aggregates using a tweezer‐directed approach.     

Recognition Properties and Self‐assembly of Planar [M(2‐pyridyl‐1,2,3‐triazole)2]2+ Metallo‐ligands

Molecular recognition continues to be an area of keen interest for supramolecular chemists. The investigated [M( L )₂]²⁺ metallo‐ligands (M=Pd^II, Pt^II, L =2‐(1‐(pyridine‐4‐methyl)‐1 H‐1,2,3‐triazol‐4‐yl)pyridine) form a planar cationic panel with vacant pyridyl binding sites. They interact with planar neutral aromatic guests through π–π and/or metallophilic interactions. In some cases, the metallo‐ligands also interacted in the solid state with Ag^I either through coordination to the pendant pyridyl arms, or through metal–metal interactions, forming coordination polymers. We have therefore developed a system that reliably recognises a planar electron‐rich guest in solution and in the solid state, and shows the potential to link the resultant host–guest adducts into extended solid‐state structures. The facile synthesis and ready functionalisation of 2‐pyridyl‐1,2,3‐triazole ligands through copper(I)‐catalyzed azide–alkyne cycloaddition (CuAAC) “click” chemistry should allow for ready tuning of the electronic properties of adducts formed from these systems.     

Mechano‐fluorochromic PtII Luminogen and Its Cysteine Recognition

A new triphenylamine‐based organometallic Pt^II luminogen ( 1 ) and its analogous organic compound ( 2 ) are reported. The molecules are decorated with aldehyde functionality to improve their photophysical properties by utilising donor–acceptor interactions. The single crystal X‐ray structure analysis of Pt^II analogue 1 revealed that the neighbouring molecules were loosely organised by weak intermolecular C?H???π interactions. Because of the twisted nature of the triphenylamine backbone the compounds showed aggregation‐induced emission enhancement in THF/water mixture. Due to their loose crystal packing, upon application of external stimuli these luminogens exhibited mechano‐fluorochromic behaviour. The crystalline forms of the compounds displayed a more superior emission efficiency than the grinded samples. Moreover, the compounds showed crystallization‐induced emission enhancement (CIEE) and exhibited chemodosimetric response towards cysteine under physiological condition.     

Mechanistic Insights into Statistical Co-Assembly of Metal Complexes

Statistical copolymerization plays a key role in many biological and technological processes; however, mechanistic understanding of the formation of analogous supramolecular counterparts remains limited. Herein, we report detailed insights into the supramolecular co-assembly of two π-conjugated Pd^II and Pt^II complexes, which in isolation self-assemble into flexible fibers and nanodisks, respectively. An efficient single-step co-assembly into only one type of nanostructure (fibers or nanodisks) takes place if any of the components is in excess. In contrast, equimolar mixtures lead to Pd^II-rich fiber-like co-assemblies by a statistical co-nucleation event along with a residual amount of self-sorted nanodisks in a stepwise manner.     

Through-Space Spin Coupling in a Silver(II) Porphyrin Dimer upon Stepwise Oxidations: AgII⋅⋅⋅AgII,AgII⋅⋅⋅AgIII,and AgIII⋅⋅⋅AgIII Metallophilic Interactions

Metallophilic interactions between closed-shell metal ions are becoming a popular tool for a variety of applications related to high-end materials. Heavier d⁸ transition-metal ions are also considered to have a closed shell and can be involved in such interactions. There is no systematic investigation so far to estimate the structure and energy characteristics of metallophilic interactions in Ag^II/Ag^II (d⁹/d⁹), Ag^III/Ag^III (d⁸/d⁸), and mixed-valent Ag^II/Ag^III (d⁹/d⁸) complexes, which have been demonstrated in the present study. Both interporphyrinic and intermetallic interactions were investigated on stepwise oxidation by using a rigid ethene-bridged cis silver(II) porphyrin dimer and the results compared with those for highly flexible ethane-bridged analogues. By controlling the nature of chemical oxidants and their stoichiometry, both 1e and 2e oxidations were done stepwise to generate Ag^II/Ag^III mixed-valent and Ag^III/Ag^III porphyrin dimers, respectively. Unlike all other ethene-bridged metalloporphyrin dimers reported earlier, in which 2e oxidation stabilizes only the trans form, such an oxidation of silver(II) porphyrin dimer stabilizes only the cis form because of the metallophilic interaction. Besides silver(II) ⋅⋅⋅ silver(II) interactions in cis silver(II) porphyrin dimer, stepwise oxidations also enabled us to achieve various hitherto-unknown silver(II) ⋅⋅⋅ silver(III) and silver(III) ⋅⋅⋅ silver(III) interactions, which thereby allow significant modulation of their structure and properties. The strength of Ag ⋅⋅⋅ Ag interaction follows the order Ag^II/Ag^II (d⁹/d⁹)<Ag^II/Ag^III (d⁹/d⁸)<Ag^III/Ag^III (d⁸/d⁸). Single-crystal XRD, X-ray photoelectron spectroscopy (XPS), ¹H NMR and EPR spectroscopy, and variable-temperature magnetic investigations revealed various oxidation states of silver and metallophilic interactions, which are also well supported by computational analysis.     

Control over the Self‐Assembly Modes of PtII Complexes by Alkyl Chain Variation: From Slipped to Parallel π‐Stacks

We report the self‐assembly of a new family of hydrophobic, bis(pyridyl) Pt^II complexes featuring an extended oligophenyleneethynylene‐derived π‐surface appended with six long (dodecyloxy ( 2 )) or short (methoxy ( 3 )) side groups. Complex 2 , containing dodecyloxy chains, forms fibrous assemblies with a slipped arrangement of the monomer units (d_Pt???Pt≈14 Å) in both nonpolar solvents and the solid state. Dispersion‐corrected PM6 calculations suggest that this organization is driven by cooperative π–π, C?H???Cl and π–Pt interactions, which is supported by EXAFS and 2D NMR spectroscopic analysis. In contrast, nearly parallel π‐stacks (d_Pt???Pt≈4.4 Å) stabilized by multiple π–π and C?H???Cl contacts are obtained in the crystalline state for 3 lacking long side chains, as shown by X‐ray analysis and PM6 calculations. Our results reveal not only the key role of alkyl chain length in controlling self‐assembly modes but also show the relevance of Pt‐bound chlorine ligands as new supramolecular synthons.     

Multi-Stimuli-Responsive Properties of Aggregation-Enhanced Emission-Active Unsymmetrical PtII Metallomesogens through Self-Assembly

Herein, we report a series of unsymmetrical bispyrazolate-type Pt^II compounds that exhibit mesomorphism at low temperatures and photophysical multi-stimuli-responsive properties. These Pt^II compounds show a great ability to be self-assembled by intermolecular Pt⋅⋅⋅Pt interactions in the solid state, so generating a columnar stacking of molecules that is responsible for the formation of the mesophases. By controlling the nature of the molecular assembly through external stimuli such as the temperature, the pressure, or the presence of vapours or solvents, it is possible to modulate the luminescence behaviour of these materials. The Pt^II monomers emit a greenish light, whereas aggregation of molecules produces a redshifted emission. These metallomesogens also show a high stability and successive grinding/fuming cycles can be performed without degradation of the sample. The application of these materials is very attractive as rewritable luminescent platforms, and their use is already demonstrated.     

Multinuclear PtII Complexes: Why Three is Better Than Two to Enhance Photophysical Properties

The self-assembly of platinum complexes is a well-documented process that leads to interesting changes of the photophysical and electrochemical behavior as well as to a change in reactivity of the complexes. However, it is still not clear how many metal units must interact in order to achieve the desired properties of a large assembly. This work aimed to clarify the role of the number of interacting Pt^II units leading to an enhancement of the spectroscopic properties and how to address inter- versus intramolecular processes. Therefore, a series of neutral multinuclear Pt^II complexes were synthesized and characterized, and their photophysical properties at different concentration were studied. Going from the monomer to dimers, the growth of a new emission band and the enhancement of the emission properties were observed. Upon increasing the platinum units up to three, the monomeric blue emission could not be detected anymore and a concentration independent bright-yellow/orange emission, due to the establishment of intramolecular metallophilic interactions, was observed.     

The Role of Substituent Effects in Tuning Metallophilic Interactions and Emission Energy of Bis‐4‐(2‐pyridyl)‐1,2,3‐triazolatoplatinum(II) Complexes

The photoluminescence spectra of a series of 5‐substituted pyridyl‐1,2,3‐triazolato Pt^II homoleptic complexes show weak emission tunability (ranging from λ=397–408 nm) in dilute (10^?6 M ) ethanolic solutions at the monomer level and strong tunability in concentrated solutions (10^?4 M ) and thin films (ranging from λ=487–625 nm) from dimeric excited states (excimers). The results of density functional calculations (PBE0) attribute this “turn‐on” sensitivity and intensity in the excimer to strong Pt–Pt metallophilic interactions and a change in the excited‐state character from singlet metal‐to‐ligand charge transfer (¹MLCT) to singlet metal‐metal‐to‐ligand charge transfer (¹MMLCT) emissions in agreement with lifetime measurements.     

Synergistic Effects of Metals in a Promising RuII−PtII Assembly for a Combined Anticancer Approach: Theoretical Exploration of the Photophysical Properties

Ru^II?Pt^II complexes are a class of bioactive molecules of interest as anticancer agents that combine a light‐absorbing chromophore with a cisplatin‐like unit. The results of a DFT and TDDFT investigation of a Ru^II complex and its conjugate with a cis‐PtCl₂ moiety reveal that a synergistic effect of the metals makes the assembly a promising multitarget anticancer drug. Inspection of type I and type II photoreactions and spin–orbit coupling computations reveals that the cis‐PtCl₂ moiety improves the photophysical properties of the Ru^II chromophore, ensuring efficient singlet oxygen generation and making the assembly suitable for photodynamic therapy. At the same time, the Ru^II chromophore promotes a new alternative activation mechanism of the Pt^II ligand via a triplet metal‐to‐ligand charge transfer (³M LCT) state, before reaching the biological target. The importance of the supramolecular architecture is accurately derived, opening interesting new perspectives on the use of bimetallic Ru^II?Pt^II assemblies in a combined anticancer approach.     

Hydrogen Bonding Directed Supramolecular Polymerisation of Oligo(Phenylene‐Ethynylene)s: Cooperative Mechanism,Core Symmetry Effect and Chiral Amplification

The design of supramolecular motifs with tuneable stability and adjustable supramolecular polymerisation mechanisms is of crucial importance to precisely control the properties of supramolecular assemblies. This report focuses on constructing π‐conjugated oligo(phenylene ethynylene) (OPE)‐based one‐dimensional helical supramolecular polymers that show a cooperative growth mechanism. Thus, a novel set of discotic molecules comprising a rigid OPE core, three amide groups, and peripheral solubilising wedge groups featuring C₃ and C₂ core symmetry was designed and synthesised. All of the discotic molecules are crystalline compounds and lack a columnar mesophase in the solid state. In dilute methylcyclohexane solution, one‐dimensional supramolecular polymers are formed stabilised by threefold intermolecular hydrogen bonding and π–π interactions, as evidenced by ¹H NMR measurements. Small‐angle X‐ray and light scattering measurements reveal significant size differences between the columnar aggregates of C₃‐ and C₂‐symmetrical discotics, that is, the core symmetry strongly influences the nature of the supramolecular polymerisation process. Temperature‐dependent CD measurements show a highly cooperative polymerisation process for the C₃‐symmetrical discotics. In contrast, the self‐assembly of C₂‐symmetrical discotics shows a smaller enthalpy release upon aggregation and decreased cooperativity. In all cases, the peripheral stereogenic centres induce a preferred handedness in the columnar helical aggregates. Moreover, one stereogenic centre suffices to fully bias the helicity in the C₂‐symmetrical discotics. Finally, chiral amplification studies with the C₃‐symmetrical discotics were performed by mixing chiral and achiral discotics (sergeants‐and‐soldiers experiment) and discotics of opposite chirality (majority‐rules experiment). The results demonstrate a very strong sergeants‐and‐soldiers effect and a rather weak majority‐rules effect.     

An Alkyne‐Appended,Click‐Ready PtII Complex with an Unusual Arrangement in the Solid State

To better understand the range of cellular interactions of Pt^II‐based chemotherapeutics, robust and efficient methods to track and analyze Pt targets are needed. A powerful approach is to functionalize Pt^II compounds with alkyne or azide moieties for post‐treatment conjugation through the azide–alkyne cycloaddition (click) reaction. Herein, we report an alkyne‐appended cis‐diamine Pt^II compound, cis‐[Pt(2‐(5‐hexynyl)amido‐1,3‐propanediamine)Cl₂] ( 1 ), the X‐ray crystal structure of which exhibits a combination of unusual radially distributed CH/π(CC) interactions, Pt Pt bonding, and NH:O/NH:Cl hydrogen bonds. In solution, 1 exhibits no Pt alkyne interactions and binds readily to DNA. Subsequent click reactivity with nonfluorescent dansyl azide results in a 70‐fold fluorescence increase. This result demonstrates the potential for this new class of alkyne‐modified Pt compound for the comprehensive detection and isolation of Pt‐bound biomolecules.     

Development of a Pre‐assembled Through‐Bond Energy Transfer (TBET) Fluorescent Probe for Ratiometric Sensing of Anticancer Platinum(ll) Complexes

Fluorescence microscopy has emerged as an attractive technique to probe the intracellular processing of Pt‐based anticancer compounds. Herein, we reported the first through‐bond energy transfer (TBET) fluorescent probe NPR1 designed for sensitive detection and quantitation of Pt^II complexes. The novel TBET probe was successfully applied for ratiometric fluorescence imaging of anticancer Pt^II complexes such as cisplatin and JM118 in cells. Capitalizing on the ability of the probe to discriminate between Pt^II complexes and their Pt^IV derivatives, the probe was further applied to study the activation of Pt^IV prodrug complexes that are known to release active Pt^II species after intracellular reduction.     

An Alkyne‐Appended,Click‐Ready PtII Complex with an Unusual Arrangement in the Solid State

To better understand the range of cellular interactions of Pt^II‐based chemotherapeutics, robust and efficient methods to track and analyze Pt targets are needed. A powerful approach is to functionalize Pt^II compounds with alkyne or azide moieties for post‐treatment conjugation through the azide–alkyne cycloaddition (click) reaction. Herein, we report an alkyne‐appended cis‐diamine Pt^II compound, cis‐[Pt(2‐(5‐hexynyl)amido‐1,3‐propanediamine)Cl₂] ( 1 ), the X‐ray crystal structure of which exhibits a combination of unusual radially distributed CH/π(C?C) interactions, Pt? Pt bonding, and NH:O/NH:Cl hydrogen bonds. In solution, 1 exhibits no Pt? alkyne interactions and binds readily to DNA. Subsequent click reactivity with nonfluorescent dansyl azide results in a 70‐fold fluorescence increase. This result demonstrates the potential for this new class of alkyne‐modified Pt compound for the comprehensive detection and isolation of Pt‐bound biomolecules.     

Flat vs. Folded Chelate Rings in cis‐PtIIa2 (a = NH3, a2 = en,a2 = 2, 2′‐bpy) Complexes of Twofold Substituted Diazine Ligands

Acid‐base and ligating properties of three bis(substituted)pyrazine (pz) and pyrimidine (pym) ligands (pyrazine‐2, 5‐dicarboxylic acid, 2, 5‐pzdcH2, 2, 3‐bis(pyridine‐2‐yl)pyrazine, 2, 3‐bppz, pyrimidine‐4, 6‐dicarboxylic acid, 4, 6‐pmdcH₂) toward cis‐Pt^IIa₂ (a = NH₃, a₂ = en, a₂ = 2, 2′‐bpy) have been studied. Combinations of pz‐N/pym‐N with donor atoms of the substituents lead to 5‐membered platinum chelates, but exclusive N, N‐coordination through the pyridyl substituents of 2, 3‐bppz can lead to a 7‐membered platinum chelate with a characteristic L‐shape of the resulting cation. It is observed for Pt^II(2, 2′‐bpy), yet not for Pt^II(en), and is a consequence of differences in sterical interactions between the 2, 3‐bppz ligand and the coligands of Pt^II.     

Supramolecular Polymerization of C3‐Symmetric Organogelators: Cooperativity,Solvent, and Gelation Relationship

A systematic study of the influence of solvent and the size of C₃‐symmetric discotics on their supramolecular polymerization mechanism is presented. The cooperativity of the self‐assembly of the reported compounds is directly related to their gelation ability. The two series of C₃‐symmetric discotics investigated herein are based on benzene‐1,3,5‐tricarboxamides (BTAs) and oligo(phenylene ethynylene)‐based tricarboxamides (OPE? TAs) that are peripherally decorated with achiral ( 1 a and 2 a ) or chiral N‐(2‐aminoethyl)‐3,4,5‐trialkoxybenzamide units ( 1 b and 2 b ). The supramolecular polymerization of compounds 1 a , b and 2 a , b has been exhaustively investigated in a number of solvents and by using various techniques: variable‐temperature circular dichroism (VT‐CD) spectroscopy, concentration‐dependent ¹H NMR spectroscopy, and isothermal titration calorimetry (ITC). The supramolecular polymerization mechanism of compounds 2 is highly cooperative in solvents such as methylcyclohexane and toluene and is isodesmic in CHCl₃. Unexpectedly, chiral compound 1 b is practically CD‐silent, in contrast with previously reported BTAs. ITC measurements in CHCl₃ demonstrated that the supramolecular polymerization of BTA 1 a is isodesmic. These results confirm the strong influence of the π‐surface of the central aromatic core of the studied discotic and the branched nature of the peripheral side chains on the supramolecular polymerization. The gelation ability of these organogelators is negated in CHCl₃, in which the supramolecular polymerization mechanism is isodesmic.     

A Multi‐action and Multi‐target RuII–PtIV Conjugate Combining Cancer‐Activated Chemotherapy and Photodynamic Therapy to Overcome Drug Resistant Cancers

Pt^II complexes are commonly used to treat cancer. To reduce their side effects and improve their pharmacological properties, Pt^IV complexes are being developed as prodrug candidates that are activated by reduction in cancer cells. Concomitantly, Ru^II polypyridine complexes have gained much attention as photosensitizers for use in photodynamic therapy due to their attractive characteristics. In this article, a novel Pt^IV–Ru^II conjugate, which combines cancer activated chemotherapy with PDT, is presented. Upon entering the cancer cell, the Pt^IV centre is reduced to Pt^II and the axial ligands including the Ru^II complex and phenylbutyrate are released. As each component has its individual targets, the conjugate exerts a multi‐target and multi‐action effect with (photo‐)cytotoxicity values upon irradiation up to 595 nm in the low nanomolar range in various (drug resistant) 2D monolayer cancer cells and 3D multicellular tumour spheroids.