Fluorinated (hetero)cyclic compounds have garnered attention over the years, offering key building blocks in medicinally relevant molecules. However, the synthesis of fluorinated tetrahydrofurans remains a synthetic challenge to reach. Herein, we developed an efficient and robust approach for the synthesis of cis-(ethoxycarbonyl)difluoromethylated tetrahydrofurans. Using the inexpensive Pd/C catalyst, the diastereoselective hydrogenation of functionalized CF2CO2Et-containing furans was achieved under mild reaction conditions. Access to unprecedented cis-fluorinated tetrahydrofurans with isolated yields of up to 74% and diastereomeric ratios up to 95:5 (12 examples) was reached. Pleasingly, under slightly modified reaction conditions, 5-arylated CF2CO2Et-containing furans were smoothly converted into the valuable α,α-difluoro-β-hydroxyesters (five examples, up to 66% yield). Overall, the protocol exhibited good functional-group tolerance and was easily scaled up. The synthetic utility of the CF2CO2Et moiety was further illustrated by its conversion into various other fluorinated groups.
Electrocatalytic nitrate (NO3 -) reduction offers a sustainable route for simultaneous NO3 - remediation and ammonia (NH3) production, yet its efficiency is limited by the competing hydrogen evolution reaction (HER) and the imbalance between NO3 - activation and hydrogen supply. Herein, Co-Cu bimetallic sulfide nanoflowers were synthesized via a one-step hydrothermal method and optimized for NO3 - to NH3 conversion. The Co0.9Cu0.1S nanoflowers, assembled from two-dimensional nanosheets, delivered 97.83% ± 1.71% nitrate conversion, nearly complete NH4 +-N selectivity, and a Faradaic efficiency of 98.52% ± 0.83% at -0.75 V vs. RHE. Systematic Co/Cu-ratio studies, electrochemical kinetics, Bode analysis, hydrogen adsorption/desorption behavior, and XPS results reveal that Cu promotes NO3 - activation and electronically modulates Co sites, while Co facilitates reactive hydrogen generation and utilization. This synergy enables on-demand hydrogen supply, directing hydrogen toward NO3 - hydrogenation rather than HER. pH-dependent tests further identify a neutral electrolyte as favorable for balancing proton supply and competitive HER.
The "soft" pyridine stabilized FLP tBu2In(py)CH2PtBu2 (1·py) was reacted with SO2, PhNCO, PhNSO, azobenzene, pyridazine, 1,2,4,5-tetrazine, tosylaziridine, and hydrazine, respectively. The reactivity can be roughly classified into three types of FLP activation. (a) Typical FLP-type reactivity is observed for the reaction with azobenzene and tosylaziridine, with the formation of 1,2-addition or ring-opening products, respectively. (b) "Soft" FLP-type reactivity occurs toward substrates containing multiple sites for FLP attack-in this case 1·py prefers coordination to the "softer" binding site, resulting in the formation of "soft" isomers of possible FLP adducts, as was demonstrated for PhNCO and PhNSO. (c) An unexpected reactivity results that can be described as a "masked" In/C-FLP; when 1·py was reacted with SO2, an insertion dimer formed, with the methylene bridge connected to the sulfur atom; the reaction of 1·py with hydrazine afforded a four-membered hydrazide heterocycle, under loss of the methylene bridge as MePtBu2, instead of the reaction with the PtBu2 fragment, pyridine, or excess hydrazine. The products were characterized by a variety of NMR spectroscopy methods supported by X-ray crystallography as well as quantum-chemical calculations for insights into the thermodynamics and selectivity of product formation.
Phenalenones (PNs), popular as antifungal, antimicrobial, and anticancer agents, are a fascinating class of naturally occurring photosensitizers. In spite of their importance, doping of the main core of PNs remains unexplored. Herein, we report a facile and green approach to prepare N-doped PNs or aza phenalenones (APNs) for the first time. We accomplished the goal by trapping unstable peri-naphthoisatogen, prepared using a modified aldrone condensation reaction. Different types of primary amines were used as nucleophile to synthesize seven APNs. Structures of the APNs were unambiguously characterized using NMR spectroscopy, mass spectrometry, and x-ray crystallography. Anticancer activities of the APNs were evaluated against oral cancer cells. Among them, the APN derivative of 3-aminopyridine demonstrated the most potent anticancer activity with high selectivity against oral cancer cells. We further investigated the mechanism underlying the anticancer activity of this lead compound.
The synthesis and characterization of organo-selenium compounds have attracted considerable interest for decades, driven by the search for efficient catalysts and bioinspired antioxidants; the investigation and exploitation of selenium─metal motifs in biological and medicinal chemistry represent a recent development and constitute the focus of this review. Selenoproteins are targets of metal ions like mercury and cadmium, whose toxicity is associated with the formation of stable selenium─metal bonds impairing protein function. On the other hand, selenium─metal bonding provides a strategy for tuning both chalcogen and metal reactivity, potentially enhancing the pharmacological performance of metallodrugs. Coordination to transition metals can modify redox potentials, bond polarization, and reactivity, thereby enabling multifunctional compounds combining metal-based pharmacophores with the redox activity of selenium. These systems may modulate reactive oxygen species, inhibit enzymes, and enhance selective cytotoxicity toward cancer cells. The formation of selenium─metal bonds in biological environment can also alter the function of metalloproteins, accounting for the toxicity of organoselenides. By combining experimental structural and reactivity properties with mechanistic insights from computational chemistry, we highlight the unifying concepts that govern selenium─metal bonding and to illustrate how these concepts can guide the rational design of new classes of selenium-based functional molecules.
The synthesis of bioactive molecules through one-pot multicomponent reactions under mild conditions is of significant interest for medicinal chemistry, though largely unexplored and challenging. Herein, we have reported a new Y(III)-based chemically stable framework, IITKGP-65, with abundant active catalytic sites, which exhibited excellent stability in open air, water, and even in acidic medium. The activated framework, IITKGP-65a, has been utilized as a Lewis acid-driven heterogeneous catalyst for the synthesis of bioactive chromeno[2,3-d]pyrimidin-8-amine derivatives. Notably, synthesis of these compounds has not yet been reported in the literature using any coordination polymer (CP) or metal-organic framework (MOF)-based catalyst. Interestingly, a good to excellent yield was achieved even with a low catalyst loading of our developed catalyst for a wide range of substrate scopes, along with excellent recyclability without any loss of structural integrity. Most importantly, to demonstrate practical applicability, we synthesized four chromeno[2,3-d]pyrimidin-8-amine derivatives exhibiting antibacterial activity using a green ethanol medium. The facile accessibility, robust structural framework, outstanding catalytic performance, and excellent recyclability collectively underscore the potential of the developed framework, IITKGP-65, as an efficient catalyst. Furthermore, these attributes extend its applicability to the environmentally friendly synthesis of complex bioactive molecules.
Monomeric, two-coordinate 13-electron PdI complexes are exceptionally rare due to their intrinsic instability and propensity for dimerization. In this study, we report that the bulky N-heterocyclic carbene (NHC) ligand DiMeIHeptCl (1,3-bis[2,6-bis(1-propylbutyl)phenyl]-4,5-dichloro-1,3-dihydro-2H-imidazol-2-ylidene) enables the generation and stabilization of a series of such species. Reduction of the dichloro PdII precursor affords PdCl(DiMeIHeptCl) (3), which serves as a platform for accessing Pd(OtBu)(DiMeIHeptCl) (4), Pd[N(SiMe3)2](DiMeIHeptCl) (5), and Pd(NH-2,4,6-tri-tertbutyl-C6H2)(DiMeIHeptCl) (6). These complexes adopt pseudolinear or bent geometries, as established by EPR spectroscopy, x-ray crystallography, and DFT calculations. Complexes 3 and 4 react with nucleophiles by an associative mechanism, which becomes impossible for sterically over-crowded 5. Kinetic and spectroscopic studies reveal divergent decay pathways, with 3 undergoing disproportionation and 4-6 decomposing via Pd─X bond homolysis to generate Pd0 species and transient organic radicals. Notably, these PdI complexes do not undergo oxidative addition with aryl halides, excluding PdI/III reactivity under these conditions. Electronic structure analysis shows the unpaired electron resides primarily on Pd and the X ligand, with minimal NHC involvement. These findings provide insight into low-coordinate PdI intermediates that may prove relevant to Pd(NHC) precatalyst activation.
Olympicene, or 6H-benzo[cd]pyrene, is a polycyclic aromatic hydrocarbon (PAH) with five fused six-membered rings arranged in a pattern reminiscent of the Olympic symbol. While functionalized olympicene-based materials have captivated attention for their unique graphene-fragment topology and aromaticity, their photoluminescent properties remain virtually unexplored. Here, we synthesize olympicene-core functionalized derivatives and report their "anomalous" photophysical properties. These olympicene derivatives display extensive vibronic structure and highly interacting electronic states. Such effects give rise to excited-state dynamics that are rare and unconventional in small PAH systems. Specifically, these olympicene derivatives exhibit dual fluorescence upon photoexcitation, accompanied by pronounced excitation-dependent emission behavior. Spectroscopic evidence demonstrates these behaviors arise from multiple singlet emissive states-an anti-Kasha locally excited (LE) state (Sn, n ≥ 2) and an intramolecular charge transfer (ICT) state. This work positions olympicene-functionalized derivatives as a new platform to study fundamental photophysics. Exploring these properties will lead to new and advanced optoelectronic applications.
Self-assembled macrocyclic dodecamers were found in the crystals of new pseudo-polymorphs of iso-tellurazole N-oxides. These structures are formed by molecules connected by NTe…O chalcogen bonds and are folded in a pattern that defines 89-153 Å3 cavities, which are large enough to host solvent molecules. These crystals only grow in the presence of molecular species that can act as guests alone (cyclohexane) or in combination with sodium cations (1,4-dioxane, tetrahydrofuran, and pyrazine). A solution rich in a sodium salt yielded a crystal featuring a cage-like aggregate of three tetramers bridged by sodium cations, suggesting a plausible route for the formation of the new macrocycles by reorganization of the chalcogen bonds.
This work reports the synthesis, characterization, and solution photophysical properties of para-trisubstituted triphenylamine (TPA) derivatives that preserve the threefold symmetry around the central nitrogen atom. By functionalizing the TPA core with three units of one of two representative boron-containing chromophores-BODIPY and subphthalocyanine (SubPc)-we directly compare how chromophore identity and molecular topology determine the optical response of the resulting star-shaped architectures. Whereas neither family exhibits significant solvatochromism in absorption, their fluorescence is strongly governed by both the solvent and the molecular architecture. The SubPc-based trimer undergoes efficient fluorescence quenching in all but the least polar solvent studied (Φ ≤ 2%, partially restored to 10% in methylcyclohexane), consistent with an effective intramolecular excited-state deactivation pathway. In contrast, the BODIPY-based trimer remains strongly quenched in polar media while developing a new red-shifted emission band (λem = 606 nm) with a markedly enhanced fluorescence quantum yield (Φ = 26%) in toluene. Comparison with the corresponding monomeric reference compounds demonstrates that these distinctive photophysical properties arise primarily from the threefold star-shaped architecture rather than from the intrinsic optical properties of the individual chromophores. These findings establish molecular topology as an effective design parameter for tuning excited-state dynamics in multichromophoric TPA-based systems.
Hydrogels have garnered significant interest as soft materials due to their flexibility, high water content, and biocompatibility. Alginate/polyacrylamide (Alg/PAAm) double-network (DN) hydrogels are particularly promising for wearable electronics, strain sensors, and soft electrolytes owing to their toughness and structural stability. However, the conventional soaking method for ion incorporation requires prolonged diffusion and often generates internal concentration gradients, leading to structural heterogeneity. This study introduces a one-pot strategy that incorporates NaCl directly into the precursor solution, enabling simultaneous gelation and ion integration. Elemental analyses indicate a more spatially consistent Na and Cl distribution across the examined surface regions of the one-pot hydrogel compared with the soaking-derived hydrogel. Furthermore, NaCl incorporation influences network formation primarily by modifying the ionic environment and hydration state rather than by creating new covalent bonds. The resulting hydrogels exhibit a composition-dependent trade-off between mechanical reinforcement and ionic transport. NaCl concentrations of 1.5-2.0 wt% provide a favorable balance among stiffness, strength, and deformability, whereas ionic conductivity reaches its maximum at 12.5 wt%. These findings indicate that no single NaCl concentration is optimal for all performance requirements and that the salt content should instead be tailored to the intended application.
Modification of boranils with dual state emissions in solution and solid states have been targeted by introducing free amine functional group at the terminal position. Herein, we designed and synthesized four new primary amine-substituted benzothiazole-based boranils from substituted salicylaldehyde. Their photophysical properties were investigated through steady-state absorption and emission measurements in both solution- and solid-states. X-ray structure analysis of the boranils revealed that the benzothiazole rings bearing the amine functional group are highly twisted, thereby avoiding the detrimental exciton interaction between the dimers and enabling emission in the solid state. In the solution-state, the naphthalene and methoxy substituted boranils exhibited significant intramolecular charge transfer and a large Stokes shift of > 150 nm. Julolidine or diethylamine substituted boranils exhibited reversible acid-base responsiveness via fluorescence ON-OFF properties. On the other hand, protonation and deprotonation of naphthalene and methoxy substituted boranils showed reversible blue and red shift emission. Computational studies revealed that the photo-induced electron transfer (PET) and photo-induced charge transfer (PICT) process were responsible for fluorescence enhancement and wavelength shift upon trifluoroacetic acid (TFA) treatment. Based on the solvent dependent wide emissive range, methoxy substituted boranil was further utilized for the generation of white light emission with anthracene as an ancillary component.
The final step in revealing the porosity of most metal-organic frameworks (MOFs), the ultimate step of the activation process, involves removal of solvent from the pores. This is commonly accomplished with the application of vacuum and heat; whereas some MOFs are readily activated under mild conditions, others must be heated to the point where decomposition can compete with activation. This latter class includes MOFs where the coordination of the metals to solvent must be disrupted for full activation. Here, the details of the solvent removal process are elucidated for two isostructural MOFs comprising divalent metals linked with 2,5-dioxidoterephthalate: Mg-MOF-74 and Zn-MOF-74. Using computational and spectroscopic data, structural and electronic changes undergone by the MOF are elucidated, providing insight into discrete intermediate states during the solvent removal process. Additionally, powder x-ray diffraction is analyzed to reveal features that are indicative of successful activation. These results provide a basis to design more efficient and effective MOF activation procedures.
The synthesis and characterization of a new family of N-boron-functionalized anionic NHCs (NBA-NHCs), IiPrB(CN)3 - (5), IiPr(C2F5)BF2 - (6), IMesB(CN)3 - (7), and IMes(C2F5)BF2 - (8), accessible on gram-scale from air- and moisture-stable precursors, is reported. Multinuclear NMR, IR spectroscopy, and single-crystal X-ray diffraction confirm highly electron-rich carbenic carbon centers and strengthened B-N interactions in these molecules. Selenium adducts 9-12 of these NBA-NHCs indicate an enhanced π-acceptor character relative to neutral NHCs, while Tolman electronic parameters of nickel tricarbonyl complexes [(NBA-NHC)Ni(CO)3]-K+ 13-16 demonstrate their strong donor ability, similar to dianionic carbenes. Steric maps and buried volume (%Vbur) analyses of linear gold(I) complexes [(NBA-NHC)Au(PPh3)] 17-20 reveal tunable steric profiles, ranging from anisotropic to strongly shielding environments by varying the N-substituents. These results establish NBA-NHCs as a modular ligand platform enabling control of electronic properties and steric demand at the metal center for future applications in coordination chemistry and catalysis.
ABSTRACT The difructose dianhydride I synthase/hydrolase catalyzes the reversible transformation of inulobiose into difructose dianhydride I, a component of caramel. The proposed reaction mechanism of such a transformation consists of a glycosylation step followed by a cyclization to yield the dianhydride from the disaccharide. Here, we make use of extensive hybrid QM/MM metadynamics studies to shed light on the molecular basis of it. Our simulations show that the global reaction for the transformation of inulobiose by is slightly exergonic in good agreement with the experimental data. Furthermore, we observe that the glycosylation step is the rate‐limiting step. Interestingly, our work shows that the –1 sugar of inulobiose changes from an initial E conformation into a E puckering via the conformational pathway E E / T E E . Our calculations highlight that in the cyclization step, the three residues E85, K147, and N226 are essential for the rotation of the +1 sugar in the substrate to facilitate the intramolecular attack of oxygen O1' to the anomeric carbon. Prompted by these results, we expressed and assayed the N226A variant. Enzyme activity data confirm an important role for N226 during the cyclization step but show that it is dispensable for the hydrolysis step.
Prostate cancer (PCa) remains a significant clinical challenge, particularly in localized therapy, where unmet medical needs persist for effective and targeted treatments. This study introduces an innovative solution by developing the first responsive spermine (Spm) hydrogel with an autonomous sensing function, designed to advance local therapy for PCa. Our hydrogel effectively loads Spm and releases Spm in the acidic tumor microenvironment (TME), providing a responsive therapeutic platform. Incorporating the di-lysine-7-nitrobenzofurazan (NBD-KK) dye, which is initially quenched by aggregate formation within the hydrogel, the release of Spm can be monitored in real time. With its autonomous sensing capability within the tumor, re-administration of the hydrogel can be determined based on real-time monitoring of Spm release. Notably, in vivo results indicate a safe and effective dosage of 0.53 mg of Spm in the hydrogel for prostate tumor inhibition. This novel approach holds promise for enhancing local therapy in PCa and improving the quality of life for patients.
Persilylated and related silyl anions have emerged as powerful reagents for the construction of metal-silyl complexes across a wide range of elements. Owing to their strong σ-donating ability and extreme steric bulk, these ligands stabilize highly reactive, low-coordinate metal centers and enable access to unusual bonding motifs and electronic structures. This review summarizes advances in the synthesis, structure, bonding, and reactivity of group 3-10 metal-silyl complexes prepared using persilylated and related silyl anions. Synthetic strategies, particularly salt metathesis with metal halide precursors and related methodologies, are highlighted as versatile routes to both early and late transition metal systems. Recent developments in multidentate and chelating oligosilyl ligands are also emphasized for their role in controlling coordination environments and enabling unique geometries. The reactivity of these complexes, including insertion reactions, σ-bond metathesis, and small-molecule activation, is discussed alongside their catalytic applications in polymerization, hydrosilylation, and hydrogenation. Overall, persilylated silyl ligands provide a versatile platform for advancing organometallic chemistry and catalytic science.
Polyacrylamide (PAM) hydrogels are attractive soft materials owing to their high-water content and tunable network structure. However, their limited strength and toughness restrict practical use. Here, prevulcanized natural rubber (NR) latex was incorporated into an acrylamide precursor before polymerization to prepare NR latex-reinforced PAM (PAM@NR) hydrogels. The PAM matrix served as a continuous hydrophilic network, while NR latex particles served as flexible biobased dispersed domains. NR incorporation produced a denser freeze-dried surface morphology with NR-rich domains and increased the storage and loss moduli, indicating enhanced network stiffness and a stronger dissipative response. At a PAM-to-dry-NR mass ratio of 5:5 (PAM@NR-5:5), the hydrogel achieved a tensile strength of 255.0 kPa, elongation at break of 401%, and toughness of 809.1 kJ m- 3, representing increases of 278.3%, 165.6%, and 1207.1% compared with PAM, respectively. NR incorporation also suppressed swelling and slowed water loss under ambient conditions. These results suggest that prevulcanized NR latex can serve as a biobased reinforcing phase to improve the mechanical performance of PAM hydrogels.
Platinum(II)-based chemotherapeutics remain a cornerstone in solid tumor oncology but are severely constrained by systemic toxicities and drug resistance. Platinum(IV) (Pt(IV)) prodrugs have emerged as a powerful platform to circumvent these limitations, capitalizing on their kinetic inertness during systemic circulation and selective activation within reductive microenvironments to release cytotoxic Pt(II) species and bioactive axial ligands. However, traditional endogenously activated Pt(IV) complexes frequently suffer from premature reduction, leading to off-target toxicity in healthy tissues. To address these bottlenecks, the deployment of energy stimuli, including visible/near-infrared light, ultrasound, and ionizing radiation (x-rays/radionuclides), has enabled an emerging strategy toward the spatiotemporally controlled activation of Pt(IV) prodrugs for precision chemotherapy. This review comprehensively encapsulates recent breakthroughs in energy-triggered small-molecule Pt(IV) prodrugs. We categorize and analyze these systems into photoactivatable, tumor-targeting, organelle-specific, ultrasound-responsive, and radiochemically activatable designs. Within each section, the underlying chemical design principles, responsive activation mechanisms, and in vitro/in vivo therapeutic efficacies are elucidated. Finally, we address current clinical translation barriers, including dark stability, hypoxic resistance, and dosimetry inconsistencies, offering a rational roadmap for the development of next-generation, clinically translatable, smart platinum therapeutics.
Heterogenized molecular catalysts commonly rely on covalent grafting to solid supports. Cleavage of these linkages under catalytic conditions, however, can compromise structural definition and control at the interface. Here, we introduce a ligand-encoded anchoring strategy in which a platinum(II) bis(NHC) complex is immobilized on mesoporous silica (SBA-15) exclusively through directional, non-covalent F-Si interactions. The molecular pre-catalyst trans-[Pt(LF)2Cl2] was structurally characterized by single-crystal X-ray diffraction and multinuclear solution-state NMR spectroscopy. Advanced solid-state MAS NMR experiments, including 19F{29Si} REDOR, combined with molecular dynamics simulations, establish well-defined F-Si contacts with internuclear distances on the Å-scale and reveal the organization of the pre-catalyst at the silica interface. A model hydrosilylation reaction demonstrates catalytic activity and retention of the molecular species on the support during turnover. This work establishes non-covalent interface engineering as a viable strategy for structurally defined heterogenized catalysis.
