Pyridyl Groups Research Articles

Azopyridine Aqueous Electrochemistry Enables Superior Organic AZIBs.

Azo compounds (AZO), such as azobenzene, are classic organic electrode materials featuring a redox potential close to Zn/Zn2+. Recent studies show that azobenzene could work as a cathode in aqueous zinc-ion batteries (AZIBs), providing a voltage output of around 0.7 V. However, the energy storage mechanism of AZO cathodes in AZIBs remains unclear, and their practical usage in AZIBs is hindered by the low voltage. In this study, azopyridine isomers, the hydrophilic analogues of azobenzene, were adopted as cathodes for AZIBs, and the energy storage mechanism was unveiled through aqueous electrochemical studies. Through in situ electrochemical characterizations and theoretical computations, we reveal that both the electron-withdrawing effect of the pyridyl group and the H+-involved -N = N-/-NH-NH- redox reaction uplift the redox potential of the azopyridine cathodes. These findings led to the first AZO-based AZIB, providing a voltage output of 1.4 V. The proposed air-stable AZIBs deliver a high energy/power density and a capacity of around 200 mAh g-1. This work discovers different azopyridine electrochemistry in aqueous and organic electrolytes and enabling AZIBs to outperform its competitors from the AZO family.

Tailoring Electrocatalytic Hydrogen Evolution Activity in Topological Triangular Metal–Organic Frameworks

AbstractMetal–organic frameworks (MOFs) have attracted considerable attention in catalysis due to their exceptional structural and chemical tunability. However, high electrical conductivity is rare in MOFs, hindering their practical applications toward catalytic reactions. Recently, 2D topological MOFs stand out for the unique topologically nontrivial electronic structures. Particularly, their high electrical conductivity and chemical tunability make them promising candidates as high‐performance catalysts. In this study, theoretical investigations are conducted into the intrinsic electronic properties and chemical activity of a 2D topological Cu‐1,3,5‐tris(pyridyl)benzene (Cu‐TPyB) framework. It is found that the coordination environment of Cu with pyridyl groups plays a crucial role in modulating the electron density around the Fermi level, thereby enhancing the catalytic activity of Cu‐TPyB toward electrochemical hydrogen evolution reaction (HER). Furthermore, substituting the single embedded Cu atom with Cu3 and Cu4Bi3 clusters further increases the electron density around the Fermi level. Specifically, the Cu4Bi3‐TPyB framework exhibits superior HER activity, which is attributed to its high electron density contributed by the p orbitals of Bi and the d orbitals of Cu. This work introduces a novel approach for optimizing the catalytic activity of 2D MOFs and developing high‐performance catalysts.

Mechanochromic and Solvent-Induced Luminescence of a Supramolecular Pt(II)-Bipyridine Complex with Di(4-pyridylmethyl)aminedithiocarbamate.

[Pt(bpy)(DPMACS2)]2Cl2•3H2O (1•3H2O) (bpy = 2,2'-bipyridine, DPMACS2 = di(4-pyridylmethyl)aminedithiocarbamate) was synthesized and characterized by X-ray diffraction studies, and its crystal structure displayed intermolecular Pt(II)···Pt(II) contacts of 3.471 and 5.065 Å. Upon excitation, 1•3H2O showed broad luminescence at 538 nm, which was red-shifted and enhanced to 560 nm while cooling to 77 K. To this end, the B3LYP/LanL2DZ calculation results were performed to clearly explain their excited-state origin. Moreover, complex 1•3H2O displayed a dramatic mechanochromic shift from 538 to 608 nm while grinding, and the above red-shift was also observed while exposed to air within 1 day, suggestive of the simultaneous mechanochromic and solvent-induced luminescence. It is noted that the luminescence almost reverted to the original luminescence at 535-542 nm upon immersion in various solvents for the ground samples of complex 1•3H2O. In addition, the luminescence for the acetone-immersed ground samples returned to 608 nm in 1 min. The possible interactions between halogenated solvents and the free pyridyl groups in DPMACS2, which were not expected for acetone, have been proposed to be responsible for such a dramatic difference in this study.

Electrochemical α‐Functionalization of N‐Aryl‐Activated Tertiary Amines

AbstractNumerous appropriately substituted pyridyl or phenyl groups serve as a particularly advantageous activation motif for the electrochemical oxidation of amines. Such groups enable a general, mild method for the electrochemical α‐functionalization of tertiary amines across numerous activating groups and amine scaffolds. Notably, the method accommodates an unprecedented range of nucleophile classes, allowing for the introduction of diverse functional groups to the readily prepared amine substrates. The utility of this method is then demonstrated through applications to unsymmetrical bisfunctionalization, site‐selective functionalization of N‐pyridyl amines vs. other activated amines, a formal synthesis of ivosidenib and the diversification of FDA‐approved drugs or natural product substrates.

Nucleosides as Organizing Architectural Moieties

Chemistry “beyond the molecule” is epitomized in nature by a plethora of relatively weak noncovalent interactions. The three-dimensional structures of most biopolymers are controlled with noncovalent interactions, either between different parts of the same strand (as in protein α-helices) or between two separate strands (as in the DNA duplex and protein β-sheet). While nature has refined the construction of biopolymers, our mastery of the subtle noncovalent interactions as synthetic tools is in an early stage of development. Only in the past two decades people begun to develop ways of mimicking the natural light-harvesting complexes by noncovalent assembly of porphyrin units aiming to obtain favored spacing and orientation between the chromophores. The construction of multi-chromophoric assemblies has led to resurgence of interest in coordination chemistry due to formation of ordered arrays directed through molecular recognition events. As a module in the construction of supramolecular assemblies, porphyrins and metallo-porphyrins can be exploited in two different ways: porphyrins can behave as donor building blocks insofar as they comprise meso-substituents, such as pyridyl groups, which can act as ligands that can suitably coordinate to metal cations, while metalloporphyrins can act as acceptor building blocks as soon as the metal atom inside the porphyrin core has at least one axial site available for coordination. For the last years, we have focussed on cofacial bis-porphyrin tweezers for host/guest interactions and investigated the possibilty to obtain self-coordinated molecular systems with predictable spectral and redox characteristics. We report here the synthesis of a di-nucleotide bearing pendant porphyrins dedicated to adopt a pre-organized coformation with face-to-face porphyrins, and capable to self-organize in a stable sandwich type complexe with bidentate base such as DABCO.1 Using a similar strategy as the one used in antisense research, an artificial nucleotidic backbone was built from modified deoxy-uridine units linked with a more rigid linker than the phosphodiester moieties found in natural oligonucleotides. Antisense research uses modified oligonucleotides, less flexible than natural strands, to pre-organize the system toward the obtaining of stable double helices between synthesized and natural oligonucleotides. A modified oligonucleotidic backbone was here used to target a parallel conformation of the porphyrins appended to each deoxy-uridine moiety. To provide a rigid environment for the porphyrins, the uridine units were coupled in 3’-5’ stepwise fashion using ether-ester type of spacer of suitable length, and porphyrins were anchored to the uridine by means of robust carbon-carbon bonds.Earlier studies demonstrated that a peptidic linker doesn’t provide sufficient pre-organization to enhance significantly the association constant with bidentate bases such as DABCO on the contrary of some flexible linkers such as uridine or 2’-deoxyuridine. We document herein that the gain in stability for the formation of sandwich type host-guest complex with DABCO can be even greater when a dinucleotide linker is used. Such pre-organization increases the association constants by one to two orders of magnitude when compared to the association constants of the same bidentate ligands with a reference Zn(II) porphyrin. Comparison of these results with those obtained for rigid tweezers shows a better efficiency of the flexible nucleosidic dimers.We thus document the fact that the choice of rigid spacers is not the only way to pre-organize bis-porphyrins, and that some well-chosen nucleosidic linkers offer an interesting option for the synthesis of such devices. Furthermore, the chirality and enantio-purity of the nucleosidic linkers paves the way toward the selective complexation of enantio-pure bidentate guests and the resolution of racemates. Acknowledgements This work was supported by the CNRS and the French Ministry of Research. References Solladié, R. Rein, S. Bouatra, S. Merkas, C. Sooambar, I. Piantanida, M. Žinić, J. Porphyrins Phthalocyanines 2020, 24, 636-645.

A Reduced-Symmetry Pd2L4 Cage from a Heterotopic Dipyridyl Ligand.

Two dipyridyl ligands, L3,3 and L3,4, have been used in combination with palladium(II) in the construction of metallosupramolecular species that show anion-dependent behavior in solution. A rare example of a low-symmetry (C2h) lantern-type cage is formed in one instance, [Pd2(L3,3)4]4+, while the isomeric ligand yields a larger double-walled square complex, [Pd4(L3,4)8]8+. [Pd2(L3,3)4](NO3)4 was isolated in crystalline form revealing two anions within the interior of the C2h-symmetry cage. The cage itself is held together by hydrogen bonding between "head-to-tail" pairs of ligands that reinforces the symmetry generated by the ditopic ligands. In solution, the cage with NO3- has sharp 1H nuclear magnetic resonance (NMR) signals at room temperature, while the BF4- analogue has broad signals that sharpen at higher temperatures or upon addition of (Bu4N)(NO3), highlighting the importance of the anion in templating or otherwise influencing self-assembly in solution. Altering the substitution position of one of the pyridyl rings yields a more "open" complex, with [Pd4(L3,4)8](NO3)8 being isolated as a crystalline solid. The double-walled square complex has a greater Pd···Pd separation due to the increased angle that the pyridyl groups subtend at the core of the ligand. NMR spectroscopy and mass spectrometry studies suggest a single species in the presence of nitrate but multiple species with tetrafluoroborate.

Platinum complexes with pyridyl derivatives of 1,2,4-triazole

The chemistry of platinum(II) and platinum(IV) with the ligands 3,4,5-tris(2-pyridyl)-4-H-1,2,4-triazole, L1, and 3,5-di(2-pyridyl)-4-(4-pyridyl)-4-H-1,2,4-triazole, L2, is described. The ligand L1 forms platinum(II) complexes [PtXY(κ2-N,N’-L1)] (X,Y = Cl,Cl; Cl,Me; Me,Me) by chelation while ligand L2 forms either analogous chelate complexes [PtXY(κ2-N,N’-L2)] (X,Y = Cl,Me; Me,Me) or acts as a monodentate ligand in forming trans-[PtCl2(SMe2)(κ1-N-L2)], in which only the 4-pyridyl group is coordinated. The electron-rich dimethylplatinum(II) complexes undergo oxidative addition reactions with methyl iodide to give [PtIMe3(κ2-N,N’-L1)], or with dichloromethane to give [PtClMe2(CH2Cl)(κ2-N,N’-L1)] or [PtClMe2(CH2Cl)(κ2-N,N’-L2)], each of which is formed as a mixture of three isomers. Structure determinations of several of these complexes are reported.

Sulfone Electrophiles in Cross-Electrophile Coupling: Nickel-Catalyzed Difluoromethylation of Aryl Bromides.

Fluoroalkyl fragments have played a critical role in the design of pharmaceutical and agrochemical molecules in recent years due to the enhanced biological properties of fluorinated molecules compared to their non-fluorinated analogues. Despite the potential advantages conferred by incorporating a difluoromethyl group in organic compounds, industrial adoption of difluoromethylation methods lags behind fluorination and trifluoromethylation. This is due in part to challenges in applying common difluoromethyl sources towards industrial applications. We report here the nickel-catalyzed cross-electrophile coupling of (hetero)aryl bromides with difluoromethyl 2-pyridyl sulfone, a sustainably sourced, crystalline difluoromethylation reagent. The scope of this reaction is demonstrated with 24 examples (67 ± 16% average yield) including a diverse array of heteroaryl bromides and precursors to difluoromethyl-containing preclinical pharmaceuticals. This reaction can be applied to small-scale parallel synthesis and benchtop scale-up under mild conditions. As sulfone reagents are uncommon electrophiles in cross-electrophile coupling, the mechanism of this process was investigated. Studies confirmed the formation of •CF2H instead of difluorocarbene. A series of modified difluoromethyl sulfones revealed that sulfone reactivity does not correlate exclusively with reduction potential and that coordination of cations or nickel to the pyridyl group is essential to reactivity, setting out parameters for matching the reactivity of sulfones in cross-electrophile coupling.

Using cocrystals as a tool to study non-crystallizing molecules: crystal structure, Hirshfeld surface analysis and computational study of the 1:1 cocrystal of (E)-N-(3,4-difluorophenyl)-1-(pyridin-4-yl)methanimine and acetic acid.

Using a 1:1 cocrystal of (E)-N-(3,4-difluorophenyl)-1-(pyridin-4-yl)methanimine with acetic acid, C12H8F2N2·C2H4O2, we investigate the influence of F atoms introduced to the aromatic ring on promoting π-π interactions. The cocrystal crystallizes in the triclinic space group P1. Through crystallographic analysis and computational studies, we reveal the molecular arrangement within this cocrystal, demonstrating the presence of hydrogen bonding between the acetic acid molecule and the pyridyl group, along with π-π interactions between the aromatic rings. Our findings highlight the importance of F atoms in promoting π-π interactions without necessitating full halogenation of the aromatic ring.

Low-lying LUMO Boosts Conductance in Antiaromatic Dibenzopentalene Versus Aromatic Analogues.

Antiaromaticity is a fundamental concept in chemistry, but the study of molecular wires incorporating antiaromatic units is limited. Despite initial predictions, very few studies show that antiaromaticity has a beneficial effect on electron transport. Dibenzo[a,e]pentalene (DBP) is a stable structure that displays appreciable antiaromaticity within the five-membered rings of the pentalene core. We have investigated derivatives of DBP furnished with pyridyl (Py) and F4-pyridyl (PyF4) anchor groups, and compared the conductance with purely aromatic phenyl and anthracene analogues. We find that the low-bias conductance of DBP-Py is approximately 60 % larger than that of the anthracene analogue Anth-Py and 250 % larger compared to the phenyl derivative Ph-Py. This is due to a better alignment of the LUMO with the gold Fermi level, which we confirm by conductance-voltage spectroscopy where the conductance of DBP-Py shows the greatest voltage-dependence. The F4-pyridyl compounds, which have lower LUMO energies compared to the pyridyl analogues, did not, however, form detectable molecular junctions. The strongly electron-withdrawing fluorine atoms reduce the donor capability of the nitrogen lone-pair to the point where stable N-Au bonds no longer form.

Syntheses of ruthenium complexes bearing unsymmetric tridentate Ethyl(2-pyridylmethyl)aminoacetate

Unsymmetric ethyl(2-pyridylmethyl)aminoacetate (epmaa-) is consisted by the central ethylamine connected with pyridyl and carboxy groups by methylene arms and coordinates to a metal center as a tridentate ligand. An aquadichlorido complex of ruthenium(III) bearing epmaa-, fac-[RuCl2(OH2)(epmaa)] ([1]), has been synthesized using the Ru-blue solution of RuCl3·nH2O in EtOH-H2O, and is a useful starting material for syntheses of ruthenium complexes. Four fac-[RuCl2(X)(epmaa)]m-type complexes (X = Cl; m = -1, CH3CN, dmso and NO; m = 0) were synthesized from [1] with simple manners under ambient conditions. Herein structures and properties of these complexes are discussed.

Discovery and Anticancer Screening of Novel Oxindole-Based Derivative Bearing Pyridyl Group as Potent and Selective Dual FLT3/CDK2 Kinase Inhibitor.

Protein kinases regulate cellular activities and make up over 60% of oncoproteins and proto-oncoproteins. Among these kinases, FLT3 is a member of class III receptor tyrosine kinase family which is abundantly expressed in individuals with acute leukemia. Our previous oxindole-based hit has a particular affinity toward FLT3 (IC50 = 2.49 μM) and has demonstrated selectivity towards FLT3 ITD-mutated MV4-11 AML cells, with an IC50 of 4.3 μM. By utilizing the scaffold of the previous hit, sixteen new compounds were synthesized and screened against NCI-60 human cancer cell lines. This leads to the discovery of a potent antiproliferative compound, namely 5l, with an average GI50 value against leukemia and colon cancer subpanels equalling 3.39 and 5.97 µM, respectively. Screening against a specific set of 10 kinases that are associated with carcinogenesis indicates that compound 5l has a potent FLT3 inhibition (IC50 = 36.21 ± 1.07 nM). Remarkably, compound 5l was three times more effective as a CDK2 inhibitor (IC50 = 8.17 ± 0.32 nM) compared to sunitinib (IC50 = 27.90 ± 1.80 nM). Compound 5l was further analyzed by means of docking and molecular dynamics simulation for CDK2 and FLT3 active sites which provided a rational for the observed strong inhibition of kinases. These results suggest a novel structural scaffold candidate that simultaneously inhibits CDK2 and FLT3 and gives encouragement for further development as a potential therapeutic for leukemia and colon cancer.

Tridentate Lewis Acids Based on Tribenzotriquinacene Chalices.

Chalice-shaped tridentate poly-Lewis acids (PLA) based on the tribenzotriquinacene (TBTQ) scaffold have been synthesised. Stannylation of the alkyne units, attached via phenyl-spacers to the benzhydrylic positions to the TBTQ scaffold, with Me2NSnMe3 afforded the trimethyltin substituted TBTQ derivative. Replacement of these tin functions with other elements resulted in rigid boron- and aluminium-functionalised PLAs. More flexible PLAs were obtained by hydrometallation reactions of the terminal alkyne groups of 4b,8b,12b-tris((ethynyl)phenyl)tribenzotriquinacene. The resulting poly-Lewis acids were tested for their acceptor abilities in host-guest experiments with suitable bases. Preliminary tests with pyridine led to the synthesis of a large tridentate base with three pyridyl groups attached to a TBTQ backbone. Complexation of this Lewis base with the PLAs resulted in the formation of aggregates, which were studied in solution in more detail by 1H DOSY NMR experiments regarding their size. Further experiments were performed with the tridentate bases 1,4,7-trimethyl-1,4,7-triazacyclononane and tris((dimethylphosphino)methyl)phenylsilane.

Replacement of sulfonamide by sulfoximine within a helicase-primase inhibitor with restricted flexibility

Helicase-primase is an interesting target for the therapy of herpes simplex virus (HSV) infections. Since amenamevir is already approved for varicella-zoster virus (VZV) and HSV in Japan and pritelivir has received breakthrough therapy status for the treatment of acyclovir-resistant HSV infections in immunocompromised patients, the target has sparked interest in me-too approaches. Here, we describe the attempt to improve nervous tissue penetration in Phaeno Therapeutics drug candidate HN0037 to target the latent reservoir of HSV by installing less polar moieties, mainly a difluorophenyl instead of a pyridyl group, and replacing the primary sulfonamide with a methyl sulfoximine moiety. However, all obtained stereoisomers exhibited a weaker inhibitory activity on HSV-1 and HSV-2.

Coordination Self-Assembled AuTPyP-Cu Metal-Organic Framework Nanosheets with pH/Ultrasound Dual-Responsiveness for Synergistically Triggering Cuproptosis-Augmented Chemotherapy.

Reactive oxygen species (ROS) mediated tumor cell death is a powerful anticancer strategy. Cuproptosis is a copper-dependent and ROS-mediated prospective tumor therapy strategy. However, the complex tumor microenvironment (TME), low tumor specificity, poor therapy efficiency, and lack of imaging capability impair the therapy output of current cuproptosis drugs. Herein, we designed a dual-responsive two-dimensional metal-organic framework (2D MOF) nanotheranostic via a coordination self-assembly strategy using Au(III) tetra-(4-pyridyl) porphine (AuTPyP) as the ligand and copper ions (Cu2+) as nodes. The dual-stimulus combined with the protonation of the pyridyl group in AuTPyP and deep-penetration ultrasound (US) together triggered the controlled release in an acidic TME. The ultrathin structure (3.0 nm) of nanotheranostics promoted the release process. The released Cu2+ was reduced to Cu+ by depleting the overexpressed glutathione (GSH) in the tumor, which not only activated the Ferredoxin 1 (FDX1)-mediated cuproptosis but also catalyzed the overexpressed hydrogen peroxide (H2O2) in the tumor into reactive oxygen species via Fenton-like reaction. Simultaneously, the released AuTPyP could specifically bind with thioredoxin reductase and activate the redox imbalance of tumor cells. These together selectively induced significant mitochondrial vacuoles and prominent tumor cell death but did not damage the normal cells. The fluorescence and magnetic resonance imaging (MRI) results verified this nanotheranostic could target the HeLa tumor to greatly promote the self-enhanced effect of chemotherapy/cuproptosis and tumor inhibition efficiency. The work helped to elucidate the controlled assembly of multiresponsive nanotheranostics and the high-specificity ROS regulation for application in anticancer therapy.

A Multivariate 2D Metal-Organic Framework with Open Metal Sites for Catalytic CO2 Cycloaddition and Cyanosilylation Reactions.

This work reports the synthesis of a dual functional 2D framework, {[Zn2(4-tpom)2(oxdz)2]·4H2O}n (1), at room temperature, where a bent dicarboxylate, oxdz2- (4,4'-(1,3,4-oxadiazole-2,5-diyl)dibenzoate), and a neutral flexible N-donor linker, 4-tpom (tetrakis(4-pyridyloxymethylene)methane), are utilized. Its single-crystal X-ray analysis indicated a 2-fold interpenetrated 2D framework having tetracoordinated Zn(II) centers and dangling pyridyl groups. Its further characterization was carried out with elemental microanalysis, FTIR spectroscopy, TG analysis, and powder X-ray diffraction. The tetracoordinated Zn(II) centers as active Lewis acidic sites and the N atoms of 4-tpom as Lewis basic sites in 1 are explored for its functioning as a heterogeneous catalyst in two important reactions, (i) cycloaddition of CO2 with various epoxides and (ii) cyanosilylation reaction under solvent-free conditions. We could successfully show the cycloaddition of styrene oxide with CO2 (99% conversion) under balloon pressure with low catalyst (0.2-0.3 mol %) and cocatalyst (0.5-0.75 mol %) loadings, which is otherwise difficult to achieve. It was observed that all the substrates (aromatic and aliphatic), irrespective of their sizes, showed conversion percentage >99%. In the cyanosilylation reaction, a conversion of 96% was obtained with 1.5 mol % of 1 at room temperature for 12 h. This framework emerged as an excellent recyclable catalyst for both the reactions.

Pd(II)‐Catalyzed [3+2] Annulation of N‐Aryl‐2‐aminopyridines and Alkynes toward N‐(2‐Pyridyl)indoles

AbstractA Pd‐catalyzed formal [3+2] oxidative annulation of N‐aryl‐2‐aminopyridines and alkynes through pyridyl group directed C−H activation has been developed. This methodology provides a mild and atom‐economic approach for the efficient synthesis of highly substituted indoles in moderate to good yields, which features with mild reaction conditions, good functional group compatibility, operational simplicity and easy scale‐up.

Fractionation of flavonols and anthocyanins in winemaking residues using molecularly imprinted cellulose‐synthetic hybrid particles with pyridyl active surface

AbstractHybrid cellulose‐synthetic particles with surface active pyridyl moieties and molecularly imprinted cavities for quercetin were prepared via atom transfer radical polymerization. The functionalization of the materials with pyridyl groups was confirmed by FTIR and the SEM micrographs of the hybrid particles demonstrate a clear surface modification compared with the pristine cellulose. Competitive sorption/desorption testing of the imprinted and non‐imprinted particles with standard polyphenols show the achievement of an imprinting factor IF ∼8. Moreover, it was also confirmed the high retention capability of the hybrid materials for polyphenols, due to their strong binding with the surface pyridyl moieties, even when using hydroalcoholic solvents of high ethanol content (e.g., ethanol/water 80/20 v/v). The sorption capabilities of the synthesized materials for polyphenols were explored with the fractionation of flavonols and anthocyanins in winemaking residues. High concentration and enrichment factors were achieved for high‐added value compounds, namely five times for quercetin and 12 for quercetin‐3‐O‐glucuronide with a diatomaceous earth extract and up to 4 for flavonols in a grape pomace (e.g. myricetin and quercetin glucosides). This research demonstrates the feasibility for the combination between the development of engineered materials addressing sustainability with their application to the valorization of agro‐industrial wastes.

Identification of Piperazinyl-Difluoro-indene Derivatives Containing Pyridyl Groups as Potent FGFR Inhibitors against FGFR Mutant Tumor: Design, Synthesis, and Biological Evaluation.

The fibroblast growth factor receptor (FGFR) signaling pathway plays important roles in cellular processes such as proliferation, differentiation, and migration. In this study, we highlighted the potential of FGFR inhibitors bearing the (S)-3,3-difluoro-1-(4-methylpiperazin-1-yl)-2,3-dihydro-1H-indene scaffold containing a crucial 3-pyridyl group for the treatment of FGFR mutant cancers. The representative compound (S)-23, which was identified through comprehensive evaluation, exhibited potent antiproliferative activity with GI50 in the range of 6.4-10.4 nM against FGFR1 fusion protein-carrying, FGFR2-amplified, and FGFR2 mutant cancer cell lines and good antiproliferative activity against FGFR3 translocation and mutant FGFR4 cancer cell lines, as well as potency assessment against FGFR1-4 kinases. Moreover, compound (S)-23 exhibited favorable pharmacokinetic properties, low potential for drug-drug interactions, and very potent antitumor activity in MFE-296 xenograft mouse models with a TGI of 99.1% at the dose of 10 mg/kg. These findings demonstrate that compound (S)-23 is a potential therapeutic agent for FGFR mutant tumors.

Reactions of Cadmium(II) Halides and Di-2-Pyridyl Ketone Oxime: One-Dimensional Coordination Polymers.

The coordination chemistry of 2-pyridyl ketoximes continues to attract the interest of many inorganic chemistry groups around the world for a variety of reasons. Cadmium(II) complexes of such ligands have provided models of solvent extraction of this toxic metal ion from aqueous environments using 2-pyridyl ketoxime extractants. Di-2-pyridyl ketone oxime (dpkoxH) is a unique member of this family of ligands because its substituent on the oxime carbon bears another potential donor site, i.e., a second 2-pyridyl group. The goal of this study was to investigate the reactions of cadmium(II) halides and dpkoxH in order to assess the structural role (if any) of the halogeno ligand and compare the products with their zinc(II) analogs. The synthetic studies provided access to complexes {[CdCl2(dpkoxH)∙2H2O]}n (1∙2H2O), {[CdBr2(dpkoxH)]}n (2) and {[CdI2(dpkoxH)]}n (3) in 50-60% yields. The structures of the complexes were determined by single-crystal X-ray crystallography. The compounds consist of structurally similar 1D zigzag chains, but only 2 and 3 are strictly isomorphous. Neighboring CdII atoms are alternately doubly bridged by halogeno and dpkoxH ligands, the latter adopting the η1:η1:η1:μ (or 2.0111 using Harris notation) coordination mode. A terminal halogeno group completes distorted octahedral coordination at each metal ion, and the coordination sphere of the CdII atoms is {CdII(η1 - X)(μ - X)2(Npyridyl)2(Noxime)} (X = Cl, Br, I). The trans-donor-atom pairs in 1∙2H2O are Clterminal/Noxime and two Clbridging/Npyridyl; on the contrary, these donor-atom pairs are Xterminal/Npyridyl, Xbridging/Noxime, and Xbridging/Npyridyl (X = Br, I). There are intrachain H-bonding interactions in the structures. The packing of the chains in 1∙2H2O is achieved via π-π stacking interactions, while the 3D architecture of the isomorphous 2 and 3 is built via C-H∙∙∙Cg (Cg is the centroid of one pyridyl ring) and π-π overlaps. The molecular structures of 1∙2H2O and 2 are different compared with their [ZnX2(dpkoxH)] (X = Cl, Br) analogs. The polymeric compounds were characterized by IR and Raman spectroscopies in the solid state, and the data were interpreted in terms of the known molecular structures. The solid-state structures of the complexes are not retained in DMSO, as proven via NMR (1H, 13C, and 113Cd NMR) spectroscopy and molar conductivity data. The complexes completely release the coordinated dpkoxH molecule, and the dominant species in solution seem to be [Cd(DMSO)6]2+ in the case of the chloro and bromo complexes and [CdI2(DMSO)4].