Microwave-assisted synthesis, structure, and preliminary biological evaluation of novel 6-methoxy-5,6-dihydro-5-azapurines

Medicinal Chemistr

Regioselective, catalytic 1,1-difluorination of enynes

Fluorinated small molecules are prevalent across the functional small-molecule spectrum, but the scarcity of naturally occurring sources creates an opportunity for creative endeavour in developing routes to access these important materials. Iodine(I)/iodine(III) catalysis has proven to be particularly well-suited to this task, enabling abundant alkene substrates to be readily intercepted by in situ-generated λ3-iodanes and processed to high-value (di)fluorinated products. These organocatalysis paradigms often emulate metal-based processes by engaging the π bond and, in the case of styrenes, facilitating fluorinative phenonium-ion rearrangements to generate difluoromethylene units. Here we demonstrate that enynes are competent proxies for styrenes, thereby mitigating the recurrent need for aryl substituents, and enabling highly versatile homopropargylic difluorides to be generated in an operationally simple manner. The scope of the method is disclosed, together with application in target synthesis (>30 examples, up to >90% yield)

Development of Bicyclo[3.1.0]hexane-based A3 receptor ligands: closing the gaps in the structure–affinity relationships

The adenosine A3 receptor is a promising target for treating and diagnosing inflammation and cancer. In this paper, a series of bicyclo[3.1.0]hexane-based nucleosides was synthesized and evaluated for their P1 receptor affinities in radioligand binding studies. The study focused on modifications at 1-, 2-, and 6-positions of the purine ring and variations of the 5'-position at the bicyclo[3.1.0]hexane moiety, closing existing gaps in the structure-affinity relationships. The most potent derivative 30 displayed moderate A3AR affinity (Ki of 0.38 μM) and high A3R selectivity. A subset of compounds varied at 5'-position was further evaluated in functional P2Y1R assays, displaying no off-target activity.Medicinal Chemistr

Blue-emitting bolaamphiphilic zwitterionic iridium(iii) complex

Aggregation induced emission is a very interesting phenomenon that recently has attracted a lot of interest. Most of the examples deal with organic molecules or flat metal complexes. Here we demonstrate that, by design, even iridium compounds can display this process without shifting the emission energy. In order to enhance the aggregation properties we have focussed on amphiphilic complexes. We report the synthesis and photophysical characterisation of a blue-emitting bolaamphiphilic zwitterionic Ir(iii) complex and an analogous cationic amphiphilic compound, used as a reference. The bolaamphiphile exhibited blue (\u3bbmax = 450 nm) emission in dilute, deaerated solution with a photoluminescence quantum yield (PLQY) of 22%, similar to the related cationic amphiphilic complex. The bolaamphiphile displayed significant emission enhancement in the solid state, with an emission quantum yield that reach 52%. Interestingly, the emission of the cationic analogue suffers from aggregation quenching in the solid state, (PLQY = 3%) as is common for these type of complexes. A correlation between the photophysical data and the arrangement in the solid state is discussed

Tuning the structural and photophysical properties of cationic Pt(II) complexes bearing neutral bis(triazolyl)pyridine ligands

The emission properties of a series of cationic Pt(II) complexes bearing neutral tridentate 2,6-bis-(1H-1,2,3-triazol-5-yl)pyridine and monoanionic ancillary ligands (Cl- or CN-) are described. By varying the substitution pattern on the 1,2,3-triazole moieties of the tridentate luminophore and the nature of the ancillary ligand, we were able to tune the intermolecular interactions between the complexes and therefore the electronic interactions between the metal centers. Indeed, all the compounds possessing Cl- as ancillary ligand are nonluminescent at room temperature, while the complexes containing CN- are luminescent. Interestingly, the \u3c0-accepting nature of this ancillary ligand induces Pt(II)-Pt(II) interactions irrespectively of bulky substitution patterns on the tridentate ligand

Bidentate NHC pyrozolate ligands in luminescent platinum(ii) complexes

A bidentate C^N donor set derived from an N-heterocyclic carbene (NHC) precursor linked to a trifluoromethyl (CF3) functionalized pyrazole ring is described for the first time. The ligands have been employed to prepare four new phosphorescent complexes by the coordination of platinum(ii) centres bearing cyclometalated phenyl-pyridine/triazole-pyridine chelates. The electronic and steric environments of these complexes were tuned through the incorporation of suitable substituents in the phenyl-pyridine/triazole-pyridine ligands, wherein the position of the phenyl-ring substituent (a CF3 group) also directs the selective adoption of either a trans or a cis configuration between the CNHC and the Cphenyl donor atoms. Molecular structures obtained by X-ray diffraction for three of the complexes confirm a distorted square-planar configuration around the platinum centre, and DFT calculations show that the substituents have a significant influence on the energies of the frontier orbitals. Moreover, a platinum(ii) complex featuring the new bidentate NHC^pyrazolate ligand and a bulky adamantyl functionalized pyridine-triazole luminophore was observed to be highly emissive and exhibiting a sky-blue luminescence (\u3bbEm = 470 nm) with photoluminescence quantum yields as high as 50% in doped PMMA matrices. A complete photophysical investigation of all of the complexes in solution as well as in the solid state is herein reported

Diastereodivergent synthesis of enantioenriched α,β-disubstituted-γ-butyrolactones via cooperative N-heterocyclic carbene/Ir catalysis

The stereodivergent synthesis of natural product frameworks via a single transformation using simple starting materials is a significant challenge. The prevalence of γ-butyrolactones in biologically active natural products has long motivated the development of enantioselective strategies towards their synthesis. Herein, we report an enantio- and diastereodivergent [3+2] annulation reaction for the synthesis of α,β-disubstituted γ-butyrolactones through cooperative N-heterocyclic carbene organocatalysis and iridium catalysis. This method overcomes the challenges of merging N-heterocyclic carbene organocatalysis with iridium catalysis by the appropriate choice of ligands. The use of two chiral catalysts allowed control over the relative and absolute configuration of the two formed stereocentres, thereby providing selective access to all four possible stereoisomers of the γ-lactone products. The transformation could be extended to the synthesis of δ-lactams via [4+2] annulation. The synthetic utility of this methodology was illustrated in the concise synthesis of the naturally occurring lignan (−)-hinokinin

Structure-property relationships in aromatic thioethers featuring aggregation-induced emission: Solid-state structures and theoretical analysis

We describe in this paper a structure-property relationship study of aromatic thioethers with aggregation-induced emission (AIE) properties. We combine a structural analysis based on geometrical consideration with an in-depth analysis of the crystalline packing supported by quantum mechanical calculations. Our results allow us to correlate the enhanced fluorescence quantum yields with the significant increase of C-H ef\u3c0 and the decrease of \u3c0 ef\u3c0 interactions in the solid state-a result which supports the well-accepted AIE mechanism quantitatively

Correlating the Structural and Photophysical Features of Pincer Luminophores and Monodentate Ancillary Ligands in Pt-II Phosphors

Phosphorescent PtII complexes featuring pincer luminophores of 2,6-bis(1,2,4-triazolyl)pyridine (H2L1) and 2,6-bis(pyrazolyl)pyridine (H2L3) with a bulky adamantyl or tolyl substituent (H2L4) are systematically compared, and their structural features are correlated with their photophysical properties. The combination with 4-amylpyridine (Py), triphenylphosphine (P) or benzimidazol-2-ylidene (N-heterocyclic carbene, NHC) donors as monodentate ancillary ligands gave a series of highly luminescent triplet emitters with variable aggregation properties. The molecular structures of four of these complexes, namely, Pt-L1-P, Pt-L1-NHC, Pt-L3-P, and Pt-L4-P were garnered from single-crystal X-ray diffraction analysis. The coordination complexes displayed green phosphorescence in solution and in the solid state. In doped poly(methyl methacrylate) (PMMA) matrices, most of the complexes exhibited high phosphorescence quantum yields, which reached 59 % for Pt-L3-P. A comparative analysis between the spectroscopic data and the computed parameters derived from time-dependent density functional theory (TD-DFT) calculations suggests that the emission originates from metal-perturbed ligand-centered excited triplet states (3MP-LC). The radiationless deactivation rate constants of the emissive states can be correlated with the aggregation properties derived from the substitution pattern at the tridentate luminophores and the ancillary ligands, whereas the radiative rate constants are determined by the electronic structures of the complexes. We found that PtII complexes containing pyrazolate donors showed an enhanced charge-transfer character in the excited state, whereas bulky adamantyl moieties and triphenylphosphine ancillary ligands suppress bimolecular aggregation and quenching phenomena