Substituted aromatic pentaphosphole ligands – a journey across the p-block

The functionalization of pentaphosphaferrocene [Cp*Fe(η⁵-P₅)] (1) with cationic group 13–17 electrophiles is shown to be a general synthetic strategy towards P–E bond formation of unprecedented diversity. The products of these reactions are dinuclear [{Cp*Fe}₂{μ,η^5:5-(P₅)₂EX₂}][TEF] (EX₂ = BBr₂ (2), GaI₂ (3), [TEF]⁻ = [Al{OC(CF₃)₃}₄]⁻) or mononuclear [Cp*Fe(η⁵-P₅E)][X] (E = CH₂Ph (4), CHPh₂ (5), SiHPh₂ (6), AsCy₂ (7), SePh (9), TeMes (10), Cl (11), Br (12), I (13)) complexes of hetero-bis-pentaphosphole ((cyclo-P₅)₂R) or hetero-pentaphosphole ligands (cyclo-P₅R), the aromatic all-phosphorus analogs of prototypical cyclopentadienes. Further, modifying the steric and electronic properties of the electrophile has a drastic impact on its reactivity and leads to the formation of [Cp*Fe(μ,η^5:2-P₅)SbICp′′′][TEF] (8) which possesses a triple-decker-like structure. X-ray crystallographic characterization reveals the slightly twisted conformation of the cyclo-P₅R ligands in these compounds and multinuclear NMR spectroscopy confirms their integrity in solution. DFT calculations shed light on the bonding situation of these compounds and confirm the aromatic character of the pentaphosphole ligands on a journey across the p-block.

The reactivity of cationic electrophiles towards pentaphosphaferrocene [Cp*Fe(ƞ⁵-P₅)] is explored. We report P–E bond formation for electrophiles across the p-block, producing coordination complexes with unprecedented hetero-bispentaphosphole and hetero-pentaphosphole ligands.     

Zweikernige Palladium(II)‐, Platin(II)‐ und Iridium(III)‐Komplexe von Bis[imidazol‐4‐yl]alkanen

Dinuclear Palladium(II), Platinum(II), and Iridium(III) Complexes of Bis[imidazol‐4‐yl]alkanes The reaction of bis(1,1′‐triphenylmethyl‐imidazol‐4‐yl) alkanes ((CH₂)_n bridged imidazoles L(CH₂)_nL, n = 3–6) with chloro bridged complexes [R₃P(Cl)M(μ‐Cl)M(Cl)PR₃] (M = Pd, Pt; R = Et, Pr, Bu) affords the dinuclear compounds [Cl₂(R₃P)M–L(CH₂)_nL–M(PR₃)Cl₂] 1 – 17 . The structures of [Cl₂(Et₃P)Pd–L(CH₂)₃L–Pd(PEt₃)Cl₂] ( 1 ), [Cl₂(Bu₃P)Pd–L(CH₂)₄L–Pd(PBu₃)Cl₂] ( 10 ), [Cl₂(Et₃P)Pd–L(CH₂)₅L–Pd(PEt₃)Cl₂] ( 3 ), [Cl₂(Et₃P)Pt–L(CH₂)₃L–Pt(PEt₃)Cl₂] ( 13 ) with trans Cl–M–Cl groups were determined by X‐ray diffraction. Similarly the complexes [Cl₂(Cp*)Ir–L(CH₂)_nL–Ir(Cp*)Cl₂] (n = 4–6) are obtained from [Cp*(Cl)Ir(μ‐Cl)₂Ir(Cl)Cp*] and the methylene bridged bis(imidazoles).     

Ni(0)-promoted activation of Csp2–H and Csp2–O bonds

A dinickel(0)–N₂ complex, stabilized with a rigid acridane-based PNP pincer ligand, was studied for its ability to activate C(sp²)–H and C(sp²)–O bonds. Stabilized by a Ni–μ–N₂–Na⁺ interaction, it activates C–H bonds of unfunctionalized arenes, affording nickel–aryl and nickel–hydride products. Concomitantly, two sodium cations get reduced to Na(0), which was identified and quantified by several methods. Our experimental results, including product analysis and kinetic measurements, strongly suggest that this C(sp²)–H activation does not follow the typical oxidative addition mechanism occurring at a low-valent single metal centre. Instead, via a bimolecular pathway, two powerfully reducing nickel ions cooperatively activate an arene C–H bond and concomitantly reduce two Lewis acidic alkali metals under ambient conditions. As a novel synthetic protocol, nickel(ii)–aryl species were directly synthesized from nickel(ii) precursors in benzene or toluene with excess Na under ambient conditions. Furthermore, when the dinickel(0)–N₂ complex is accessed via reduction of the nickel(ii)–phenyl species, the resulting phenyl anion deprotonates a C–H bond of glyme or 15-crown-5 leading to C–O bond cleavage, which produces vinyl ether. The dinickel(0)–N₂ species then cleaves the C(sp²)–O bond of vinyl ether to produce a nickel(ii)–vinyl complex. These results may provide a new strategy for the activation of C–H and C–O bonds mediated by a low valent nickel ion supported by a structurally rigidified ligand scaffold.

A structurally rigidified nickel(0) complex was found to be capable of cleaving both C(sp²)–H and C(sp²)–O bonds.     

Structure,Z′ = 2 Crystal Packing Features of 3-(2-Chlorobenzylidene)-5-(p-tolyl)furan-2(3H)-one

3-(2-Chlorobenzylidene)-5-(p-tolyl)furan-2(3H)-one (1), C₁₈H₁₃ClO₂, crystallizes with Z = 8 and Z′ = 2, and the structure at 100 K has orthorhombic (Pna2₁) symmetry. Each kind of molecule takes part in π–π stacking interactions to form infinite chains parallel to the c axis. We believe that the existence of two forms can be explained by the probable rotation around a single C–C bond. The quantum chemical modeling reveals that these molecules are almost equivalent energetically, and they can be described as the two most stable conformers (rotamers) with a minor rotational barrier of about 0.67 kcal/mol.     

Half‐Sandwich Iridium Complexes Bearing a Diprotic Glyoxime Ligand: Structural Diversity Induced by Reversible Deprotonation

Synthesis and deprotonation reactions of half‐sandwich iridium complexes bearing a vicinal dioxime ligand were studied. Treatment of [{Cp*IrCl(μ‐Cl)}₂] (Cp*=η⁵‐C₅Me₅) with dimethylglyoxime (LH₂) at an Ir:LH₂ ratio of 1:1 afforded the cationic dioxime iridium complex [Cp*IrCl(LH₂)]Cl ( 1 ). The chlorido complex 1 undergoes stepwise and reversible deprotonation with potassium carbonate to give the oxime–oximato complex [Cp*IrCl(LH)] ( 2 ) and the anionic dioximato(2?) complex K[Cp*IrCl(L)] ( 3 ) sequentially. Meanwhile, twofold deprotonation of the sulfato complex [Cp*Ir(SO₄)(LH₂)] ( 4 ) resulted in the formation of the oximato‐bridged dinuclear complex [{Cp*Ir(μ‐L)}₂] ( 5 ). X‐ray analyses disclosed their supramolecular structures with one‐dimensional infinite chain ( 1 and 2 ), hexagonal open channels ( 3 ), and a tetrameric rhomboid ( 4 ) featuring multiple intermolecular hydrogen bonds and electrostatic interactions.     

2′-O-Trifluoromethylated RNA – a powerful modification for RNA chemistry and NMR spectroscopy

New RNA modifications are needed to advance our toolbox for targeted manipulation of RNA. In particular, the development of high-performance reporter groups facilitating spectroscopic analysis of RNA structure and dynamics, and of RNA–ligand interactions has attracted considerable interest. To this end, fluorine labeling in conjunction with ¹⁹F-NMR spectroscopy has emerged as a powerful strategy. Appropriate probes for RNA previously focused on single fluorine atoms attached to the 5-position of pyrimidine nucleobases or at the ribose 2′-position. To increase NMR sensitivity, trifluoromethyl labeling approaches have been developed, with the ribose 2′-SCF₃ modification being the most prominent one. A major drawback of the 2′-SCF₃ group, however, is its strong impact on RNA base pairing stability. Interestingly, RNA containing the structurally related 2′-OCF₃ modification has not yet been reported. Therefore, we set out to overcome the synthetic challenges toward 2′-OCF₃ labeled RNA and to investigate the impact of this modification. We present the syntheses of 2′-OCF₃ adenosine and cytidine phosphoramidites and their incorporation into oligoribonucleotides by solid-phase synthesis. Importantly, it turns out that the 2′-OCF₃ group has only a slight destabilizing effect when located in double helical regions which is consistent with the preferential C3′-endo conformation of the 2′-OCF₃ ribose as reflected in the ³J (H1′–H2′) coupling constants. Furthermore, we demonstrate the exceptionally high sensitivity of the new label in ¹⁹F-NMR analysis of RNA structure equilibria and of RNA–small molecule interactions. The study is complemented by a crystal structure at 0.9 Å resolution of a 27 nt hairpin RNA containing a single 2′-OCF₃ group that well integrates into the minor groove. The new label carries high potential to outcompete currently applied fluorine labels for nucleic acid NMR spectroscopy because of its significantly advanced performance.

The new 2′-OCF₃ label for nucleic acid NMR spectroscopy carries high potential to outcompete currently applied fluorine labels because of significantly advanced performance.     

2,2′-Bipyridyl formation from 2-arylpyridines through bimetallic diyttrium intermediate

An alkylyttrium complex supported by an N,N′-bis(2,6-diisopropylphenyl)ethylenediamido ligand, (ArNCH₂CH₂NAr)Y(CH₂SiMe₃)(THF)₂ (1, Ar = 2,6-ⁱPr₂C₆H₃), activated an ortho-phenyl C–H bond of 2-phenylpyridine (2a) to form a (2-pyridylphenyl)yttrium complex (3a) containing a five-membered metallacycle. Subsequently, a unique C(sp²)–C(sp²) coupling of 2-phenylpyridine proceeded through a bimetallic yttrium intermediate, derived from an intramolecular shift of the yttrium center to an ortho-position of the pyridine ring in 3a, to yield a bimetallic yttrium complex (4a) bridged by two-electron reduced 6,6′-diphenyl-2,2′-bipyridyl. Aryl substituents at the ortho-position of the pyridine ring were key in order to destabilize the μ,κ²-(C,N)-pyridyldiyttrium intermediate prior to the C(sp²)–C(sp²) bond formation.     

In silico design to enhance the barrier height for magnetization reversal in Dy(iii) sandwich complexes by stitching them under the umbrella of corannulene

Lanthanide based single molecular magnets (SMMs), particularly dysprocenium based SIMs, are well known for their high energy barrier for spin reversal (U_eff) and blocking temperatures (T_B). Enhancing these two parameters and at the same time obtaining ambient stability is key to realising end-user applications such as compact storage or as qubits in quantum computing. In this work, by employing an array of theoretical tools (DFT, ab initio CASSCF and molecular dynamics), we have modelled six complexes [(η⁵-corannulene)Dy(Cp)] (1), [(η⁵-corannulene)Dy(C₆H₆)] (2), [(η⁶-corannulene)Dy(Cp)] (3), [(η⁶-corannulene)Dy(C₆H₆)] (4), [(exo-η⁵-corannulene)Dy(endo-η⁵-corannulene)] (5), and [(endo-η⁵-corannulene)Dy(endo-η⁵-corannulene)] (6) containing corannulene as a capping ligand to stabilise Dy(iii) half-sandwich complexes. Our calculations predict a strong axiality exerted by the Dy–C interactions in all complexes. Ab initio calculations predict a very large barrier height for all six molecules in the order 1 (919 cm⁻¹) ≈ 3 (913 cm⁻¹) > 2 (847 cm⁻¹) > 4 (608 cm⁻¹) ≈ 5 (603 cm⁻¹) ≈ 6 (599 cm⁻¹), suggesting larger barrier heights for Cp ring systems, followed by six-membered arene systems and then corannulene. DFT based molecular dynamics calculations were performed on complexes 3, 5 and 6. For complexes 3 and 5, the geometries that are dynamically accessible are far fewer. The range of U_eff computed for molecular dynamics snapshots is high, indicating a possibility of translating the large U_eff obtained into attractive blocking temperatures in these complexes, but the converse is found for 6. Furthermore, an in-depth C–H bond vibrational analysis performed on complex 3 suggests that the vibration responsible for reducing the blocking temperature in dysprocenium SIMs is absent here as the C–H bonds are stronger and corannulene steric strain prevents the C(Cp)–Dy–C(Cor) bending. As [(η⁶-corannulene)TM(X)]⁺ (TM = Ru, Zr, Os, Rh, Ir and X = C₅Me₅, C₆Me₆) are known, the predictions made here have a higher prospect of yielding stability under ambient conditions, a very large U_eff value and a high blocking temperature – a life-giving combination to new generation SMMs.

Bringing half-sandwich Dy(iii) SIMs under the umbrella of corannulene was found to offer stability, greater barrier height and may offer higher blocking temperatures.     

The use of half-sandwich iridium dithiolate and diselenolate complexes, Cp*Ir(L)(ER)2 (L=CO, PMe3, PPh3; ER=SPh, SePh, SeMe), for the synthesis of heterodimetallic compounds. The molecular structure of Cp*Ir(CO)(μ-SePh)2[Mo(CO)4]

Carbonyl–iridium half-sandwich compounds, Cp*Ir(CO)(EPh)₂ (E=S, Se), were prepared by the photo-induced reaction of Cp*Ir(CO)₂ with the diphenyl dichalcogenides, E₂Ph₂, and used as neutral chelating ligands in carbonylmetal complexes such as Cp*Ir(CO)(μ-EPh)₂[Cr(CO)₄], Cp*Ir(CO)(μ-EPh)₂[Mo(CO)₄] and Cp*Ir(CO)(μ-EPh)₂[Fe(CO)₃], respectively. A trimethylphosphane–iridium analogue, Cp*Ir(PMe₃)(μ-SeMe)₂[Cr(CO)₄], was also obtained. The new heterodimetallic complexes were characterized by IR and NMR spectroscopy, and the molecular geometry of Cp*Ir(CO)(μ-SePh)₂[Mo(CO)₄] has been determined by a single crystal X-ray structure analysis. According to the long Ir…Mo distance (395.3(1) Å), direct metal–metal interactions appear to be absent.     

Structural diversity of mixed polypnictogen complexes: dicationic E2E′2 (E ≠ E′ = P,As, Sb,Bi) chains,cycles and cages stabilized by transition metals

The reactivity of the tetrahedral dipnictogen complexes [{CpMo(CO)₂}₂(μ,η²:η²-EE′)] (E, E′ = P, As, Sb, Bi; “Mo₂EE′”) towards different one-electron oxidation agents is reported. Oxidation with [Thia][TEF] (Thia⁺ = C₁₂H₈S₂⁺; TEF⁻ = Al{OC(CF₃)₃}₄⁻) leads to the selective formation of the radical monocations [Mo₂EE′]˙⁺, which immediately dimerize to the unprecedented dicationic E₂E′₂ ligand complexes [{CpMo(CO)₂}₄(μ₄,η²:η²:η²:η²-E′EEE′)]²⁺via E–E bond formation. Single crystal X-ray diffraction revealed that, in the case of Mo₂PAs and Mo₂PSb, P–P bond formation occurs yielding zigzag E₂P₂ (E = As (1), Sb (2)) chains, whereas Mo₂SbBi forms a Sb₂Bi₂ (5) cage, Mo₂AsSb an unprecedented As₂Sb₂ unit representing an intermediate stage between a chain- and a cage-type structure, and Mo₂AsBi a novel planar As₂Bi₂ (4a) cycle. Therefore, 1–5 bear the first substituent-free, dicationic hetero-E₄ ligands, stabilized by transition metal fragments. Furthermore, in the case of Mo₂AsSb, the exchange of the counterion causes changes in the molecular structure yielding an unusual, cyclic As₂Sb₂ ligand. The experimental results are corroborated by DFT calculations.

Unique dicationic hetero-tetrapnictogen E₂E′₂ (E ≠ E′ = P, As, Sb, Bi) chains and cages are obtained via oxidation of the tetrahedranes [{CpMo(CO)₂}₂(μ,η²:η²-EE′)]. Exchange of the counterion causes an unusual cyclization of the As₂Sb₂ ligand.     

η-Pentamethylcyclopentadienylruthenium(II) complexes containing η-coordinated α-amino acids

Reaction of [Cp* RuCl₂]₂ with -alanine ( -alaH) in methanol at room temperature in the presence of NaOMe yields the complex Na[Cp* RuCl( -ala)] (1), which contains a five-membered N,O-coordinated chelate ring. The analogous complex Na[Cp* RuCl( -phe)] (2) is obtained under similar conditions but at 0°C in 90% yield. At temperatures above 20°C both 2 and the η⁶-coordinated complex [Cp* Ru( -pheH)]Cl (4) are obtained, with the proportion of the latter increasing with temperature. Compound 4 is obtained in 88% yield by refluxing [Cp* RuCl₂]₂ and -phenylalanine ( -pheH) in CH₃OH/CH₃ONa followed by separation from 2. The analogous ruthenium(II) sandwich complexes 5–10 were obtained from -tyrosine and -tryptophane and various derivatives. [Cp* Ru( -met)] (3), prepared by the reaction of [Cp* RuCl₂]₂ with -methionine ( -metH) in CH₃OH/CH₃ONa, displays N,O,S-coordination.     

Crystallographic report: The [bis(η5‐methylcyclopentadienyl)titanium(IV)‐bis(N‐methylglycine)] dichloride

The crystal network of [Cp′₂Ti(N?CH₃? Gly)₂]²⁺[Cl^?]₂ (Cp′ = (CH₃)C₅H₄) complex, which crystallizes as a solvate with CH₃OH, is built up with discrete cationic units connected through intermolecular H· · ·Cl bonds. The α‐amino acid ligands are attached through an intramolecular H· · ·O bond within one cationic unit. Copyright © 2004 John Wiley & Sons, Ltd.     

Exploring benzylic gem-C(sp3)–boron–silicon and boron–tin centers as a synthetic platform

A stepwise build-up of multi-substituted C_sp³ carbon centers is an attractive, conceptually simple, but often synthetically challenging type of disconnection. To this end, this report describes how gem-α,α-dimetalloid-substituted benzylic reagents bearing boron/silicon or boron/tin substituent sets are an excellent stepping stone towards diverse substitution patterns. These gem-dimetalloids were readily accessed, either by known carbenoid insertion into C–B bonds or by the newly developed scalable deprotonation/metallation approach. Highly chemoselective transformations of either the C–Si (or C–Sn) or the C–B bonds in the newly formed gem-C_sp³ centers have been achieved through a set of approaches, with a particular focus on exploiting the synthetically versatile polarity reversal in organometalloids by λ³-aryliodanes. Of particular note is the metal-free arylation of the C–Si (or C–Sn) bonds in such gem-dimetalloids via the iodane-guided C–H coupling approach. DFT calculations show that this transfer of the (α-Bpin)benzyl group proceeds via unusual [5,5]-sigmatropic rearrangement and is driven by the high-energy iodine(iii) center. As a complementary tool, the gem-dimetalloid C–B bond is shown to undergo a potent and chemoselective Suzuki–Miyaura arylation with diverse Ar–Cl, thanks to the development of the reactive gem-α,α-silyl/BF₃K building blocks.

This work explores divergent reactivity of the benzylic gem-boron–silicon and boron–tin double nucleophiles, including the arylation of the C–B bond with Ar–Cl, along with a complementary oxidative λ³-iodane-guided arylation of the C–Si/Sn moiety.     

Bis(dicarbollide) Complexes of Transition Metals as a Platform for Molecular Switches. Study of Complexation of 8,8′-Bis(methylsulfanyl) Derivatives of Cobalt and Iron Bis(dicarbollides)

Complexation of the 8,8′-bis(methylsulfanyl) derivatives of cobalt and iron bis(dicarbollides) [8,8′-(MeS)₂-3,3′-M(1,2-C₂B₉H₁₀)₂]⁻ (M = Co, Fe) with copper, silver, palladium and rhodium leads to the formation of the corresponding chelate complexes, which is accompanied by a transition from the transoid to the cisoid conformation of the bis(dicarbollide) complex. This transition is reversible and can be used in design of coordination-driven molecular switches based on transition metal bis(dicarbollide) complexes. The solid-state structures of {(Ph₃P)ClPd[8,8′- (MeS)₂-3,3′-Co(1,2-C₂B₉H₁₀)₂-κ²-S,S′]} and {(COD)Rh[8,8′-(MeS)₂-3,3′-Co(1,2-C₂B₉H₁₀)₂-κ²-S,S′]} were determined by single crystal X-ray diffraction.     

Transformation of a Cp*–Iridium(III) Precatalyst for Water Oxidation when Exposed to Oxidative Stress

The reaction of [Cp*Ir(bzpy)NO₃] ( 1 ; bzpy=2‐benzoylpyridine, Cp*=pentamethylcyclopentadienyl anion), a competent water‐oxidation catalyst, with several oxidants (H₂O₂, NaIO₄, cerium ammonium nitrate (CAN)) was studied to intercept and characterize possible intermediates of the oxidative transformation. NMR spectroscopy and ESI‐MS techniques provided evidence for the formation of many species that all had the intact Ir–bzpy moiety and a gradually more oxidized Cp* ligand. Initially, an oxygen atom is trapped in between two carbon atoms of Cp* and iridium, which gives an oxygen–Ir coordinated epoxide, whereas the remaining three carbon atoms of Cp* are involved in a η³ interaction with iridium ( 2 a ). Formal addition of H₂O to 2 a or H₂O₂ to 1 leads to 2 b , in which a double MeCOH functionalization of Cp* is present with one MeCOH engaged in an interaction with iridium. The structure of 2 b was unambiguously determined in the solid state and in solution by X‐ray single‐crystal diffractometry and advanced NMR spectroscopic techniques, respectively. Further oxidation led to the opening of Cp* and transformation of the diol into a diketone with one carbonyl coordinated at the metal ( 2 c ). A η³ interaction between the three non‐oxygenated carbons of “ex‐Cp*” and iridium is also present in both 2 b and 2 c . Isolated 2 b and mixtures of 2 a – c species were tested in water‐oxidation catalysis by using CAN as sacrificial oxidant. They showed substantially the same activity than 1 (turnover frequency values ranged from 9 to 14 min^?1).     

Temperature-modulated selective C(sp3)–H or C(sp2)–H arylation through palladium catalysis

Transition metal-catalysed C–H bond functionalisations have been extensively developed in organic and medicinal chemistry. Among these catalytic approaches, the selective activation of C(sp³)–H and C(sp²)–H bonds is particularly appealing for its remarkable synthetic versatility, yet it remains highly challenging. Herein, we demonstrate the first example of temperature-dependent selective C–H functionalisation of unactivated C(sp³)–H or C(sp²)–H bonds at remote positions through palladium catalysis using 7-pyridyl-pyrazolo[1,5-a]pyrimidine as a new directing group. At 120 °C, C(sp³)–H arylation was triggered by the chelation of a rare [6,5]-fused palladacycle, whereas at 140 °C, C(sp²)–H arylation proceeded instead through the formation of a 16-membered tetramer containing four 7-pyridyl-pyrazolo[1,5-a]pyrimidine–palladium chelation units. The subsequent mechanistic study revealed that both C–H activations shared a common 6-membered palladacycle intermediate, which was then directly transformed to either the [6,5]-fused palladacycle for C(sp³)–H activation at 120 °C or the tetramer for C(sp²)–H arylation at 140 °C with catalytic amounts of Pd(OAc)₂ and AcOH. Raising the temperature from 120 °C to 140 °C can also convert the [6,5]-fused palladacycle to the tetramer with the above-mentioned catalysts, hence completing the C(sp²)–H arylation ultimately.

Unprecedented 16-membered tetramer or [6,5]-fused palladacycle, mutually shadowboxing-like transformed from the shared common intermediate, accomplishes the Pd-catalysed temperature-dependent selective arylation of C(sp²)–H or C(sp³)–H.     

Lysosome‐targeted potent half‐sandwich iridium(III) α‐diimine antitumor complexes

Fifteen organometallic Ir(III) half‐sandwich complexes ( 1A – 5C ) having the general formula [(η⁵‐Cp^x)Ir(N^N)Cl]PF₆ (Cp^x = Cp*, tetramethyl(phenyl)cyclopentadienyl (Cp^xph) or tetramethyl(biphenyl)cyclopentadienyl (Cp^xbiph); N^N = diamine) have been synthesized and characterized. The molecular structure of 1A was determined using single‐crystal X‐ray diffraction analysis. The hydrolysis of 1A – 5C was monitored using UV–visible spectra. Complexes 3A – 3C showed catalytic activity for the oxidation of NADH to NAD⁺, where 3C showed the highest turnover number of 29.9 within 450 min. Cytotoxicity examination by MTT assay was carried out against two human cancer cell lines (HeLa and A549) after 24 or 48 h drug treatment. The complexes showed high potency, where the most potent complex ( 3C ; IC₅₀ = 3.4 μM) was six times more active than cisplatin against A549 cells after 24 h drug exposure. Cytotoxic potency towards A549 cells increased with phenyl substitution on Cp ring: Cp^xbiph > Cp^xph > Cp*. In addition, the biological studies showed that 3C caused cell apoptosis and cell cycle arrest at G₁ phase in A549 cancer cells. Moreover, 3C increased the level of reactive oxygen species markedly after 24 h, which may provide an important basis for killing cancer cells. Confocal laser scanning microscopy was used to track 3C in A549 cells. The cellular localization experiment showed that 3C targeted lysosomes and caused lysosomal damage.     

Convenient Synthesis of Pyrazolo[4′,3′:5,6]pyrano[4,3-c][1,2]oxazoles via Intramolecular Nitrile Oxide Cycloaddition

A simple and efficient synthetic route to the novel 3a,4-dihydro-3H,7H- and 4H,7H-pyrazolo[4′,3′:5,6]pyrano[4,3-c][1,2]oxazole ring systems from 3-(prop-2-en-1-yloxy)- or 3-(prop-2-yn-1-yloxy)-1H-pyrazole-4-carbaldehyde oximes has been developed by employing the intramolecular nitrile oxide cycloaddition (INOC) reaction as the key step. The configuration of intermediate aldoximes was unambiguously determined using NOESY experimental data and comparison of the magnitudes of ¹J_CH coupling constants of the iminyl moiety, which were greater by approximately 13 Hz for the predominant syn isomer. The structures of the obtained heterocyclic products were confirmed by detailed ¹H, ¹³C and ¹⁵N NMR spectroscopic experiments and HRMS measurements.     

Visible light driven deuteration of formyl C–H and hydridic C(sp3)–H bonds in feedstock chemicals and pharmaceutical molecules

Deuterium labelled compounds are of significant importance in chemical mechanism investigations, mass spectrometric studies, diagnoses of drug metabolisms, and pharmaceutical discovery. Herein, we report an efficient hydrogen deuterium exchange reaction using deuterium oxide (D₂O) as the deuterium source, enabled by merging a tetra-n-butylammonium decatungstate (TBADT) hydrogen atom transfer photocatalyst and a thiol catalyst under light irradiation at 390 nm. This deuteration protocol is effective with formyl C–H bonds and a wide range of hydridic C(sp³)–H bonds (e.g. α-oxy, α-thioxy, α-amino, benzylic, and unactivated tertiary C(sp³)–H bonds). It has been successfully applied to the high incorporation of deuterium in 38 feedstock chemicals, 15 pharmaceutical compounds, and 6 drug precursors. Sequential deuteration between formyl C–H bonds of aldehydes and other activated hydridic C(sp³)–H bonds can be achieved in a selective manner.

A selective hydrogen deuterium exchange reaction with formyl C–H bonds and a wide range of hydridic C(sp³)–H bonds has been achieved by merging tetra-n-butylammonium decatungstate photocatalyst and a thiol catalyst under 390 nm light irradiation.     

Controlled-Potential Coulometric Determination of Iridium in Hexanitroiridate(III) with Microwave Sample Preparation

A procedure is proposed for determining 0.40 to 7.00 mg of iridium (RSD = 1–4%) in Ir(NO₂)^3- ₆. The procedure involved the fast conversion of Ir(NO₂)^3- ₆ into IrCl^2- ₆ by heating it with an HCl solution in a microwave oven and the controlled-potential coulometric determination of iridium using the Ir(IV)/Ir(III) redox system.