Complexation and redox chemistry of neptunium,plutonium and americium with a hydroxylaminato ligand

There is significant interest in ligands that can stabilize actinide ions in oxidation states that can be exploited to chemically differentiate 5f and 4f elements. Applications range from developing large-scale actinide separation strategies for nuclear industry processing to carrying out analytical studies that support environmental monitoring and remediation efforts. Here, we report syntheses and characterization of Np(iv), Pu(iv) and Am(iii) complexes with N-tert-butyl-N-(pyridin-2-yl)hydroxylaminato, [2-(^tBuNO)py]⁻(interchangeable hereafter with [(^tBuNO)py]⁻), a ligand which was previously found to impart remarkable stability to cerium in the +4 oxidation state. An[(^tBuNO)py]₄ (An = Pu, 1; Np, 2) have been synthesized, characterized by X-ray diffraction, X-ray absorption, ¹H NMR and UV-vis-NIR spectroscopies, and cyclic voltammetry, along with computational modeling and analysis. In the case of Pu, oxidation of Pu(iii) to Pu(iv) was observed upon complexation with the [(^tBuNO)py]⁻ ligand. The Pu complex 1 and Np complex 2 were also isolated directly from Pu(iv) and Np(iv) precursors. Electrochemical measurements indicate that a Pu(iii) species can be accessed upon one-electron reduction of 1 with a large negative reduction potential (E_1/2 = −2.26 V vs. Fc^+/0). Applying oxidation potentials to 1 and 2 resulted in ligand-centered electron transfer reactions, which is different from the previously reported redox chemistry of U^IV[(^tBuNO)py]₄ that revealed a stable U(v) product. Treatment of an anhydrous Am(iii) precursor with the [(^tBuNO)py]⁻ ligand did not result in oxidation to Am(iv). Instead, the dimeric complex [Am^III(μ₂-(^tBuNO)py)((^tBuNO)py)₂]₂ (3) was isolated. Complex 3 is a rare example of a structurally characterized non-aqueous Am-containing molecular complex prepared using inert atmosphere techniques. Predicted redox potentials from density functional theory calculations show a trivalent accessibility trend of U(iii) < Np(iii) < Pu(iii) and that the higher oxidation states of actinides (i.e., +5 for Np and Pu and +4 for Am) are not stabilized by [2-(^tBuNO)py]⁻, in good agreement with experimental observations.

The coordination modes and electronic properties of a strongly coordinating hydroxylaminato ligand with Np, Pu and Am were investigated.Complexes were characterized by a range of experimental and computational techniques.     

Enantiomeric β-sheet peptides from Aβ form homochiral pleated β-sheets rather than heterochiral rippled β-sheets

In 1953, Pauling and Corey postulated “rippled” β-sheets, composed of a mixture of d- and l-peptide strands, as a hypothetical alternative to the now well-established structures of “pleated” β-sheets, which they proposed as a component of all-l-proteins. Growing interest in rippled β-sheets over the past decade has led to the development of mixtures of d- and l-peptides for biomedical applications, and a theory has emerged that mixtures of enantiomeric β-sheet peptides prefer to co-assemble in a heterochiral fashion to form rippled β-sheets. Intrigued by conflicting reports that enantiomeric β-sheet peptides prefer to self-assemble in a homochiral fashion to form pleated β-sheets, we set out address this controversy using two β-sheet peptides derived from Aβ_17–23 and Aβ_30–36, peptides 1a and 1b. Each of these peptides self-assembles to form tetramers comprising sandwiches of β-sheet dimers in aqueous solution. Through solution-phase NMR spectroscopy, we characterize the different species formed when peptides 1a and 1b are mixed with their respective d-enantiomers, peptides ent-1a and ent-1b. ¹H NMR, DOSY, and ¹H,¹⁵N-HSQC experiments reveal that mixing peptides 1a and ent-1a results in the predominant formation of homochiral tetramers, with a smaller fraction of a new heterochiral tetramer, and mixing peptides 1b and ent-1b does not result in any detectable heterochiral assembly. ¹⁵N-edited NOESY reveals that the heterochiral tetramer formed by peptides 1a and ent-1a is composed of two homochiral dimers. Collectively, these NMR studies of Aβ-derived peptides provide compelling evidence that enantiomeric β-sheet peptides prefer to self-assemble in a homochiral fashion in aqueous solution.

In aqueous solution, mixtures of l- and d- macrocyclic β-sheet peptides derived from Aβ self-assemble to form homochiral pleated β-sheets but do not co-assemble to form heterochiral rippled β-sheets.     

Organocopper(ii) complexes: new catalysts for carbon–carbon bond formation via electrochemical atom transfer radical addition (eATRA)

Organocopper(ii) complexes are a rarity while organocopper(i) complexes are commonplace in chemical synthesis. In the course of building a strategy to generate organocopper(ii) species utilizing electrochemistry, a method to form compounds with Cu^II–C bonds was discovered, that demonstrated remarkably potent reactivity towards different functionalized alkenes under catalytic control. The role of the organocopper(ii) complex is to act as a source of masked radicals (in this case ˙CH₂CN) that react with an alkene to generate the corresponding γ-halonitrile in good yields through atom transfer radical addition (ATRA) to various alkenes. The organocopper(ii) complexes can be continuously regenerated electrochemically for ATRA (eATRA), which proceeds at room temperature, under low Cu loadings (1–10 mol%) and with the possibility of Cu-catalyst recovery.

Electrochemical generation of a novel organocopper(ii) complex offers a new way to carry out atom transfer radical addition to alkenes under mild conditions with high yields and low catalyst loadings.     

Hemilabile MIC^N ligands allow oxidant-free Au(i)/Au(iii) arylation-lactonization of γ-alkenoic acids

Oxidant-free Au-catalyzed reactions are emerging as a new synthetic tool for innovative organic transformations. Oxidant-free Au-catalyzed reactions are emerging as a new synthetic tool for innovative organic transformations. Still, a deeper mechanistic understanding is needed for a rational design of these processes. Here we describe the synthesis of two Au(i) complexes bearing bidentated hemilabile MIC^N ligands, [Au^I(MIC^N)Cl], and their ability to stabilize square-planar Au(iii) species (MIC = mesoionic carbene). The presence of the hemilabile N-ligand contributed to stabilize the ensuing Au(iii) species acting as a five-membered ring chelate upon its coordination to the metal center. The Au(iii) complexes can be obtained either by using external oxidants or, alternatively, by means of feasible oxidative addition with strained biphenylene C_sp²–C_sp² bonds as well as with aryl iodides. Based on the fundamental knowledge gained on the redox properties on these Au(i)/Au(iii) systems, we successfully develop a novel Au(i)-catalytic procedure for the synthesis of γ-substituted γ-butyrolactones through the arylation-lactonization reaction of the corresponding γ-alkenoic acid. The oxidative addition of the aryl iodide, which in turn is allowed by the hemilabile nature of the MIC^N ligand, is an essential step for this transformation.

A novel hemilabile MIC^N ligand-based Au(i)-catalytic procedure for the synthesis of γ-substituted γ-butyrolactones through the arylation-lactonization reaction of the corresponding γ-alkenoic acid is presented.     

Two Natural Flavonoid Substituted Polysaccharides from Tamarix chinensis: Structural Characterization and Anticomplement Activities

Two novel natural flavonoid substituted polysaccharides (MBAP-1 and MBAP-2) were obtained from Tamarix chinensis Lour. and characterized by HPGPC, methylation, ultra-high-performance liquid chromatography-ion trap tandem mass spectrometry (UPLC-IT-MSⁿ), and NMR analysis. The results showed that MBAP-1 was a homogenous heteropolysaccharide with a backbone of 4)-β-d-Glcp-(1→ and →3,4,6)-β-d-Glcp-(1→. MBAP-2 was also a homogenous polysaccharide which possessed a backbone of →3)-α-d-Glcp-(1→, →4)-β-d-Glcp-(1→ and →3,4)-β-d-Glcp-2-OMe-(1→. Both the two polysaccharides were substituted by quercetin and exhibited anticomplement activities in vitro. However, MBAP-1 (CH₅₀: 0.075 ± 0.004 mg/mL) was more potent than MBAP-2 (CH₅₀: 0.249 ± 0.006 mg/mL) and its reduced product, MBAP-1R (CH₅₀: 0.207 ± 0.008 mg/mL), indicating that multiple monosaccharides and uronic acids might contribute to the anticomplement activity of the flavonoid substituted polysaccharides of T. chinensis. Furthermore, the antioxidant activity of MBAP-1 was also more potent than that of MBAP-2. In conclusion, these two flavonoid substituted polysaccharides from T. chinensis were found to be potential oxidant and complement inhibitors.     

A bis(silylene)pyridine pincer ligand can stabilize mononuclear manganese(0) complexes: facile access to isolable analogues of the elusive d7-Mn(CO)5 radical

Using the potentially tridentate N,N′-bis(N-heterocyclic silylene)pyridine [SiNSi] pincer-type ligand, 2,6-N,N′-diethyl-bis[N,N′-di-tert-butyl(phenylamidinato)silylene] diaminopyridine, led to the first isolable bis(silylene)pyridine-stabilized manganese(0) complex, {κ³-[SiNSi]Mn(dmpe)} 4 (dmpe = (Me₂P)₂C₂H₄), which represents an isolobal 17 VE analogue of the elusive Mn(CO)₅ radical. The compound is accessible through the reductive dehalogenation of the corresponding dihalido (SiNSi)Mn(ii) complexes 1 (Cl) and 2 (Br) with potassium graphite. Exposing 4 towards the stronger π-acceptor ligands CO and 2,6-dimethylphenyl isocyanide afforded the related Mn(0) complexes κ²-[SiNSi]Mn(CO)₃ (5) and κ³-[SiNSi]Mn(CNXylyl)₂(κ¹-dmpe) (6), respectively. Remarkably, the stabilization of Mn(0) in the coordination sphere of the [SiNSi] ligand favors the d⁷ low-spin electronic configuration, as suggested by EPR spectroscopy, SQUID measurements and DFT calculations. The suitability of 4 acting as a superior pre-catalyst in regioselective hydroboration of quinolines has also been demonstrated.

An isolable bis(silylene)pyridine stabilized manganese(0) complex {κ³-[SiNSi]Mn(dmpe)}, isolobal to elusive Mn(CO)₅ radical has been synthesized and fully characterised.     

Photoredox catalysis via consecutive 2LMCT- and 3MLCT-excitation of an Fe(iii/ii)–N-heterocyclic carbene complex

Fe–N-heterocyclic carbene (NHC) complexes attract increasing attention as photosensitisers and photoredox catalysts. Such applications generally rely on sufficiently long excited state lifetimes and efficient bimolecular quenching, which leads to there being few examples of successful usage of Fe–NHC complexes to date. Here, we have employed [Fe(iii)(btz)₃]³⁺ (btz = (3,3′-dimethyl-1,1′-bis(p-tolyl)-4,4′-bis(1,2,3-triazol-5-ylidene))) in the addition of alkyl halides to alkenes and alkynes via visible light-mediated atom transfer radical addition (ATRA). Unlike other Fe–NHC complexes, [Fe(iii/ii)(btz)₃]^3+/2+ benefits from sizable charge transfer excited state lifetimes ≥0.1 ns in both oxidation states, and the Fe(iii) ²LMCT and Fe(ii) ³MLCT states are strong oxidants and reductants, respectively. The combined reactivity of both excited states enables efficient one-electron reduction of the alkyl halide substrate under green light irradiation. The two-photon mechanism proceeds via reductive quenching of the Fe(iii) ²LMCT state by a sacrificial electron donor and subsequent excitation of the Fe(ii) product to its highly reducing ³MLCT state. This route is shown to be more efficient than the alternative, where oxidative quenching of the less reducing Fe(iii) ²LMCT state by the alkyl halide drives the reaction, in the absence of a sacrificial electron donor.

An iron complex with N-heterocyclic carbene ligands engages in efficient photoredox catalysis via excited state electron transfer reactions of its Fe(ii) and Fe(iii) oxidation states.     

Structure Elucidation of Triterpenoid Saponins Found in an Immunoadjuvant Preparation of Quillaja brasiliensis Using Mass Spectrometry and 1H and 13C NMR Spectroscopy

An immunoadjuvant preparation (named Fraction B) was obtained from the aqueous extract of Quillaja brasiliensis leaves, and further fractionated by consecutive separations with silica flash MPLC and reverse phase HPLC. Two compounds were isolated, and their structures elucidated using a combination of NMR spectroscopy and mass spectrometry. One of these compounds is a previously undescribed triterpene saponin (Qb1), which is an isomer of QS-21, the unique adjuvant saponin employed in human vaccines. The other compound is a triterpene saponin previously isolated from Quillaja saponaria bark, known as S13. The structure of Qb1 consists of a quillaic acid residue substituted with a β-d-Galp-(1→2)-[β-d-Xylp-(1→3)]-β-d-GlcpA trisaccharide at C3, and a β-d-Xylp-(1→4)-α-l-Rhap-(1→2)-[α-l-Arap-(1→3)]-β-d-Fucp moiety at C28. The oligosaccharide at C28 was further substituted at O4 of the fucosyl residue with an acyl group capped with a β-d-Xylp residue.     

Solid-state 17O NMR study of α-d-glucose: exploring new frontiers in isotopic labeling,sensitivity enhancement,and NMR crystallography

We report synthesis and solid-state ¹⁷O NMR characterization of α-d-glucose for which all six oxygen atoms are site-specifically ¹⁷O-labeled. Solid-state ¹⁷O NMR spectra were recorded for α-d-glucose/NaCl/H₂O (2/1/1) cocrystals under static and magic-angle-spinning (MAS) conditions at five moderate, high, and ultrahigh magnetic fields: 14.1, 16.4, 18.8, 21.1, and 35.2 T. Complete ¹⁷O chemical shift (CS) and quadrupolar coupling (QC) tensors were determined for each of the six oxygen-containing functional groups in α-d-glucose. Paramagnetic Cu(ii) doping was found to significantly shorten the spin–lattice relaxation times for both ¹H and ¹⁷O nuclei in these compounds. A combination of the paramagnetic Cu(ii) doping, new CPMAS CryoProbe technology, and apodization weighted sampling led to a sensitivity boost for solid-state ¹⁷O NMR by a factor of 6–8, which made it possible to acquire high-quality 2D ¹⁷O multiple-quantum (MQ) MAS spectra for carbohydrate compounds. The unprecedented spectral resolution offered by 2D ¹⁷O MQMAS spectra permitted detection of a key structural difference for a single hydrogen bond between two types of crystallographically distinct α-d-glucose molecules. This work represents the first case where all oxygen-containing functional groups in a carbohydrate molecule are site-specifically ¹⁷O-labeled and fully characterized by solid-state ¹⁷O NMR. Gauge Including Projector Augmented Waves (GIPAW) DFT calculations were performed to aid ¹⁷O and ¹³C NMR signal assignments for a complex crystal structure where there are six crystallographically distinct α-d-glucose molecules in the asymmetric unit.

We report the first “total synthesis” of ¹⁷O-labeled d-glucose and its solid-state ¹⁷O NMR characterization with unprecedented sensitivity and resolution.     

Between imide,imidyl and nitrene – an imido iron complex in two oxidation states

Imidyl and nitrene metal species play an important role in the N-functionalisation of unreactive C–H bonds as well as the aziridination of olefines. We report on the synthesis of the trigonal imido iron complexes [Fe(NMes)L₂]^0,− (L = –N{Dipp}SiMe₃); Dipp = 2,6-diisopropyl-phenyl; Mes = (2,4,6-trimethylphenyl) via reaction of mesityl azide (MesN₃) with the linear iron precursors [FeL₂]^0,−. UV-vis-, EPR-, ⁵⁷Fe Mössbauer spectroscopy, magnetometry, and computational methods suggest for the reduced form an electronic structure as a ferromagnetically coupled iron(ii) imidyl radical, whereas oxidation leads to mixed iron(iii) imidyl and electrophilic iron(ii) nitrene character. Reactivity studies show that both complexes are capable of H atom abstraction from C–H bonds. Further, the reduced form [Fe(NMes)L₂]⁻ reacts nucleophilically with CS₂ by inserting into the imido iron bond, as well as electrophilically with CO under nitrene transfer. The neutral [Fe(NMes)L₂] complex shows enhanced electrophilic behavior as evidenced by nitrene transfer to a phosphine, yet in combination with an overall reduced reactivity.

A pair of trigonal imido iron complexes ([Fe(NMes)L₂]^0,−) in two oxidation states is reported. The anionic complex K{crypt.222}[Fe(NMes)L₂] is best described as an iron(ii) imide.     

Chelation-assisted C–C bond activation of biphenylene by gold(i) halides

A chelation-assisted oxidative addition of gold(i) into the C–C bond of biphenylene is reported here. The presence of a coordinating group (pyridine, phosphine) in the biphenylene unit enabled the use of readily available gold(i) halide precursors providing a new, straightforward entry towards cyclometalated (N^C^C)- and (P^C)-gold(iii) complexes. Our study, combining spectroscopic and crystallographic data with DFT calculations, showcases the importance of neighboring, weakly coordinating groups towards the successful activation of strained C–C bonds by gold.

Pyridine and phosphine directing groups promote the C–C activation of biphenylene by readily available gold(i) halides rendering a new entry to (N^C^C)- and (P^C)-gold(iii) species.

Activation of C–C bonds by transition metals is challenging given their inertness and ubiquitous presence alongside competing C–H bonds.¹ Both the intrinsic steric hindrance as well as the highly directional character of the p orbitals involved in the σ_C–C bond impose a high kinetic barrier for this type of processes.^2,3 Biphenylene, a stable antiaromatic system featuring two benzene rings connected via a four-membered cycle, has found widespread application in the study of C–C bond activation. Since the seminal report from Eisch et al. on the oxidative addition of a nickel(0) complex into the C–C bond of biphenylene,⁴ several other late transition metals have been successfully applied in this context.⁵ Interestingly, despite the general reluctance of gold(i) to undergo oxidative addition,⁶ its oxidative insertion into the C–C bond of biphenylene was demonstrated in two consecutive reports by the groups of Toste^7a and Bourissou,^7b respectively. The high energy barrier associated with the oxidation of gold could be overcome by the utilization of gold(i) precursors bearing ligands that exhibit either a strongly electron-donating character (e.g. IPr = [1,3-bis(2,6-diisopropylphenyl)imidazole-2-ylidene])^7a or small bite angles (e.g. DPCb = diphosphino-carborane).^7b,8 In line with these two approaches, more sophisticated bidentate (N^C)- and (P^N)-ligated gold(i) complexes have also been shown to aid the activation of biphenylene at ambient temperature (Scheme 1a).^7c,dOpen in a separate windowScheme 1(a) Previous reports on oxidative addition of ligated gold(i) precursors onto biphenylene. (b) This work: pyridine- and phosphine-directed C–C bond activation of biphenylene by commercially available gold(i) halides.In this context, we hypothesized that the oxidative insertion of gold(i) into the C–C bond of biphenylene could be facilitated by the presence of a neighboring chelating group.⁹ This approach would not only circumvent the need for gold(i) precursors featuring strong σ-donor or highly tailored bidentate ligands but also offer a de novo entry towards interesting, less explored ligand templates. However, recent work by Breher and co-workers showcased the difficulty of achieving such a transformation.¹⁰Herein, we report the oxidative insertion of readily available gold(i) halide precursors into the C–C bond of biphenylene. The appendage of both pyridine and phosphine donors in close proximity to the σ_C–C bond bridging the two aromatic rings provides additional stabilization to the metal center and results in a de novo entry to cyclometalated (N^C^C)- and (P^C)gold(iii) complexes (Scheme 1b).Our study commenced with the preparation of 5-chloro-1-pyridino-biphenylene system 2via Pd-catalyzed Suzuki cross coupling reaction between 2-bromo-3-methylpyridine and 2-(5-chlorobiphenylen-1-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane 1 (Scheme 2).¹¹ To our delight, the reaction of 2 with gold(i) iodide in toluene at 130 °C furnished complex κ³-(N^C^C)Au(iii)–I 3 in 60% yield.^12,13 Complex 3 was isolated as yellow plate-type crystals from the reaction mixture and its molecular structure was unambiguously assigned by NMR spectroscopy, high-resolution mass spectrometry (HR-MS) and crystallographic analysis. Complex 3 exhibits the expected square-planar geometry around the metal center, with a Au–I bond length of 2.6558(3) Å.¹⁴ The choice of a neutral weakly bound gold(i)-iodide precursor is key for a successful reaction outcome: similar reactions in the presence of [(NHC)AuCl + AgSbF₆] failed to deliver the desired biscyclometalation adducts, as reported by Breher et al. in ref. 10. The oxidative insertion of gold(i) iodide into the four-membered ring of pyridino-substituted biphenylene provides a novel and synthetically efficient entry to κ³-(N^C^C)gold(iii) halides. These species have recently found widespread application as precursors for the characterization of highly labile, catalytically relevant gold(iii) intermediates,^15a–d as well as for the preparation of highly efficient emitters in OLEDs.^15e–g Previous synthetic routes towards these attractive biscyclometalated gold(iii) systems involved microwave-assisted double C–H functionalization reactions that typically proceed with low to moderate yields.^15aOpen in a separate windowScheme 2Synthesis of complex 3via oxidative addition of Au(i) into the C–C bond of pyridine-substituted biphenylene. X-ray structures of complex 3 with atoms drawn using 50% probability ellipsoids. Hydrogen atoms have been omitted for clarity. Additional selected bond distances [Å]: N–Au = 2.126(2), C1–Au = 1.973(2), C2–Au = 2.025(2), Au–I = 2.6558(3) and bond angles [deg]: N–Au–I = 99.25(6), N–Au–C1 = 79.82(9), C1–Au–C2 = 81.2(1), C2–Au–I = 99.73(8). For experimental details, see ESI.^†Encouraged by the successful results obtained with the pyridine-substituted biphenylene and considering the prominent use of phosphines in gold chemistry,^6,16 we wondered whether the same reactivity would be observed for a P-containing system. To this end, both adamantyl- and tert-butyl-substituted phosphines were appended in C1 position of the biphenylene motif. Starting from 5-chlorobiphenylene-1-carbaldehyde 4, phosphine-substituted biphenylenes 5a and 5b could be accessed in 3 steps (aldehyde reduction to the corresponding alcohol, Appel reaction and nucleophilic displacement of the corresponding benzylic halide) in 64 and 57% overall yields, respectively.¹³ The reactions of 5a and 5b with commercially available gold(i) halides (Me₂SAuCl and AuI) furnished the corresponding mononuclear complexes 7a–b and 8a–b, respectively (Scheme 3).¹³ All these complexes were fully characterized and the structures of 7a, 7b and 8a were unambiguously characterized by X-ray diffraction analysis.¹³ Interestingly, the nature of the halide has a clear effect on the chemical shift of the phosphine ligand so that a Δδ of ca. 5 ppm can be observed in the ³¹P NMR spectra of 7a–b (Au–Cl) compared to 8a–b (Au–I), the latter being the more deshielded. The Au–X bond length is also impacted, with a longer Au–I distance (2.5608(1) Å for 8a) compared to that measured in the Au–Cl analogue (2.2941(7) Å for 7a) (Δd = 0.27 Å).¹³Open in a separate windowScheme 3Synthesis and reactivity of complexes 7a–b, 8a–b, 9 and 10. X-ray structure of complexes 11b, 12 and 14 with atoms drawn using 50% probability ellipsoids. Hydrogen atoms have been omitted for clarity. For experimental details and X-ray structures see ESI.^†Despite numerous attempts to promote the C–C activation in these complexes,^10,13 all reactions resulted in the formation of highly stable cationic species 11a–b and 12, which could be easily isolated from the reaction media. In the case of cationic mononuclear-gold(i) complexes 11, a ligand scrambling reaction in which the chloride ligand is replaced by a phosphine in the absence of a scavenger, a process previously described for gold(i) species, can be used to justify the reaction outcome.¹⁷ The formation of dinuclear gold complex 12 can be ascribed to the combination of a strong aurophilic interaction between the two gold centers (Au–Au = 2.8874(4) Å) and the stabilizing η²-coordination of the metal center to the aromatic ring of biphenylene. Similar η²-coordinated gold(i) complexes have been reported but, to the best of our knowledge, only as mononuclear species.¹⁸Taking into consideration the observed geometry of complexes 7a–b in the solid state,¹³ the facile formation of stable cationic species 11 and 12 and the lack of reactivity of the gold(i) iodides 8a–b, we hypothesized that the free rotation around the C–P bond was probably restricted, placing the gold(i) center away from the biphenylene system and thus preventing the desired oxidative insertion reaction. To overcome this problem, we set out to elongate the arm bearing the phosphine unit with an additional methylene group, introduced via a Wittig reaction from compound 4 to yield ligand 6, prepared in 4 steps in 27% overall yield. Coordination with Me₂SAuCl and AuI resulted in gold(i) complexes 9 and 10, respectively (Scheme 3). The structure of 9 was unambiguously assigned by X-ray diffraction analysis and a similar environment around the metal center to that determined for complex 7a was observed for this complex.¹³With complexes 9 and 10 in hand, we explored their reactivity towards C–C activation of the four-membered ring of biphenylene.¹⁹ After chloride abstraction and upon heating at 100 °C for 5 hours, ring opening of the biphenylene system was observed for complex 9. Interestingly, formation of mono-cyclometalated adduct 13 was exclusively observed (the structure of 13 was confirmed by ¹H, ¹³C, ³¹P, ¹⁹F, ¹¹B and 2D NMR spectroscopy and HR-MS).¹³ The solvent appears to play a major role in this process, as performing the reaction in non-chlorinated solvents resulted in stable cationic complexes similar to 11.^13,20,21 The presence of adventitious water is likely responsible for the formation of the monocyclometalated (P^C)gold(iii) complex 13 as when the reaction was carried out in C₂H₄Cl₂ previously treated with D₂O, the corresponding deuterated adduct 13-d could be detected in the reaction media. These results showcase the difficulties associated with the biscyclometalation for P-based complexes as well as the labile nature of the expected biscyclometalated adducts. Interestingly though, these processes can be seen as a de novo entry towards relatively underexplored (P^C)gold(iii) species.²²The C–C activation was further confirmed by X-ray diffraction analysis of the phosphonium salt 14, which arise from the reductive elimination at the gold(iii) center in 13 upon exchange of the BF₄⁻ counter-anion with the weakly coordinating sodium tetrakis[3,5-bis(trifluoromethyl)phenyl]borate (NaBAr^F).^13,23 The phosphorus atom is four-coordinate, with weak bonding observed to the distant counter-anion and a distorted tetrahedral geometry (C1–P–C2 = 95.05(17), C2–P–C3 = 112.1(1), C3–P–C4 = 116.6(1), C4–P–C1 = 107.4(2) deg). These results represent the third example in which the C(sp²)–P bond reductive elimination at gold(iii) has been reported.²⁴Further, it is important to note that, in contrast to the reactivity observed for the pyridine-substituted biphenylene, neither P-coordinated gold(i) iodo complexes 8a, 8b nor 10 reacted to give cyclometalated products despite prolonged heating, which highlights the need for highly reactive cationized gold(i) species to undergo oxidative addition when phosphine ligands are flanking the C–C bond.¹³To get a deeper understanding on the observed differences in reactivity for the N- vs. P-based directing groups, ground- and transition-state structures for the oxidative insertion of gold(i) halides in C1-substituted biphenylenes were computed by DFT calculations. The reactions of Py-substituted 2 with AuI to give 3 (I) and those of P-substituted 7a (II) and 9 (III) featuring the cationization of the gold(i) species were chosen as models for comparative purposes with the experimental conditions (Fig. 1 and S1–S10 in the ESI^†).^25–27 The computed activation energies for the three processes are in good agreement with the experimental data. The pyridine-substituted biphenylene I exhibits the lowest activation barrier for the oxidative insertion process (ΔG^‡ = 34.4 kcal mol⁻¹). The reaction on the phosphine-substituted derivatives II and III proved to be, after cationization of the corresponding gold(i) halide complexes (II-BF₄, III-BF₄) higher in energy (ΔG^‡ = 39.6 and 46.3 kcal mol⁻¹ respectively), although the obtained values do not rule out the feasibility of the C–C activation process. The transition state between I and I′ exhibits several interesting geometrical features: (a) the biphenylene is significantly bent, (b) the cleavage of the C–C bond is well advanced (d_C–C = 1.898 Å in TSIvs. d_C–C = 1.504 Å in I), and (c) the two C and the I atoms form a Y-shape around gold with minimal coordination from the pyridine (d_N–Au = 2.742 Å in TSIvs. d_N–Au = 2.093 Å in I and 2.157 Å in I′, respectively). The transition-state structures found for the P-based ligands (TSII and TSIII) also show an elongation of the C–C bond and display a bent biphenylene. However, much shorter P–Au distances (d_P–Au = 2.330 Å for TSII and 2.314 Å for TSIII) can be observed compared to the pyridine-based system, as expected due to the steric and electronic differences between these two coordinating groups. Analogously, longer C–Au distances were also found for the P-based systems (d_C1–Au = 2.152 Å for TSIvs. 2.235 Å and 2.204 Å for TSII and TSIII; d_C2–Au = 2.143 Å for TSIvs. 2.219 Å and 2.162 Å for TSII and TSIII), with a larger deviation of square planarity for Au in TSIII compared to TSII.^28,29 These results suggest that, provided the appropriate distance to the C–C bond is in place, the strong coordination of phosphorous to the gold(i) center does not prevent the C–C activation of biphenylene but other reactions (i.e. formation of diphosphine gold(i) cationic species, protodemetalation) can outcompete the expected biscyclometalation process. In contrast, a weaker donor such as pyridine offers a suitable balance bringing the gold in close proximity to the C–C bond and enables both the oxidative cleavage as well as the formation of the double metalation product.Open in a separate windowFig. 1Energy profile (ΔG and ΔG^‡ in kcal mol⁻¹), optimized structures, transition states computed at the IEFPCM (toluene/1,2-dichloroethane)-B3PW91/DEF2QZVPP(Au,I)/6-31++G(d,p)(other atoms) level of theory for the C–C activation of biphenylene with gold(i) iodide from I and gold(i) cationic from II and III. Computed structures of the transition states (TSI, TSII and TSIII) and table summarizing relevant distances.     

Lanthanide-mediated tuning of electronic and magnetic properties in heterotrimetallic cyclooctatetraenyl multidecker self-assemblies

The synthesis of a novel family of homoleptic COT-based heterotrimetallic self-assemblies bearing the formula [LnKCa(COT)₃(THF)₃] (Ln(iii) = Gd, Tb, Dy, Ho, Er, Tm, and Yb) is reported followed by their X-ray crystallographic and magnetic characterization. All crystals conform to the monoclinic P2₁/c space group with a slight compression of the unit cell from 3396.4(2) ų to 3373.2(4) ų along the series. All complexes exhibit a triple-decker structure having the Ln(iii) and K(i) ions sandwiched by three COT²⁻ ligands with an end-bound {Ca²⁺(THF)₃} moiety to form a non-linear (153.5°) arrangement of three different metals. The COT²⁻ ligands act in a η⁸-mode with respect to all metal centers. A detailed structural comparison of this unique set of heterotrimetallic complexes has revealed consistent trends along the series. From Gd to Yb, the Ln to ring-centroid distance decreases from 1.961(3) Å to 1.827(2) Å. In contrast, the separation of K(i) and Ca(ii) ions from the COT-centroid (2.443(3) and 1.914(3) Å, respectively) is not affected by the change of Ln(iii) ions. The magnetic property investigation of the [LnKCa(COT)₃(THF)₃] series (Ln(iii) = Gd, Tb, Dy, Ho, Er, and Tm) reveals that the Dy, Er, and Tm complexes display slow relaxation of their magnetization, in other words, single-molecule magnet (SMM) properties. This behaviour is dominated by thermally activated (Orbach-like) and quantum tunneling processes for [DyKCa(COT)₃(THF)₃] in contrast to [ErKCa(COT)₃(THF)₃], in which the thermally activated and Raman processes appear to be relevant. Details of the electronic structures and magnetic properties of these complexes are further clarified with the help of DFT and ab initio theoretical calculations.

A new class of heterotrimetallic COT-based self-assemblies accommodates metals from groups I–III in three different oxidation states and enables tuning of electronic and magnetic properties.     

Stoichiometric to catalytic reactivity of the aryl cycloaurated species with arylboronic acids: insight into the mechanism of gold-catalyzed oxidative C(sp2)–H arylation

Based on the well-defined five-membered aryl gold(iii) complexes, [Au(tpy)X₂] (3a and 3b) and [AuBr(Ph)(tpy)] (7), as well as the aryl gold(iii) complex [AuCl₂(Ph)(tpy)] (8) (tpy = 2-(o-tolyl)pyridine) as reliable models, we present a detailed study of the mechanism for gold(iii)-catalyzed oxidative cross-coupling reactions between cycloaurable arenes and arylboronic acids. Here we report the direct evidence for a mechanistic proposal including arene C–H activation, transmetallation and biaryl reductive elimination. The chelation-assisted C–H activation strategy has been used for the development of the gold(iii)-catalyzed C–H bond arylation of arenes with aryl reagents to forge extended π-conjugated systems.     

The mechanism of Fe induced bond stability of uranyl(v)

The stabilization of uranyl(v) (UO₂¹⁺) by Fe(ii) in natural systems remains an open question in uranium chemistry. Stabilization of U^VO₂¹⁺ by Fe(ii) against disproportionation was also demonstrated in molecular complexes. However, the relation between the Fe(ii) induced stability and the change of the bonding properties have not been elucidated up to date. We demonstrate that U(v) – oaxial bond covalency decreases upon binding to Fe(ii) inducing redirection of electron density from the U(v) – oaxial bond towards the U(v) – equatorial bonds thereby increasing bond covalency. Our results indicate that such increased covalent interaction of U(v) with the equatorial ligands resulting from iron binding lead to higher stability of uranyl(v). For the first time a combination of U M_4,5 high energy resolution X-ray absorption near edge structure (HR-XANES) and valence band resonant inelastic X-ray scattering (VB-RIXS) and ab initio multireference CASSCF and DFT based computations were applied to establish the electronic structure of iron-bound uranyl(v).

The role of Fe in the increased stability of uranyl(v) is clarified by using state of the art uranium metalorganic chemistry, advanced X-ray spectroscopic approaches and computations.     

Adaptive coordination assemblies based on a flexible tetraazacyclododecane ligand for promoting carbon dioxide fixation

Coordination hosts based on flexible ligands have received increasing attention due to their inherent adaptive cavities that often show induced-fit guest binding and catalysis like enzymes. Herein, we report the controlled self-assembly of a series of homo/heterometallic coordination hosts (Me₄enPd)_2n(ML)_n [n = 2/3; M = Zn(ii)/Co(ii)/Ni(ii)/Cu(ii)/Pd(ii)/Ag(i); Me₄en: N,N,N′,N′-tetramethylethylenediamine] with different shapes (tube/cage) from a flexible tetraazacyclododecane-based pyridinyl ligand (L) and cis-blocking Me₄enPd(ii) units. While the Ag(i)-metalated ligand (AgL) gave rise to the formation of a (Me₄enPd)₄(ML)₂-type cage, all other M(ii) ions led to isostructural (Me₄enPd)₆(ML)₃-type tubular complexes. Structural transformations between cages and tubes could be realized through transmetalation of the ligand. The buffering effect on the ML panels endows the coordination tubes with remarkable acid–base resistance, which makes the (Me₄enPd)₆(ZnL)₃ host an effective catalyst for the CO₂ to CO₃²⁻ conversion. Control experiments suggested that the integration of multiple active Zn(ii) sites on the tubular host and the perfect geometry match between CO₃²⁻ and the cavity synergistically promoted such a conversion. Our results provide an important strategy for the design of adaptive coordination hosts to achieve efficient carbon fixation.

A series of coordination hosts were prepared and their applications in CO₂ fixation were studied.     

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.     

C(sp3)–H oxygenation via alkoxypalladium(ii) species: an update for the mechanism

Pd-catalyzed C(sp³)–H oxygenation has emerged as an attractive strategy for organic synthesis. The most commonly proposed mechanism involves C(sp³)–H activation followed by oxidative addition of an oxygen electrophile to give an alkylpalladium(iv) species and further C(sp³)–O reductive elimination. In the present study of γ-C(sp³)–H acyloxylation of amine derivatives, we show a different mechanism when tert-butyl hydroperoxide (TBHP) is used as an oxidant—namely, a bimetallic oxidative addition-oxo-insertion process. This catalytic model results in an alkoxypalladium(ii) intermediate from which acyloxylation and alkoxylation products are formed. Experimental and computational studies, including isolation of the putative post-oxo-insertion alkoxypalladium(ii) intermediates, support this mechanistic model. Density functional theory reveals that the classical alkylpalladium(iv) oxidative addition pathway is higher in energy than the bimetallic oxo-insertion pathway. Further kinetic studies revealed second-order dependence on [Pd] and first-order on [TBHP], which is consistent with DFT analysis. This procedure is compatible with a wide range of acids and alcohols for γ-C(sp³)–H oxygenation. Preliminary functional group transformations of the products underscore the great potential of this protocol for structural manipulation.

Alkoxypalladium(ii) species lead to γ-C(sp³)–H acyloxylation and alkoxylation products using tert-butyl hydroperoxide as the oxidant.     

Pt(ii)-coordinated tricomponent self-assemblies of tetrapyridyl porphyrin and dicarboxylate ligands: are they 3D prisms or 2D bow-ties?

Thermodynamically favored simultaneous coordination of Pt(ii) corners with aza- and carboxylate ligands yields tricomponent coordination complexes with sophisticated structures and functions, which require careful structural characterization to paint accurate depiction of their structure–function relationships. Previous reports claimed that heteroleptic coordination of cis-(Et₃P)₂Pt^II with tetrapyridyl porphyrins (M′TPP, M′ = Zn or H₂) and dicarboxylate ligands (XDC) yielded 3D tetragonal prisms containing two horizontal M′TPP faces and four vertical XDC pillars connected by eight Pt(ii) corners, even though such structures were not supported by their ¹H NMR data. Through extensive X-ray crystallographic and NMR studies, herein, we demonstrate that self-assembly of cis-(Et₃P)₂Pt^II, M′TPP, and four different XDC linkers having varied lengths and rigidities actually yields bow-tie (⋈)-shaped 2D [{cis-(Et₃P)₂Pt}₄(M′TPP) (XDC)₂]⁴⁺ complexes featuring a M′TPP core and two parallel XDC linkers connected by four heteroleptic Pt^II corners instead of 3D prisms. This happened because (i) irrespective of their length (∼7–11 Å) and rigidity, the XDC linkers intramolecularly bridged two adjacent pyridyl-N atoms of a M′TPP core via Pt^II corners instead of connecting two cofacial M′TPP ligands and (ii) bow-tie complexes are entropically favored over prisms. The electron-rich ZnTPP core of a representative bow-tie complex selectively formed a charge-transfer complex with highly π-acidic 1,4,5,8,9,12-hexaazatriphenylene-2,3,6,7,10,11-heaxacarbonitrile but not with a π-donor such as pyrene. Thus, this work not only produced novel M′TPP-based bow-tie complexes and demonstrated their selective π-acid recognition capability, but also underscored the importance of proper structural characterization of supramolecular assemblies to ensure accurate depiction of their structure–property relationships.

Thermodynamically favored heteroleptic coordination of Pt(ii) corners with tetrapyridyl porphyrins and dicarboxylate ligands produces 2D bow-tie shaped complexes instead of previously mischaracterized 3D tetragonal prisms.     

Targeting antioxidant pathways with ferrocenylated N-heterocyclic carbene supported gold(i) complexes in A549 lung cancer cells

Ferrocene containing N-heterocyclic carbene (NHC) ligated gold(i) complexes of the type [Au(NHC)₂]⁺ were prepared and found to be capable of regulating the formation of reactive oxygen species (ROS) via multiple mechanisms. Single crystal X-ray analysis of bis(1-(ferrocenylmethyl)-3-mesitylimidazol-2-ylidene)-gold(i) chloride (5) and bis(1,3-di(ferrocenylmethyl)imidazol-2-ylidene)-gold(i) chloride (6) revealed a quasi-linear geometry around the gold(i) centers (i.e., the C–Au–C bond angle were measured to be ∼177° and all the Au–C_carbene bonds distances were in the range of 2.00 (7)–2.03 (1) Å). A series of cell studies indicated that cell proliferation inhibition and ROS generation were directly proportional to the amount of ferrocene contained within the [Au(NHC)₂]⁺ complexes (IC₅₀ of 6 < 5 < bis(1-benzyl-3-mesitylimidazol-2-ylidene)-gold(i) chloride (4)). Complexes 4–6 were also confirmed to inhibit thioredoxin reductase as inferred from lipoate reduction assays and increased chelatable intracellular zinc concentrations. RNA microarray gene expression assays revealed that 6 induces endoplasmic reticulum stress response pathways as a result of ROS increase.     

Bioactive Abietane-Type Diterpenoid Glycosides from Leaves of Clerodendrum infortunatum (Lamiaceae)

In this study, two previously undescribed diterpenoids, (5R,10S,16R)-11,16,19-trihydroxy-12-O-β-d-glucopyranosyl-(1→2)-β-d-glucopyranosyl-17(15→16),18(4→3)-diabeo-3,8,11,13-abietatetraene-7-one (1) and (5R,10S,16R)-11,16-dihydroxy-12-O-β-d-glucopyranosyl-(1→2)-β-d-glucopyranosyl-17(15→16),18(4→3)-diabeo-4-carboxy-3,8,11,13-abietatetraene-7-one (2), and one known compound, the C₁₃-nor-isoprenoid glycoside byzantionoside B (3), were isolated from the leaves of Clerodendrum infortunatum L. (Lamiaceae). Structures were established based on spectroscopic and spectrometric data and by comparison with literature data. The three terpenoids, along with five phenylpropanoids: 6′-O-caffeoyl-12-glucopyranosyloxyjasmonic acid (4), jionoside C (5), jionoside D (6), brachynoside (7), and incanoside C (8), previously isolated from the same source, were tested for their in vitro antidiabetic (α-amylase and α-glucosidase), anticancer (Hs578T and MDA-MB-231), and anticholinesterase activities. In an in vitro test against carbohydrate digestion enzymes, compound 6 showed the most potent effect against mammalian α-amylase (IC₅₀ 3.4 ± 0.2 μM) compared to the reference standard acarbose (IC₅₀ 5.9 ± 0.1 μM). As yeast α-glucosidase inhibitors, compounds 1, 2, 5, and 6 displayed moderate inhibitory activities, ranging from 24.6 to 96.0 μM, compared to acarbose (IC₅₀ 665 ± 42 μM). All of the tested compounds demonstrated negligible anticholinesterase effects. In an anticancer test, compounds 3 and 5 exhibited moderate antiproliferative properties with IC₅₀ of 94.7 ± 1.3 and 85.3 ± 2.4 μM, respectively, against Hs578T cell, while the rest of the compounds did not show significant activity (IC₅₀ > 100 μM).