Bidentate Diphosphine Research Articles

Modulating the Anticancer Activity of Square‐Planar Platinum (II) Complex by Its Chelated Diphosphine

ABSTRACTThis work reports the preparations and anticancer activities of a set of platinum (II) complexes. Two types of bidentate ligands, azadiphosphine (PNP) and diphosphine (PP), were applied to afford different kinds of platinum centers, the homoleptic complexes, [Pt (PNP)2]2+ (1 and 2) and [Pt (PP)2]2+ (4), and the hybrid complex, [Pt (PNP)(PP)]2+ (3). All these complexes are characterized by various analytical techniques, and their structures were validated using single‐crystal X‐ray diffraction analysis. Notably, the stability of the complexes 1–4 is differentiated both in phosphate‐buffered saline (PBS) and in the culture media (RPMI‐1640), relative to the type of coordinated diphosphine ligands, specifically, the more PNP ligands, the less stability. The bite angles of P‐Pt‐P bonds in 1–4 would be reliant on their stability, so that complexes 1 and 2 with small bite angles tend to be labile. A mechanistic understanding on the decomposition of 2 is proposed with the aid of mass analysis. As a result, their anticancer activities should be also associated with their stability so that the chelated ligands, with more PNP ligands, lead to more cytotoxicity. Mechanistically, the poisonous platinum (II) derivatives of complex 2 should interact with the nucleus DNA, whereas the intact complex 4 is not traceable, confirming from a γ‐H2AX‐related immunofluorescence staining kit. Additionally, complex 2 exhibits severe toxicity toward several cancer cells as well as a normal cell. Furthermore, complex 2 has inhibited the formation and viability of three‐dimensional T24 mammospheres, reminding it of a promising candidate for anticancer treatments. Overall, the present work provides a way for the systematic investigation to elucidate how a bidentate diphosphine ligand modulates the stability and the anticancer activities of the corresponding square‐planner platinum (II) complex.

Ligand and Metal Effects in the Gas‐Phase Fragmentation of Thiomethoxymethyl Complexes

While the collision‐induced dissociation (CID) of the mass‐selected cation [(Ph3P)2Pt(CH2SCH3)]+ selectively liberates PPh3, the diphosphine complex [(dppe)Pt(CH2SCH3)]+ (dppe = 1,2‐bis(diphenylphosphino)ethane) ejects C2H4, CH2S, and (CH3)2S instead. The analogous palladium complexes [(Ph3P)2Pd(CH2SCH3)]+ and [(dppe)Pd(CH2SCH3)]+ show similar reactivity, except that C–H‐bond activation is completely lacking. For other bidentate diphosphine ligands such as dppm, dppv, dppp, dppb, dppbz, dppf, and xantphos, a correlation of the dominant reaction channels with the bite angle is observed. For bite angles > 90°, hydrogen‐atom transfer is favored, as evidenced by an increase in dimethyl‐sulfide loss. For smaller bite angles (< 90°), intramolecular activation of the thiomethoxymethyl ligand predominates, thus resulting in increased losses of thioformaldehyde and ethene. The results of the CID experiments are compared with those for [(bipy)Pt(CH2SCH3)]+, for which the loss of C2H4 is observed as the main process. DFT calculations for the complexes [(dppe)Pt(CH2SCH3)]+ and [(bipy)Pt(CH2SCH3)]+ together with the experimental findings uncover subtle differences in the underlying reaction mechanisms.

Palladium-catalyzed dicarbonylation of 1,3-butadiene with bidentate phosphine ligands: A density functional theory study

DFT calculations have been performed to discover the mechanism for the synthesis of dimethyl adipate (DMA) by 1,3-butadiene (BD) dicarbonylation catalyzed by a complex consisting of palladium and a bidentate diphosphine ligand. The computational results indicate that BD dicarbonylation involves two catalytic stages with the same reaction mechanism including terminal alkenyl insertion, CO migratory insertion, and methanolysis. Four different reaction routes have been explored, the pathway yielding linear DMA has the lowest alkenyl C-H insertion barrier with an overall barrier of 13.4 kcal·mol–1. The regioselectivity of the BD dicarbonylation depends mainly on the barrier of the alkenyl insertion into the palladium-hydrogen complex site. The computations well reproduced the experimentally observed linear selectivity.

High-Intensity Circular Dichroism of Head-To-Tail Regioregular Poly(1,4-Phenylene)s in the Aggregated State.

Circular dichroism (CD) studies on poly(1,4-phenylene)s bearing a chiral side chain in the aggregated conditions were carried out. Little CD was observed in a solution form, while addition of a poor solvent into the polyphenylene solution induced aggregation and a strong CD was observed, accordingly. Applying the controlled degree of polymerization (DP) of poly(1,4-phenylene) in the use of bidentate diphosphine Chiraphos as a ligand for the nickel catalyst, the relationship of DP with CD strength was studied to reveal to show the highest CD at the DP=84 (gabs=ca. 2×10-2). It was also found that the related aggregation was observed in good solvent 1,2-dichloroethane upon standing the solution at 4 °C for 3-23 days to observe gabs=ca. 10-1. Studies on the substituent effect of poly(1,4-phenylene) suggested that CD behaviors were dependent on the type of non-chiral substituent on the aromatic ring as well as the side-chain chirality.

Development of Effective Bidentate Diphosphine Ligands of Ruthenium Catalysts toward Practical Hydrogenation of Carboxylic Acids

Abstract Hydrogenation of carboxylic acids (CAs) to alcohols represents one of the most ideal reduction methods for utilizing abundant CAs as alternative carbon and energy sources. However, systematic studies on the effects of metal-to-ligand relationships on the catalytic activity of metal complex catalysts are scarce. We previously demonstrated a rational methodology for CA hydrogenation, in which CA-derived cationic metal carboxylate [(PP)M(OCOR)]+ (M = Ru and Re; P = one P coordination) served as the catalyst prototype for CA self-induced CA hydrogenation. Herein, we report systematic trial-and-error studies on how we could achieve higher catalytic activity by modifying the structure of bidentate diphosphine (PP) ligands of molecular Ru catalysts. Carbon chains connecting two P atoms as well as Ar groups substituted on the P atoms of PP ligands were intensively varied, and the induction of active Ru catalysts from precatalyst Ru(acac)3 was surveyed extensively. As a result, the activity and durability of the (PP)Ru catalyst substantially increased compared to those of other molecular Ru catalyst systems, including our original Ru catalysts. The results validate our approach for improving the catalyst performance, which would benefit further advancement of CA self-induced CA hydrogenation.

Aqueous Suzuki–Miyaura Coupling with Ultralow Palladium Loading and Simple Product Separation

The diphosphine ligand N,N-bis(diphenylphosphanylmethyl)-aniline (bdppma) and PdCl2 afforded a Suzuki–Miyaura catalyst [(bdppma­)PdCl2] that was highly efficient at an ultralow catalyst loading (0.001 mol%) in 20:1 H2O–EtOH. This low catalyst loading in an aqueous solvent system permitted simple product separation by direct filtration without the need for chromatography. The ligand bdppma imparted surprisingly better reactivity than that achieved with other bidentate diphosphine ligands, but the catalytic system had a slightly narrower substrate scope than some similar Pd catalysts reported previously.

Palladium-catalysed methoxycarbonylation of ethene with bidentate diphosphine ligands: a density functional theory study.

Catalytic methoxycarbonylation of ethene with a bidentate tertiary phosphine (DTBPX) and palladium has been explored at the B3PW91-D3/PCM level of density functional theory. Three different pathways for formation of methyl propanoate (MePro) have been studied, namely carbomethoxy (A), ketene (B) and hydride-hydroxyalkylpalladium pathways (C), the latter of which is favoured because it has the lowest overall kinetic barrier. After intermolecular methanolysis, a hydroxyalkylpalladium complex has been characterised on pathway C, which eventually leads to the low overall barrier to produce MePro. The possibility of copolymerisation leading to oligo-/polymers has also been considered. With a computed selectivity of >99% towards the formation of MePro and a reasonably low overall kinetic barrier of 23.0 kcal mol-1, pathway C appears to be the most plausible one. Consistent with experimental data, the overall barrier increases to 30.1 kcal mol-1 for a less bulky bidentate phosphine.

Probing the Diphosphine Ligand’s Impact within Heteroleptic, Visible-Light-Absorbing Cu(I) Photosensitizers for Solar Fuels Production

In an effort to further develop earth-abundant photosensitizers for use in solar fuels production, a series of heteroleptic, visible-light-absorbing Cu(I) photosensitizers (PSs) of the design [Cu(PP)(NN)]PF6 were prepared (PP = bidentate diphosphine, Xantphos = 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene, DPEphos = bis[(2-diphenylphosphino)phenyl]ether, Nixantphos = 4,6-bis(diphenylphosphino)-10H-phenoxazine; NN = bidentate diimine, biq = 2,2′-biquinoline). The Xantphos ligand was modified to impart flexibility (PP = DPEphos) and redox activity (PP = Nixantphos) to the diphosphine backbone to probe their influence on the light-absorbing properties and excited state dynamics using steady-state and time-resolved (nanosecond) spectroscopic techniques. Following visible light excitation to populate redox-active Cu(dπ) → biq(π*) metal-to-ligand charge transfer excited states (MLCT ES), intermolecular electron transfer via reductive quenching by the N,N-dimethylaniline (DMA) electron donor produces the one-...

Toward Solution Syntheses of the Tetrahedral Au20 Pyramid and Atomically Precise Gold Nanoclusters with Uncoordinated Sites.

A long-standing objective of cluster science is to discover highly stable clusters and to use them as models for catalysts and building blocks for cluster-assembled materials. The discovery of catalytic properties of gold nanoparticles (AuNPs) has stimulated wide interests in gaseous size-selected gold clusters. Ligand-protected AuNPs have also been extensively investigated to probe their size-dependent catalytic and optical properties. However, the need to remove ligands can introduce uncertainties in both the structures and sizes of ligand-protected AuNPs for catalytic applications. Ideal model catalysts should be atomically precise AuNPs with well-defined structures and uncoordinated surface sites as in situ active centers. The tetrahedral ( Td) Au20 pyramidal cluster, discovered to be highly stable in the gas phase, provided a unique opportunity for such an ideal model system. The Td-Au20 consists of four Au(111) faces with all its atoms on the surface. Bulk synthesis of Td-Au20 with appropriate ligands would allow its catalytic and optical properties to be investigated and harnessed. The different types of its surface atoms would allow site-specific chemistry to be exploited. It was hypothesized that if the four corner atoms of Td-Au20 were coordinated by ligands the cluster would still contain 16 uncoordinated surface sites as potential in situ catalytically active centers. Phosphine ligands were deemed to be suitable for the synthesis of Td-Au20 to maintain the integrity of its pyramidal structure. Triphenyl-phosphine-protected Td-Au20 was first observed in solution, and its stability was confirmed both experimentally and theoretically. To enhance the synthetic yield, bidentate diphosphine ligands [(Ph)2P(CH2) nP(Ph)2 or L n] with different chain lengths were explored. It was hypothesized that diphosphine ligands with the right chain length might preferentially coordinate to the Td-Au20. Promising evidence was initially obtained by the formation of the undecagold by the L3 ligand. When the L8 diphosphine ligand was used, a remarkable Au22 nanocluster with eight uncoordinated Au sites, Au22(L8)6, was synthesized. With a tetraphosphine-ligand (PP3), a new Au20 nanocluster, [Au20(PP3)4]Cl4, was isolated with high yield. The crystal structure of the new Au20 core did not reveal the expected pyramid but rather an intrinsically chiral gold core. The surface of the new chiral-Au20 was fully coordinated, and it was found to be highly stable chemically. The Au22(L8)6 nanocluster represents the first and only gold core with uncoordinated gold atoms, providing potentially eight in situ catalytically active sites. The Au22 nanoclusters dispersed on oxide supports were found to catalyze CO oxidation and activate H2 without ligand removal. With further understanding about the formation mechanisms of gold nanoclusters in solution, it is conceivable that Td-Au20 can be eventually synthesized, allowing its novel catalytic and optical properties to be explored. More excitingly, it is possible that a whole family of new atomically precise gold nanoclusters can be created with different phosphine ligands.

Rhodium-Catalyzed Asymmetric N-H Functionalization of Quinazolinones with Allenes and Allylic Carbonates: The First Enantioselective Formal Total Synthesis of (-)-Chaetominine.

An unprecedented asymmetric N-H functionalization of quinazolinones with allenes and allylic carbonates was successfully achieved by rhodium catalysis with the assistance of chiral bidentate diphosphine ligands. The high efficiency and practicality of this method was demonstrated by a low catalyst loading of 1 mol % as well as excellent chemo-, regio-, and enantioselectivities with broad functional group compatibility. Furthermore, this newly developed strategy was applied as key step in the first enantioselective formal total synthesis of (-)-chaetominine.

Binuclear chromium carbonyl complexes of the highly basic small bite bidentate diphosphine bis(dimethylphosphino)methane

The structure and thermochemistry of the triads of binuclear chromium carbonyl complexes [(Me2P)2CH2]Cr2(CO)n (n=10, 9, 8), [(Me2P)2CH2]2Cr2(CO)n (n=8, 7, 6) and [(Me2P)2CH2]3Cr2(CO)n (n=6, 5, 4) have been investigated using density functional theory. The lowest-energy structures of the carbonyl-richest triad members [(Me2P)2CH2]Cr2(CO)10, [(Me2P)2CH2]2Cr2(CO)8, and [(Me2P)2CH2]3Cr2(CO)6 have long Cr⋯Cr distances indicating the absence of direct chromium bonds. The lowest energy structures of the intermediate triad members [(Me2P)2CH2]2Cr2(CO)7 and [(Me2P)2CH2]3Cr2(CO)5 systems have Cr–Cr single bonds of lengths of 3.13 and 3.39Å, respectively, and intact diphosphine ligands. However, in the lowest energy [(Me2P)2CH2]Cr2(CO)9 structure, one of the terminal CO groups is converted into a four-electron donor bridging η2-μ-CO group, retaining a long non-bonding Cr⋯Cr distance of 4.80Å. The lowest energy structure of the carbonyl-poorest [(Me2P)2CH2]Cr2(CO)8, [(Me2P)2CH2]2Cr2(CO)6, and [(Me2P)2CH2]3Cr2(CO)4 members of each triad show different features. In the lowest energy [(Me2P)2CH2]Cr2(CO)8 structure the ligand splits into separate Me2P and Me2PCH2 units, both of which bridge a Cr–Cr bond of length 3.06Å. The lowest energy [(Me2P)2CH2]2Cr2(CO)6 structure has a four-electron donor bridging η2-μ-CO group and a Cr–Cr single bond of length 2.91Å. The lowest energy [(Me2P)2CH2]3Cr2(CO)4 structure is a triplet structure with a Cr–Cr single bond of length 3.03Å.

Electronic and optical properties of the Au22[1,8-bis(diphenylphosphino) octane]6 nanoclusters disclosed by DFT and TD-DFT calculations

Time-dependent density functional theory calculations have been used to investigate the electronic and optical properties of a nanocluster composed of two directly bonded Au11 subunits, held together by six bidentate diphosphine ligands: 1,8-bis(diphenylphosphino) octane. Three exchange–correlation functionals have been adopted, a general hybrid (PBE0) and two range-separated hybrids (ωB97X and CAM-B3LYP). The results obtained show that the aforementioned properties are significantly different from those of a previously studied Au11-based nanocluster formed by just one single subunit. In particular, charge transfer excitations from the inner metal core to the outer ligands affect most of the UV–visible spectrum and occur for both alkyl and aromatic ligands. This is particularly evident when thiazole molecules are bonded to the gold core: In this case Au → ligand transitions affect also the first HOMO → LUMO excitation. Moreover, the gold core of this Au22 nanocluster has eight under-coordinated Au surface atoms not engaged in bonds with the ligands. No other known organic-protected gold nanocluster has a similar feature. These gold atoms can be considered as potential in situ active sites for catalysis, their catalytic efficiency and selectivity being modulated by charge distribution.

Synthesis, characterization and DFT studies of 1, 1′-Bis(diphenylphosphino)ferrocene substituted diiron complexes: Bioinspired [FeFe] hydrogenase model complexes

The reaction of [Fe2(CO)6(μ-toluene-3, 4-benzenedithiolate)] 1 and bidentate diphosphine, 1, 1′-bis(diphenylphosphino)ferrocene (dppf) has been studied. New complexes obtained have been characterized by various spectroscopic techniques as bioinspired models of the iron hydrogenase active site. The crystal structure of [Fe2(CO)5(κ 1-dppfO)(μ-toluene-3, 4-benzenedithiolate)] 4 is reported. New iron carbonyl complexes were synthesized from the reaction of [Fe2(CO)6(μ-toluene-3, 4-benzenedithiolate)] 1 and bidentate diphosphine, 1, 1’-bis(diphenylphosphino)ferrocene (dppf). Complex 2 was catalytically active towards proton reduction in presence of acetic acid. Based on DFT calculations the HOMO and LUMO in complex 2 were found to be localized on the Fe centers of the two {Fe2S2} units.

Toward functional type III [Fe]-hydrogenase biomimics for H2 activation: insights from computation.

The chemistry of [Fe]-hydrogenase has attracted significant interest due to its ability to activate molecular hydrogen. The intriguing properties of this enzyme have prompted the synthesis of numerous small molecule mimics aimed at activating H2. Despite considerable effort, a majority of these compounds remain nonfunctional for hydrogenation reactions. By using a recently synthesized model as an entry point, seven biomimetic complexes have been examined through DFT computations to probe the influence of ligand environment on the ability of a mimic to bind and split H2. One mimic, featuring a bidentate diphosphine group incorporating an internal nitrogen base, was found to have particularly attractive energetics, prompting a study of the role played by the proton/hydride acceptor necessary to complete the catalytic cycle. Computations revealed an experimentally accessible energetic pathway involving a benzaldehyde proton/hydride acceptor and the most promising catalyst.

Dinuclear organogold(i) complexes bearing uracil moieties: chirality of Au(i)–Au(i) axis and self-assembly

Dinuclear organogold(i) complexes bearing uracil moieties were designed, wherein the chirality of the Au(i)–Au(i) axis was induced by coordination regulation of the axially chiral bidentate diphosphine ligand, and intermolecular hydrogen-bonded assemblies were formed between the uracil moieties.

ChemInform Abstract: Congested C—C Bonds by Pd‐Catalyzed Enantioselective Allyl—Allyl Cross‐Coupling, a Mechanism‐Guided Solution.

Under the influence of a chiral bidentate diphosphine ligand, the Pd-catalyzed asymmetric cross-coupling of allylboron reagents and allylic electrophiles establishes 1,5-dienes with adjacent stereocenters in high regio- and stereoselectivity. A mechanistic study of the coupling utilizing reaction calorimetry and density functional theory analysis suggests that the reaction operates through an inner-sphere 3,3′-reductive elimination pathway, which is both rate-defining and stereodefining. Coupled with optimized reaction conditions, this mechanistic detail is used to expand the scope of allyl–allyl couplings to allow the generation of 1,5-dienes with tertiary centers adjacent to quaternary centers as well as a unique set of cyclic structures.

Congested C-C bonds by Pd-catalyzed enantioselective allyl-allyl cross-coupling, a mechanism-guided solution.

Under the influence of a chiral bidentate diphosphine ligand, the Pd-catalyzed asymmetric cross-coupling of allylboron reagents and allylic electrophiles establishes 1,5-dienes with adjacent stereocenters in high regio- and stereoselectivity. A mechanistic study of the coupling utilizing reaction calorimetry and density functional theory analysis suggests that the reaction operates through an inner-sphere 3,3'-reductive elimination pathway, which is both rate-defining and stereodefining. Coupled with optimized reaction conditions, this mechanistic detail is used to expand the scope of allyl-allyl couplings to allow the generation of 1,5-dienes with tertiary centers adjacent to quaternary centers as well as a unique set of cyclic structures.

Controlling Gold Nanoclusters by Diphospine Ligands

We report the synthesis and structure determination of a new Au22 nanocluster coordinated by six bidentate diphosphine ligands: 1,8-bis(diphenylphosphino) octane (L(8) for short). Single crystal X-ray crystallography and electrospray ionization mass spectrometry show that the cluster assembly is neutral and can be formulated as Au22(L(8))6. The Au22 core consists of two Au11 units clipped together by four L(8) ligands, while the additional two ligands coordinate to each Au11 unit in a bidentate fashion. Eight gold atoms at the interface of the two Au11 units are not coordinated by any ligands. Four short gold-gold distances (2.64-2.65 Å) are observed at the interface of the two Au11 clusters as a result of the clamping force of the four clipping ligands and strong electronic interactions. The eight uncoordinated surface gold atoms in the Au22(L(8))6 nanocluster are unprecedented in atom-precise gold nanoparticles and can be considered as potential in situ active sites for catalysis.

High Catalytic Rates for Hydrogen Production Using Nickel Electrocatalysts with Seven-Membered Cyclic Diphosphine Ligands Containing One Pendant Amine

A series of Ni-based electrocatalysts, [Ni(7P(Ph)2N(C6H4X))2](BF4)2, featuring seven-membered cyclic diphosphine ligands incorporating a single amine base, 1-para-X-phenyl-3,6-triphenyl-1-aza-3,6-diphosphacycloheptane (7P(Ph)2N(C6H4X), where X = OMe, Me, Br, Cl, or CF3), have been synthesized and characterized. X-ray diffraction studies have established that the [Ni(7P(Ph)2N(C6H4X))2](2+) complexes have a square planar geometry, with bonds to four phosphorus atoms of the two bidentate diphosphine ligands. Each of the complexes is an efficient electrocatalyst for hydrogen production at the potential of the Ni(II/I) couple, with turnover frequencies ranging from 2400 to 27,000 s(-1) with [(DMF)H](+) in acetonitrile. Addition of water (up to 1.0 M) accelerates the catalysis, giving turnover frequencies ranging from 4100 to 96,000 s(-1). Computational studies carried out on the [Ni(7P(Ph)2N(C6H4X))2](2+) family indicate the catalytic rates reach a maximum when the electron-donating character of X results in the pKa of the Ni(I) protonated pendant amine matching that of the acid used for proton delivery. Additionally, the fast catalytic rates for hydrogen production by the [Ni(7P(Ph)2N(C6H4X))2](2+) family relative to the analogous [Ni(P(Ph)2N(C6H4X)2)2](2+) family are attributed to preferred formation of endo protonated isomers with respect to the metal center in the former, which is essential to attain suitable proximity to the reduced metal center to generate H2. The results of this work highlight the importance of precise pKa matching with the acid for proton delivery to obtain optimal rates of catalysis.

Avoiding MAO: Alternative Activation Methods in Selective Ethylene Oligomerization

An ionic chromium(III) species, [CrCl2(THF)4][Al(OC4F9)4] (2), has been synthesized and is shown to react with a variety of bidentate diphosphine ligands to yield complexes of the type [CrCl2(diphosphine)2][Al(OC4F9)4]. When compound 2 is combined with diphosphines Ar2PN(Me)PAr2 (Ar = 2-MeO-C6H4) and Ph2PN(i-Pr)PPh2, after activation with small amounts of AlMe3, active species for the selective oligomerization of ethylene with catalyst productivities of up to 25010 g gCr–1 h–1 are observed. Selectivity to 1-hexene or 1-octene is a function of ligand structure in an identical fashion to the MAO-activated system. A novel Cr(II) species, [Cr(Ar2PN(Me)PAr2)2][Al(OC4F9)4]2 (5), was isolated from the catalytic mixture. Compound 5 alone does not oligomerize ethylene, but reaction with MAO yields a highly active catalyst for selective ethylene oligomerization.