Dialkylbiaryl phosphines are a valuable class of ligand for Pd-catalyzed amination reactions and have been applied in a range of contexts. This perspective attempts to aid the reader in the selection of the best choice of reaction conditions and ligand of this class for the most commonly encountered and practically important substrate combinations.

Dialkylbiaryl phosphines in Pd-catalyzed amination: a user's guide

While medicinal inorganic chemistry has been practised for over 5000 years, it was not until the late 1800s when Alfred Werner published his ground-breaking research on coordination chemistry that we began to truly understand the nature of the coordination bond and the structures and stereochemistries of metal complexes. We can now readily manipulate and fine-tune their properties. This had led to a multitude of complexes with wide-ranging biomedical applications. This review will focus on the use and potential of metal complexes as important therapeutic agents for the treatment of cancer. With major advances in technologies and a deeper understanding of the human genome, we are now in a strong position to more fully understand carcinogenesis at a molecular level. We can now also rationally design and develop drug molecules that can either selectively enhance or disrupt key biological processes and, in doing so, optimize their therapeutic potential. This has heralded a new era in drug design in which we a...

Toward Multi-Targeted Platinum and Ruthenium Drugs-A New Paradigm in Cancer Drug Treatment Regimens?

https://pubs.acs.org/doi/pdf/10.1021/acs.organomet.5b00868

Impact of the Halogen Substitution Pattern on the Biological Activity of Organoruthenium 8-Hydroxyquinoline Anticancer Agents

Non-platinum complexes containing releasable biologically active ligands

Compounds that combine metal-based drugs with covalently linked targeted organic agents have been shown, in some instances, to exhibit superior anticancer properties compared to the individual counterparts. Within this framework, we prepared a series of organometallic ruthenium(II)- and osmium(II)-p-cymene complexes modified with the nonsteroidal anti-inflammatory drugs (NSAIDs) indomethacin and diclofenac. The NSAIDs are attached to the organometallic moieties via monodentate (pyridine/phosphine) or bidentate (bipyridine) ligands, affording piano-stool Ru(II) and Os(II) arene complexes of general formula [M(η6-p-cymene)Cl2(N)], where N is a pyridine-based ligand, {2-(2-(1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl)acetoxy)ethyl-3-(pyridin-3-yl)propanoate} or {2-(2-(2-((2,6-dichlorophenyl)amino)phenyl)acetoxy)ethyl-3-(pyridin-3-yl)propanoate}, [M(η6-p-cymene)Cl2(P)], where P is a phosphine ligand, {2-(2-(1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl)acetoxy)ethyl-4-(diphenylphosphanyl)benzo...

Nonsteroidal Anti-inflammatory-Organometallic Anticancer Compounds

Pyridine- and phosphine-based ligands modified with ethacrynic acid (a broad acting glutathione transferase inhibitor) were prepared and coordinated to ruthenium(II)–arene complexes and to a ruthenium(III) NAMI-A type complex. All the compounds (ligands and complexes) were fully characterized by analytical and spectroscopic methods and, in one case, by single-crystal X-ray diffraction. The in vitro anticancer activity of the compounds was studied, with the compounds displaying moderate cytotoxicity toward the human ovarian cancer cell lines. All the complexes led to similar levels of residual GST activity in the different cell lines, irrespective of the stability of the Ru–ligand bond.

/pdf/synthesis-and-antiproliferative-activity-of-new-ruthenium-3i2sxuvyqc.pdf

Synthesis and Antiproliferative Activity of New Ruthenium Complexes with Ethacrynic-Acid-Modified Pyridine and Triphenylphosphine Ligands

Uncommon examples of coordination compounds of high valent transition metals with α-diimines were obtained and characterized by IR and NMR spectroscopy, X-ray diffraction and/or DFT analysis The 1 : 1 molar reactions of NbF5 with a selection of α-diimines afforded the ionic compounds [NbF4(DADR)2][NbF6] (DADR = DADDip, 1a; DADXyl, 1b; DADMes, 1c) in 80–90% yields The addition of DADDip to NbOCl3 gave NbOCl3(DADDip), 7 (62% yield) [MBr4(DADDip)][MBr6] (M = Nb, 7a; M = Ta, 7b) were afforded in moderate yields from MBr5 and DADDip The reactions of NbCl5 with DADDip and DADXyl proceeded with non-selective activation of the organic substrate affording complex mixtures of products, including the quinoxalinium salt [{2,6-C6H3(CHMe2)2}N(CH)2NCC(CHMe2)(CH)3C][NbCl6], 2, the Nb(IV) coordination complex NbCl4(DADDip), 3, the N-(monoprotonated) α-diimine salts [DADDip(H)][MCl6], 4a–b, and the iminomethyl-imidazolium [(2,6-C6H3Me2)NCHCHN(2,6-C6H3Me2)CCHN(2,6-C6H3Me2)][NbCl6], 5

Stable coordination complexes of α-diimines with Nb(v) and Ta(v) halides.

Examining Trichloroisocyanuric Acid and Oxalyl Chloride in Complementary Approaches to Fluorination of Group 15 Heteroatoms

A synthetic method for the palladium-catalyzed cyanation of aryl boronic acids using bench stable and non-toxic Ncyanosuccinimide has been developed. High-throughput experimentation facilitated the screen of 90 different ligands and the resultant statistical data analysis identified that ligand σ–donation, π–acidity and sterics are key drivers that govern yield. Categorization into three ligand groups – monophosphines, bisphosphines and miscellaneous – was performed before the analysis. For the monophosphines, the yield of the reaction increases for strong σ–donating, weak π–accepting ligands, with flexible pendant substituents. For the bisphosphines, the yield predominantly correlates with ligand lability. The applicability of the designed reaction to a wider substrate scope was investigated, showing good functional group tolerance in particular with boronic acids bearing electron-withdrawing substituents. This work outlines the development of a novel reaction, coupled with a fast and efficient workflow to gain understanding of the optimal ligand properties for the design of improved palladium cross-coupling catalysts.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/hlca.202100200

Development and Molecular Understanding of a Pd-catalyzed Cyanation of Aryl Boronic Acids Enabled by High-Throughput Experimentation and Data Analysis

The full potential of a high valent metal chloride as both a chlorinating and an oxidative agent was explored by allowing WCl6 to react with N-(2,6-diisopropylphenyl) α-diimines, in CH2Cl2 at room temperature. These α-diimines underwent unprecedented conversion to quinoxalinium cations via intramolecular C–N coupling.

/pdf/allowing-the-direct-interaction-of-n-aryl-a-diimines-with-a-246ju63fm3.pdf

Niccolò Bartalucci

Papers

Synthesis and Antiproliferative Activity of New Ruthenium Complexes with Ethacrynic-Acid-Modified Pyridine and Triphenylphosphine Ligands

Stable coordination complexes of α-diimines with Nb(v) and Ta(v) halides.

Examining Trichloroisocyanuric Acid and Oxalyl Chloride in Complementary Approaches to Fluorination of Group 15 Heteroatoms

Development and Molecular Understanding of a Pd-catalyzed Cyanation of Aryl Boronic Acids Enabled by High-Throughput Experimentation and Data Analysis

Allowing the direct interaction of N-aryl α-diimines with a high valent metal chloride: one-pot WCl6-promoted formation of quinoxalinium salts