Metal phosphine complexes incorporating alkyl substituents with ethane and ethylene backbones

Abstract The new chelating bis-phosphine ligands 1,2-bis(butylphenylphosphino)ethane (bppe) and cis-1,2-bis(butylphenylphosphino)ethylene (bppey) have been synthesised by (i) a one-pot synthesis from Ph2PBu and Li/dihalo alkyl, (ii) the reaction of 1,2-bis(diphenylphosphino)ethane (dppe) or cis-1,2- bis(diphenylphosphino)ethylene (dppey) and Li/n-BuCl and, (iii) in the case of bppe by sequential synthesis (all intermediates were isolated) from Ph2PBu via PhBuPLi and Ph2PH. bppe and bppey as well as the new lithium phosphide [(TMEDA)•LiPPh(Bu)]2 (17) were fully characterised by multinuclear NMR spectroscopy, mass spectrometry and, in the case of [(TMEDA)•LiPPh(Bu)]2 (17), by X-ray crystallography. Reaction of the bis-phosphines bppe and bppey with suitable metal precursors yielded the corresponding metal complexes: [PdCl2(bppe)] (18), [Pd(bppe)2](ClO4)2 (20), [(AuCl)2(bppe)] (21a), [(AuCl)2(bppey)] (21b), [Au(bppe)2]Cl (22a), [Au(bppey)2]Cl (22b), [(AgNO3)2(bppe)] (23) and [Au(bppe)2]ClO4 (24) in moderate to good yields. All were characterised by multinuclear NMR spectroscopy and mass spectrometry, while 18 and 20 were further characterised by X-ray crystallography. Preliminary stability tests showed, that of all new metal complexes only 18, 20 and 22a were adequately stable to justify further tests for anti-tumour activity. The cationic complexes 20 and 22a showed activity against HeLa cells while the neutral complex 18 was not active. A comparison with the previously investigated analogous dppe and dppey complexes revealed that 20 and 22a were found to be less active as a result of the replacement of a Ph groups with butyl groups in the phosphine ligand

Photo-and thermoresponsive N-salicylideneaniline derivatives : solid-state studies and structural aspects

Electronic supplementary information (ESI) available. CCDC 1899401, 1902658, 1966932, 1989369, 1989398, 1989403, 2014911, 2014914, 2019418, 2049690, 2049691, 2062423, 2157376, 2156456–2156467 and 2191107–2191119. For ESI and crystallographic data in CIF or other electronic format see DOI: https://doi. org/10.1039/d1nj03056f.N-Salicylideneaniline (SA) and its derivatives are known to possess chromism upon exposure to external stimuli. Herein, we present mechanochemical synthesis of a series of photo-and thermoresponsive SA-derivatives and report on solid-state stabilisation of their tautomeric forms either by change in temperature or by photoirradiation. The influence of UV light on proton transfer between the enol-imine (EI) and keto-amine (KA) forms was investigated at λ1 = 254 and λ2 = 365 nm. Differential scanning calorimetry (DSC) measurements provided extra information on the thermodynamic relationship between the prototropic tautomers, and their exposition to liquid nitrogen, combined with variable temperature single-crystal X-ray diffraction (VT-SCXRD) and spectroscopic data, ascertained structural reasons for the intrinsic thermo-optical properties of the compounds. A series of structural determinations between 150 and 300 K further shed light on the thermomechanical behaviour exhibited by the thermoresponsive compounds. By virtue of calorimetry we were able to demonstrate proton transfer via the intramolecular O⋯N hydrogen bond over the temperature range 193–453 K. This present work demonstrates the importance of applying complementary analytical techniques and appropriate approaches for understanding the switching behaviour between the EI and KA forms. Furthermore, the assertion that it is predominantly the planarity (φ < 25°) that determines thermochromaticity is questioned.The National Research Foundation (NRF), South Africa and Rhodes University Research Council.http://rsc.li/njchj2023Chemistr

Coumarin-Annulated Ferrocenyl 1,3-Oxazine Derivatives Possessing In Vitro Antimalarial and Antitrypanosomal Potency

A tailored series of coumarin-based ferrocenyl 1,3-oxazine hybrid compounds was synthesized and investigated for potential antiparasitic activity, drawing inspiration from the established biological efficacy of the constituent chemical motifs. The structural identity of the synthesized compounds was confirmed by common spectroscopic techniques: NMR, HRMS and IR. Biological evaluation studies reveal that the compounds exhibit higher in vitro antiparasitic potency against the chemosensitive malarial strain (3D7 P. falciparum) over the investigated trypanosomiasis causal agent (T. b. brucei 427) with mostly single digit micromolar IC50 values. When read in tandem with the biological performance of previously reported structurally similar non-coumarin, phenyl derivatives (i.e., ferrocenyl 1,3-benzoxazines and α-aminocresols), structure-activity relationship analyses suggest that the presence of the coumarin nucleus is tolerated for biological activity though this may lead to reduced efficacy. Preliminary mechanistic studies with the most promising compound (11b) support hemozoin inhibition and DNA interaction as likely mechanistic modalities by which this class of compounds may act to produce plasmocidal and antitrypanosomal effects

Synthesis, characterization and biological activity of some Dithiourea Derivatives:

Novel dithiourea derivatives have been designed as HIV-1 protease inhibitors using Autodock 4.2, synthesized and characterized by spectroscopic methods and microanalysis

Synthesis, structure and in vitro anti-trypanosomal activity of non-toxic Arylpyrrole-Based Chalcone derivatives:

With an intention of identifying chalcone derivatives exhibiting anti-protozoal activity, a cohort of relatively unexplored arylpyrrole-based chalcone derivatives were synthesized in moderate to good yields. The resultant compounds were evaluated in vitro for their potential activity against a cultured Trypanosoma brucei brucei 427 strain. Several compounds displayed mostly modest in vitro anti-trypanosomal activity with compounds 10e and 10h emerging as active candidates with IC50 values of 4.09 and 5.11 µM, respectively. More importantly, a concomitant assessment of their activity against a human cervix adenocarcinoma (HeLa) cell line revealed that these compounds are non-toxic

Cinnamoyl-Oxaborole Amides: Synthesis and Their in Vitro Biological Activity.

Due to the increased interest in their application in the treatment of infectious diseases, boron-containing compounds have received a significant coverage in the literature. Herein, a small set of novel cinnamoly-oxaborole amides were synthesized and screened against nagana Trypanosoma brucei brucei for antitrypanosomal activity. Compound 5g emerged as a new hit with an in vitro IC50 value of 0.086 μM against T. b. brucei without obvious inhibitory activity against HeLa cell lines. The same series was also screened against other human pathogens, including Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), for which moderate to weak activity (10 to >125 μM) was observed. Similarly, these compounds exhibited moderate activity against the human protozoal pathogen Trichomonas vaginalis with no observed effect on common microbiome bacterial species. The cross-species inhibitory activity presents the possibility of these compounds serving as broad-spectrum antibiotics for these prevalent three human pathogens

Novobiocin–ferrocene conjugates possessing anticancer and antiplasmodial activity independent of HSP90 inhibition.

A series of tailored novobiocin–ferrocene conjugates was prepared in moderate yields and investigated for in vitro anticancer and antiplasmodial activity against the MDA-MB-231 breast cancer line and Plasmodium falciparum 3D7 strain, respectively. While the target compounds displayed moderate anticancer activity against the breast cancer cell line with IC50 values in the mid-micromolar range, compounds 10a–c displayed promising antiplasmodial activity as low as 0.889 µM. Furthermore, the most promising compounds were tested for inhibitory effects against a postulated target, heat shock protein 90 (Hsp90)

Unexpected transformations of 3-(bromoacetyl)coumarin provides new evidence for the mechanism of thiol mediated dehalogenation of α-halocarbonyls

publisher versionThe mechanism for the thiol mediated dehalogenation of α-halogenated carbonyls has remained an unresolved problem, despite its ongoing application in synthetic organic chemistry. Nakamura and co-workers first proposed that net dehalogenation occurs via sequential nucleophilic substitutions, while Israel and co-workers concluded that the rate at which dehalogenation occurred suggested that dehalogenation proceeds in a single concerted step. In this study, we investigated the debromination and nucleophilic substitution of 3-(bromoacetyl)coumarin with a variety of thiophenols, whose electron donating or withdrawing natures resulted in large variations in the degree of nucleophilic substitution and dehalogenation products, respectively. Results from these experiments, in addition to an unexpected formation of thioether containing dibenzo[b,d]pyran-6-ones from a Robinson annulation, has provided new evidence for this disputed mechanism

Enhanced Catalytic Activity of a Copper(II) Metal–Organic Framework Constructed <i>via</i> Semireversible Single-Crystal-to-Single-Crystal Dehydration

Herein, we present a copper(II) metal–organic framework, [Cu2(btec)(OH2)4]·2H2O (1) [(btec)4– = 1,2,4,5-benzenetetracarboxylate], that undergoes single-crystal-to-single-crystal transformations into two anhydrous phases 2′ and 2″ with the chemical formula [Cu2(btec)], triggered by two-step dehydration at 403 and 433 K, respectively. After immersion in water for 3 days at room temperature, 2′ transformed into [Cu2(btec)(OH2)] (3), while both 2′ and 2″ took 1 week to revert to 1. Dynamic vapor sorption studies validated water-induced reversible structural transformations at 70% relative humidity (RH). According to single-crystal X-ray diffraction (SC-XRD), the local coordination geometry of the Cu2+ ion in 2′ changed from a saturated octahedron to a coordinatively unsaturated square-based pyramid in 3, manifested by changes in color and dimensionality. From a topological point of view, all of the scaffolds show a binodal (3,6)-connected kgd topology with the point symbol {43}2{46}. In addition, the materials were thoroughly characterized using routine spectroscopic data and various analytical techniques. The catalytic activity of the microporous materials in the liquid-phase oxidation of styrene in acetonitrile, using 30% (wt) H2O2 as the oxidant, was investigated. The excellent performance of the monohydrous phase 3 was shown to be superior to the pristine framework and the anhydrous counterparts, as evidenced by a good turnover number (TON) and turnover frequency (TOF) = 82.6 and 21.0 h–1, respectively. Within 4 h, the substrates were catalytically oxidized to the desired products with up to 67% conversion and 100% benzaldehyde selectivity. It is worth noting that the accessible active metal sites and higher surface area enhanced the catalytic properties of 3. Furthermore, the maintenance of catalytic efficiency over five cycles and reusability are illustrated and discussed in terms of the structural differences of the microporous frameworks. Thus, a preliminary reaction mechanism for the selective oxidation of styrene is proposed. This study not only provides a fascinating example of MOF chromism achieved by thermal activation and rehydration but also sheds some light on the relationship between pore-surface- or metal-engineered sites in MOFs and their heterogeneous catalytic performances

Enhanced Catalytic Activity of a Copper(II) Metal–Organic Framework Constructed <i>via</i> Semireversible Single-Crystal-to-Single-Crystal Dehydration

Herein, we present a copper(II) metal–organic framework, [Cu2(btec)(OH2)4]·2H2O (1) [(btec)4– = 1,2,4,5-benzenetetracarboxylate], that undergoes single-crystal-to-single-crystal transformations into two anhydrous phases 2′ and 2″ with the chemical formula [Cu2(btec)], triggered by two-step dehydration at 403 and 433 K, respectively. After immersion in water for 3 days at room temperature, 2′ transformed into [Cu2(btec)(OH2)] (3), while both 2′ and 2″ took 1 week to revert to 1. Dynamic vapor sorption studies validated water-induced reversible structural transformations at 70% relative humidity (RH). According to single-crystal X-ray diffraction (SC-XRD), the local coordination geometry of the Cu2+ ion in 2′ changed from a saturated octahedron to a coordinatively unsaturated square-based pyramid in 3, manifested by changes in color and dimensionality. From a topological point of view, all of the scaffolds show a binodal (3,6)-connected kgd topology with the point symbol {43}2{46}. In addition, the materials were thoroughly characterized using routine spectroscopic data and various analytical techniques. The catalytic activity of the microporous materials in the liquid-phase oxidation of styrene in acetonitrile, using 30% (wt) H2O2 as the oxidant, was investigated. The excellent performance of the monohydrous phase 3 was shown to be superior to the pristine framework and the anhydrous counterparts, as evidenced by a good turnover number (TON) and turnover frequency (TOF) = 82.6 and 21.0 h–1, respectively. Within 4 h, the substrates were catalytically oxidized to the desired products with up to 67% conversion and 100% benzaldehyde selectivity. It is worth noting that the accessible active metal sites and higher surface area enhanced the catalytic properties of 3. Furthermore, the maintenance of catalytic efficiency over five cycles and reusability are illustrated and discussed in terms of the structural differences of the microporous frameworks. Thus, a preliminary reaction mechanism for the selective oxidation of styrene is proposed. This study not only provides a fascinating example of MOF chromism achieved by thermal activation and rehydration but also sheds some light on the relationship between pore-surface- or metal-engineered sites in MOFs and their heterogeneous catalytic performances