Neutral rhenium(I) tricarbonyl complexes with sulfur-donor ligands: anti-proliferative activity and cellular localization.

Rhenium(I) tricarbonyl complexes are widely studied for their cell imaging properties and anti-cancer and anti-microbial activities, but the complexes with S-donor ligands remain relatively unexplored. A series of six fac-[Re(NN)(CO)3(SR)] complexes, where (NN) is 2,2'-bipyridyl (bipy) or 1,10-phenanthroline (phen), and RSH is a series of thiocarboxylic acid methyl esters, have been synthesized and characterized. Cellular uptake and anti-proliferative activities of these complexes in human breast cancer cell lines (MDA-MB-231 and MCF-7) were generally lower than those of the previously described fac-[Re(NN)(CO)3(OH2)]+ complexes; however, one of the complexes, fac-[Re(CO)3(phen)(SC(Ph)CH2C(O)OMe)] (3b), was active (IC50 ∼ 10 µM at 72 h treatment) in thiol-depleted MDA-MB-231 cells. Moreover, unlike fac-[Re(CO)3(phen)(OH2)]+, this complex did not lose activity in the presence of extracellular glutathione. Taken together these properties show promise for further development of 3b and its analogues as potential anti-cancer drugs for co-treatment with thiol-depleting agents. Conversely, the stable and non-toxic complex, fac-[Re(bipy)(CO)3(SC(Me)C(O)OMe)] (1a), predominantly localized in the lysosomes of MDA-MB-231 cells, as shown by live cell confocal microscopy (λex = 405 nm, λem = 470-570 nm). It is strongly localized in a subset of lysosomes (25 µM Re, 4 h treatment), as shown by co-localization with a Lysotracker dye. Longer treatment times with 1a (25 µM Re for 48 h) resulted in partial migration of the probe into the mitochondria, as shown by co-localization with a Mitotracker dye. These properties make complex 1a an attractive target for further development as an organelle probe for multimodal imaging, including phosphorescence, carbonyl tag for vibrational spectroscopy, and Re tag for X-ray fluorescence microscopy.

Rare Earths-The Answer to Everything.

Rare earths, scandium, yttrium, and the fifteen lanthanoids from lanthanum to lutetium, are classified as critical metals because of their ubiquity in daily life. They are present in magnets in cars, especially electric cars; green electricity generating systems and computers; in steel manufacturing; in glass and light emission materials especially for safety lighting and lasers; in exhaust emission catalysts and supports; catalysts in artificial rubber production; in agriculture and animal husbandry; in health and especially cancer diagnosis and treatment; and in a variety of materials and electronic products essential to modern living. They have the potential to replace toxic chromates for corrosion inhibition, in magnetic refrigeration, a variety of new materials, and their role in agriculture may expand. This review examines their role in sustainability, the environment, recycling, corrosion inhibition, crop production, animal feedstocks, catalysis, health, and materials, as well as considering future uses.

Gallium reactivates first and second generation quinolone antibiotics towards drug-resistant Klebsiella pneumoniae.

Herein, we report on a series of homoleptic [GaL3] and heteroleptic organometallic [GaMe2L] complexes of inactive quinolone antibiotics; nalidixic acid, oxolinic acid and norfloxacin with their antibacterial activity (MIC 0.024-0.781 µM) towards four multi-drug resistant strains of Klebsiella pneumoniae through complexation to gallium.

Correction: Catalytic exploration of NHC-Ag(I)HMDS complexes for the hydroboration and hydrosilylation of carbonyl compounds.

Correction for 'Catalytic exploration of NHC-Ag(I)HMDS complexes for the hydroboration and hydrosilylation of carbonyl compounds' by Claudia P. Giarrusso et al., Dalton Trans., 2023, 52, 7828-7835, https://doi.org/10.1039/D3DT01042B.

Direct Reaction - One Step Route to Synthesize Lanthanoid-iodide Formamidinates.

This paper describes a novel and simple method - direct reaction of lanthanoid metals with equimolar amounts of iodine and a formamidine under ultrasonication as an effective, metal-based route to lanthanoid(III) diiodide formamidinates, namely I. N,N'-Bis(2,6-diisopropylphenyl)formamidinatodiiodidolanthanoid(III) complexes [Ln(DippForm)I2 (thf)3 ] (Ln=La, 1, Ce, 2, Tb, 3, Ho, 4, Er, 5, Tm, 6); II. N,N'-Bis(2,6-diethylphenyl)formamidinatodiiodidolanthanoid(III) complexes [Ln(EtForm)I2 (thf)3 ] (Ln=Ce, 7, Nd, 8, Gd, 9, Tb, 10, Dy, 11, Ho, 12, Er, 13, Lu, 14). III. N,N'-bis(2,6-dimethylphenyl)formamidinatodiiodidolanthanoid(III) complexes [Ln(XylForm)I2 (thf)3 ] (Ln=Ce, 15, Nd, 16, Gd, 17, Tm, 18, Lu 19); IV. N,N'-bis(phenyl)formamidinatodiiodidolanthanoid complexes [Ln(PhForm)I2 (thf)3 ] (Ln=Nd, 20, Gd, 21, Er, 22). Compound [Ce(XylForm)2 I(thf)2 ] (23) was also synthesized by the same method except the ratio of I2 to XylFormH was 1 : 4. Divalent N,N'-bis(2,6-diisopropylphenyl)formamidinato-iodido-lanthanoid(II) complexes [Eu(DippForm)I(thf)4 ] ⋅ thf (24), [Yb(DippForm)I(thf)3 ] ⋅ 2DippFormH (25), [Sm(DippForm)I(thf)4 ] ⋅ thf (26) have also been synthesized by direct reactions of the free metals, iodine and DippFormH. Interestingly, [Sm(DippForm)I2 (thf)3 ] (27) was obtained by the oxidation of [Sm(DippForm)I(thf)4 ] ⋅ thf (26) on exposure to air. N,N'-Bis(2,6-dimethylphenyl)formamidinatoiodidosamarium(II) [Sm(XylForm)I(thf)3 ]n (28) was also prepared by direct reaction of Sm, iodine and XylFormH (mole ratio of I2 : XylFormH=1 : 2). All products have been identified by X-ray crystallography and all the trivalent complexes [Ln(Form)n I3-n ] (n=1 or 2) are stable to rearrangement.

Catalytic exploration of NHC-Ag(I)HMDS complexes for the hydroboration and hydrosilylation of carbonyl compounds.

The synthesis and full characterisation of two silver(I) amido complexes, stabilised by ancillary N-heterocyclic carbene (NHC) ligands is presented. The light stable complexes [Ag(IDipp)HMDS] 3 and [Ag(IAd)HMDS] 4 were explored as suitable pre-catalysts in the hydroboration and hydrosilylation of a range of carbonyl substrates, with complex 3 out-performing 4 and our previous phosphine-stabilised lead catalyst [Ag(PCy3)HMDS] 5. This study highlights that changing the stabilising Lewis donor in the silver(I)amide system has an influence on catalytic efficiency. Finally, to shed light on the catalytic differences of pre-catalysts 3-5, we used a suite of programs to examine the influence of steric bulk on the Lewis donor ligand including percent buried volume (%VBur), Solid-G and AtomAccess which revealed the most sterically protected Ag(I) metal centre correlated to the most effective pre-catalyst 3.

Synthesis and Characterisation of Novel Bis(diphenylphosphane oxide)methanidoytterbium(III) Complexes.

Reaction of [YbCp2(dme)] (Cp = cyclopentadienyl, dme = 1,2 dimethoxyethane) with bis(diphenylphosphano)methane dioxide (H2dppmO2) leads to deprotonation of the ligand H2dppmO2 and oxidation of ytterbium, forming an extremely air-sensitive product, [YbIII(HdppmO2)3] (1), a six-coordinate complex with three chelating (OPCHPO) HdppmO2 ligands. Complex 1 was also obtained by a redox transmetallation/protolysis synthesis from metallic ytterbium, Hg(C6F5)2, and H2dppmO2. In a further preparation, the reaction of [Yb(C6F5)2] with H2dppmO2, not only yielded compound 1, but also gave a remarkable tetranuclear cage, [Yb4(µ-HdppmO2)6(µ-F)6] (2) containing two [Yb(µ-F)]2 rhombic units linked by two fluoride ligands and the tetranuclear unit is encapsulated by six bridging HdppmO2 donors. The fluoride ligands of the cage result from C-F activation of pentafluorobenzene and concomitant formation of p-H2C6F4 and m-H2C6F4, the last being an unexpected product.

Europium is Different: Solvent and Ligand Effects on Oxidation State Outcomes and C-F Activation in Reactions Between Europium Metal and Pentafluorophenylsilver.

Unique outcomes have emerged from the redox transmetallation/ protolysis (RTP) reactions of europium metal with [Ag(C6 F5 )(py)] (py=pyridine) and pyrazoles (RR'pzH). In pyridine, a solvent not normally used for RTP reactions, the products were mainly EuII complexes, [Eu(RR'pz)2 (py)4 ] (RR'pz=3,5-diphenylpyrazolate (Ph2 pz) 1; 3-(2-thienyl)-5-trifluoromethylpyrazolate (ttfpz) 2; 3-methyl-5-phenylpyrazolate (PhMepz) 3). However, use of 3,5-di-tert-butylpyrazole (tBu2 pzH) gave trivalent [Eu(tBu2 pz)3 (py)2 ] 4, whereas the bulkier N,N'-bis(2,6-difluorophenyl)formamidine (DFFormH) gave divalent [Eu(DFForm)2 (py)3 ] 5. In tetrahydrofuran (thf), the usual solvent for RTP reactions, C-F activation was observed for the first time with [Ag(C6 F5 )(py)] in such reactions. Thus trivalent [{Eu2 (Ph2 pz)4 (py)4 (thf)2 (µ-F)2 }{Eu2 (Ph2 pz)4 (py)2 (thf)4 (µ-F)2 }] (6), [Eu2 (ttfpz)4 (py)2 (dme)2 (µ-F)2 ] (7), [Eu2 (tBu2 pz)4 (dme)2 (µ-F)2 ] (8) were obtained from the appropriate pyrazoles, the last two after crystallization from 1,2-dimethoxyethane (dme). Surprisingly 3,5-dimethylpyrazole (Me2 pzH) gave the divalent cage [Eu6 (Me2 pz)10 (thf)6 (µ-F)2 ] (9). This has a compact ovoid core held together by bridging fluoride, thf, and pyrazolate ligands, the last including the rare µ4 -1η5 (N2 C3 ): 2η2 (N,N'): 3κ(N): 4κ(N') pyrazolate binding mode. With the bulky N,N'-bis(2,6-diisopropylphenyl)formamidine (DippFormH), which often favours C-F activation in RTP reactions, neither oxidation to EuIII nor C-F activation was observed and [Eu(DippForm)2 (thf)2 ] (10) was isolated. By contrast, Eu reacted with Bi(C6 F5 )3 and Ph2 pzH or tBu2 pzH in thf without C-F activation, to give [Eu(Ph2 pz)2 (thf)4 ] (11) and [Eu(tBu2 pz)3 (thf)2 ] (12) respectively, the oxidation state outcomes corresponding to that for use of [Ag(C6 F5 )(py)] in pyridine.

A simple one-pot route to stable formamidinatoiodidolanthanoid(III) complexes from lanthanoid metals.

A number of formamidinatoiodidolanthanoid(III) complexes, [Ln(DFForm)2I(thf)2] and [Ln(DFForm)I2(thf)3] (DFFormH = N,N'-bis(2,6-difluorophenyl)formamidine) and [Ln(DippForm)I2(thf)3] (DippFormH = N,N'-bis(2,6-diisopropylphenyl)formamidine) have been synthesized in good yields by one-pot direct reactions of the corresponding free metals with iodine and DFFormH or DippFormH in suitable ratios and are stable to rearrangement.

Phase Transition and Coefficients of Thermal Expansion in Al2-xInxW3O12 (0.2 ≤ x ≤ 1).

Materials from theA2M3O12 family are known for their extensive chemical versatility while preserving the polyhedral-corner-shared orthorhombic crystal system, as well as for their consequent unusual thermal expansion, varying from negative and near-zero to slightly positive. The rarest are near-zero thermal expansion materials, which are of paramount importance in thermal shock resistance applications. Ceramic materials with chemistry Al2-xInxW3O12 (x = 0.2-1.0) were synthesized using a modified reverse-strike co-precipitation method and prepared into solid specimens using traditional ceramic sintering. The resulting materials were characterized by X-ray powder diffraction (ambient and in situ high temperatures), differential scanning calorimetry and dilatometry to delineate thermal expansion, phase transitions and crystal structures. It was found that the x = 0.2 composition had the lowest thermal expansion, 1.88 × 10-6 K-1, which was still higher than the end member Al2W3O12 for the chemical series. Furthermore, the AlInW3O12 was monoclinic phase at room temperature and transformed to the orthorhombic form at ca. 200 °C, in contrast with previous reports. Interestingly, the x = 0.2, x = 0.4 and x = 0.7 materials did not exhibit the expected orthorhombic-to-monoclinic phase transition as observed for the other compositions, and hence did not follow the expected Vegard-like relationship associated with the electronegativity rule. Overall, compositions within the Al2-xInxW3O12 family should not be considered candidates for high thermal shock applications that would require near-zero thermal expansion properties.

The thiol-based reduction of Bi(V) and Sb(V) anti-leishmanial complexes.

Low molecular weight thiols including trypanothione and glutathione play an important function in the cellular growth, maintenance and reduction of oxidative stress in Leishmania species. In particular, parasite specific trypanothione has been established as a prime target for new anti-leishmania drugs. Previous studies into the interaction of the front-line Sb(V) based anti-leishmanial drug meglumine antimoniate with glutathione, have demonstrated that a reduction pathway may be responsible for its effective and selective nature. The new suite of organometallic complexes, of general formula [MAr3(O2CR)2] (M = Sb or Bi) have been shown to have potential as new selective drug candidates. However, their behaviour towards the critical thiols glutathione and trypanothione is still largely unknown. Using NMR spectroscopy and mass spectrometry we have examined the interaction of the analogous Sb(V) and Bi(V) organometallic complexes, [SbPh3(O2CCH2(C6H4CH3))2] S1 and [BiPh3(O2CCH2(C6H4CH3))2] B1, with the trifluoroacetate (TFA) salt of trypanothione and L-glutathione. In the presence of trypanothione or glutathione at the clinically relevant pH of 4-5 for Leishmania amastigotes, both complexes undergo facile and rapid reduction, with no discernible difference. However, at a higher pH (6-7), the complexes behave quite differently towards glutathione. The Bi(V) complex is again reduced rapidly but the Sb(V) complex undergoes slow reduction over 8 h (t1/2 = 54 min.) These results give the first insights into why the highly oxidising Bi(V) complexes display low selectivity in their cytotoxicity towards leishmanial and mammalian cells, while the Sb(V) complexes show good selectivity.

Development of new combination anti-leishmanial complexes: Triphenyl Sb(V) mono-hydroxy mono-quinolinolates.

In seeking to develop single entity combination anti-Leishmanial complexes six heteropletic organometallic Sb(V) hydroxido quinolinolate complexes of general formula [SbPh3(C9H4NORR')(OH)] have been synthesised and characterised, derived from a series of halide substituted quinolinols (8-hydroxyquinolines). Single crystal X-ray diffraction on all the complexes show a common distorted six-coordinate octahedral environment at the Sb(V) centre, with the aryl groups and nitrogen atom of quinolinolate ligand bonding in the equatorial planes, with the two oxygen atoms (hydroxyl and quinolinolate) occupying the axial plane in an almost linear configuration. Each complex was tested for their anti-promastigote activity and mammalian cytotoxicity and a selectivity indices established. The complexes displayed excellent anti-promastigote activity (IC50: 2.03-3.39 µM) and varied mammalian cytotoxicity (IC50: 12.7-46.9 µM), leading to a selectivity index range of 4.52-16.7. All complexes displayed excellent anti-amastigote activity with a percentage infection range of 2.25%-9.00%. All complexes performed substantially better than the parent quinolinols and comparable carboxylate complexes [SbPh3(O2CRR')2] indicating the synergistic role of the Sb(V) and quinolinol moieties in increasing parasite mortality. Two of the complexes [SbPh3(C9H4NOBr2)(OH)] 4, [SbPh3(C9H4NOI2)(OH)] 5, provide an ideal combination of high selective and good activity towards the leishmanial amastigotes and offer the potential as good lead compounds.

Main Group Metal-Mediated Transformations of Imines.

Main-group-metal-mediated transformations of imines have earned a valued place in the synthetic chemist's toolbox. Their versatility allows the simple preparation of various nitrogen containing compounds. This review will outline the early discoveries including metallation, addition/cyclisation and metathesis pathways, followed by the modern-day use of imines in synthetic methodology. Recent advances in imine C-F activation protocols are discussed, alongside revisiting "classic" imine reactivity from a sustainable perspective. Developments in catalytic methods for hydroelementation of imines have been reviewed, highlighting the importance of s-block metals in the catalytic arena. Whilst stoichiometric transformations in alternative reaction media such as deep eutectic solvents or water have been summarised. The incorporation of imines into flow chemistry has received recent attention and is summarised within.

Widely contrasting outcomes from the use of tris(pentafluorophenyl)bismuth or pentafluorophenylsilver as oxidants in the reactions of lanthanoid metals with N,N'-diarylformamidines.

Reactions of lanthanoid metals with tris(pentafluorophenyl)bismuth or pentafluorophenylsilver and two widely disparate formamidines, N,N'-bis(2,6-difluorophenyl)formamidine (DFFormH) and N,N'-bis(2,6-diisopropylphenyl)formamidine (DippFormH) have been investigated as possible redox transmetallation/protolysis (RTP) syntheses of lanthanoid formamidinates. Thus, [Ln(DFForm)3(thf)] (Ln = Lu, 1, Yb, 2, Tm, 3, Er, 4, Ho, 5, Dy, 6; thf = tetrahydrofuran), [Ln(DFForm)3(thf)2] (Ln = Tb, 7, Gd, 8, Sm, 9, Nd, 10), and [Yb(DippForm)2(thf)2]·2thf (11) complexes were obtained from an excess of lanthanoid metals, [Bi(C6F5)3]·0.5diox (diox = 1,4-dioxane) and the appropriate formamidine. Reaction of neodymium and [Bi(C6F5)3]·0.5diox with the bulkier DippFormH in thf resulted in C-F activation and formation of [Nd(DippForm)2F(thf)2] (12) and o-HC6F4O(CH2)4N(Dipp)CH[double bond, length as m-dash]N(Dipp) (Dipp = 2,6-di-isopropylphenyl). Although the reaction of erbium and [Bi(C6F5)3]·0.5diox with DippFormH was not complete after one week (by 19F NMR), use of [Hg(C6F5)2] instead of [Bi(C6F5)3]·0.5diox resulted in C-F activation and formation of [Er(DippForm)2F(thf)] (13) and o-HC6F4O(CH2)4N(Dipp)CH[double bond, length as m-dash]N(Dipp) in two days. Attempted RTP reactions between lanthanoid metals, AgC6F5 and DFFormH in thf gave [Ag2(DFForm)2]·3thf (14), except in the case of ytterbium. All other lanthanoid metals required activation by I2 (2%) before lanthanoid complex formation could be achieved. From these reactions, lanthanoid formamidinates, [Ln(DFForm)2(solv)I] (Ln = Lu, 15, Tm, 16, Er, 17, Tb, 18, Gd, 19), [Ln(DFForm)3(py)] (Ln = Er, 17a, Tb, 18a; py = pyridine), and [Nd(DFForm)3(thf)2]·thf (10) were obtained. Where two types of lanthanoid formamidinates [Ln(DFForm)3(py)] and [Ln(DFForm)2(solv)I] were obtained from the Ln metals activated by I2, they could not be separated on preparative scale. From Yb, the peroxide-bridged complex, [Yb2(DippForm)2(O2)2(py)4] (20) was surprisingly isolated. Thus [Bi(C6F5)3]·0.5diox has potential as an oxidative replacement for diarylmercurials in RTP syntheses of lanthanoid formamidinates but [AgC6F5(py)] does not.

Isomers of Alkali Metal (Methylbenzyl)allylamides: A Theoretical Perspective.

Recent studies of alkali metal N-(α-methylbenzyl)allylamides containing lithium, sodium, and potassium have shown unique rearrangements in NMR experiments. It was found that lithium isomers favored the formation of aza-allyl and aza-enolate complexes that could exist in a solution for a substantial amount of time. As the radius of the metal ion increases going from lithium to potassium, so does the preference for the formation of the imine structure. For sodium, the aza-allyl complex could still be isolated, whereas the imine structure was only found to be stable on the scale of several hours for potassium. In this work, ab initio calculations were used to shed light on this phenomenon. Decomposition of intermolecular interaction energies of the aza-allyl, aza-enolate, and imine complexes showed that for lithium, the formation of aza-allyl and aza-enolate complexes was driven by electrostatic interactions. For potassium, the dispersion component of the metal interaction with the ligand proved to be more important for the stability of the imine structure. The presence of the imine formation in potassium and partially in sodium was found to be due to the reduced electrostatic nature of these larger metals. The assignment of the experimental NMR spectra was further confirmed with the natural bond order (NBO) analysis as well as the partial charge calculations. Analysis of orbital energies, specifically those of the highest occupied molecular orbitals (HOMOs), as well as the deformation energies of each of the ligands, were also considered. Through these procedures, an understanding of the tendency for each metal to have a unique isomerization pathway was gained.

Structural Elucidation of Silver(I) Amides and Their Application as Catalysts in the Hydrosilylation and Hydroboration of Carbonyls.

This study details the isolation and characterisation of three novel silver(I) amides in solution and solid-state, [Ag(Cy3 P)(HMDS)] 2, [Ag(Cy3 P){N(TMS)(Dipp)}] 3 and [Ag(Cy3 P)2 (NPh2 )] 4. Their catalytic abilities have proved successful in hydroboration and hydrosilylation reactions with a full investigation performed with complex 2. Both protocols proceed under mild conditions, displaying exceptional functional-group tolerance and chemoselectivity, in excellent conversions at competitive reaction times. This work reveals the first catalytic hydroboration of aldehydes and ketones performed by a silver(I) catalyst.

Ruthenium(II)-Arene Thiocarboxylates: Identification of a Stable Dimer Selectively Cytotoxic to Invasive Breast Cancer Cells.

RuII -arene complexes provide a versatile scaffold for novel anticancer drugs. Seven new RuII -arene-thiocarboxylato dimers were synthesized and characterized. Three of the complexes (2 a, b and 5) showed promising antiproliferative activities in MDA-MB-231 (human invasive breast cancer) cells, and were further tested in a panel of fifteen cancerous and noncancerous cell lines. Complex 5 showed moderate but remarkably selective activity in MDA-MB-231 cells (IC50 =39±4 µm Ru). Real-time proliferation studies showed that 5 induced apoptosis in MDA-MB-231 cells but had no effect in A549 (human lung cancer, epithelial) cells. By contrast, 2 a and b showed moderate antiproliferative activity, but no apoptosis, in either cell line. Selective cytotoxicity of 5 in aggressive, mesenchymal-like MDA-MB-231 cells over many common epithelial cancer cell lines (including noninvasive breast cancer MCF-7) makes it an attractive lead compound for the development of specifically antimetastatic Ru complexes with low systemic toxicity.

Anti-leishmanial activity and cytotoxicity of a series of tris-aryl Sb(V) mandelate cyclometallate complexes.

A series of ten cyclometallates and two µ2-peroxo bridged tris-aryl Sb(V) complexes derived from R/S-mandelic acid (= R/S-ManH2) were synthesised and characterised. As confirmed by X-ray crystallography the complexes 1Sr/s, [Sb(o-tol)3(man)], 2Sr/s, [Sb(m-tol)3(man)], 4Sr/s, [Sb(o-PhOMe)3(man)], 5Sr/s, [Sb(Mes)3(man)] and 6Sr/s, [Sb(p-tert-BuPh)3(man)] are all cyclometallates. Complexes 3Sr/s, [(Sb(p-tol)3(manH)2O2], contain a bridging O22- anion in the solid-state but convert to the cyclometallates in DMSO solution with concomitant release of H2O2 and formation of complexes [Sb(p-tol)3(man)], 3Sr'/s'. All complexes underwent initial testing against both human fibroblasts and L. major V121 promastigotes. IC50 values were found to range from 2.07 (6Sr) to >100 (4Sr) µM and 0.21 (5Ss) to >100 (4Ss) µM for fibroblasts and parasites respectively. Two of the complexes were found to be ineffective, displaying no toxicity (4S/r). Despite the degree of mammalian toxicity, the selectivity of most complexes exceeded an SI of three and so were assessed for their anti-amastigote activity. Excellent anti-amastigote activity was observed for complexes at both 10 µM and 5 µM, with percentage infection value ranging from 0.15-3.00% for those tested at 10 µM and 0.25-2.50% for those at 5 µM.

Alkyl gallium(III) quinolinolates: A new class of highly selective anti-leishmanial agents.

A series of eight alkyl gallium complexes of general formulae [GaMe2(L)] and [Ga(Me)2L] have been synthesised, characterised and their antimicrobial activity against bacteria, cancer cells and Leishmania assessed. All eight complexes are novel, with the solid-state structures of all complexes successfully authenticated by single crystal X-ray diffraction. The dimethyl complexes all adopt a four-coordinate tetrahedral confirmation, while the monomethyl complexes are five-coordinate trigonal bipyramidal. All complexes were screened for their anti-bacterial activity either by solution state diffusion, or a solid-state stab test. The five soluble complexes underwent testing against two differing mammalian cell controls, with excellent selectivity observed against COS-7 cells, with an IC50 range of 88.5 µM to ≥100 µM. Each soluble complex was also tested for their anti-cancer capabilities, with no significant activity observed. Excellent activity was exhibited against the protozoan parasite Leishmania major (strain: V121) in both the promastigote and amastigote forms, with IC50 values ranging from 1.11 µM-13.4 µM for their anti-promastigote activity and % infection values of 3.5% ± 0.65-11.5% ± 0.65 for the more clinically relevant amastigote. Selectivity indices for each were found to be in the ranges of 6.61-64.7, with significant selectivity noted for two of the complexes. At minimum, the gallium complexes show a 3-fold enhancement in activity towards the Leishmaniaamastigotes over the parent quinolinols alone.

Lithium-Bromide Exchange versus Nucleophilic Addition of Schiff's base: Unprecedented Tandem Cyclisation Pathways.

By exploring lithium-bromide exchange reactivity of aromatic Schiff's bases with tert-butyllithium (tBuLi), we have revealed unprecedented competitive intermolecular and intramolecular cascade annulation pathways, leading to valuable compounds, such as iso-indolinones and N-substituted anthracene derivatives. A series of reaction parameters were probed, including solvent, stoichiometry, sterics and organolithium reagent choice, in order to understand the influences that limit such ring-closing pathways. With two viable reactivity options for the organolithium on the imine; namely, nucleophilic addition or lithium-bromide exchange, a surprising competitive nature was observed, where nucleophilic addition dominated, even under cryogenic conditions. Considering the most commonly used solvents for lithium-bromide exchange, tetrahydrofuran (THF) and diethyl ether (Et2 O), contrasting reactivity outcomes were revealed with nucleophilic addition promoted in THF, while Et2 O yielded almost double the conversion of cyclic products than in THF.