Identification of the Target for a Transition Metal-α-Amino Acid Complex Antibiotic Against Mycobacterium smegmatis.

Spontaneous mutants of Mycobacterium smegmatis strain mc2155 resistant to 1-PG (iridium-L-phenylglycine complex), an antimycobacterial antibiotic, were isolated. Based on the discovery that some 1-PG-resistant mutants (1-PG R ) were also resistant to high concentrations of clarithromycin (≥250 µg/ml), but no other anti-mycobacterial antibiotics, the 23S rRNA region spanning the peptidyl transferase domain was sequenced and mutations shown to be localized in the peptidyl transferase domain of the 23S rRNA gene. Measurements showed that 1-PG bound to ribosomes isolated from the 1-PG-sensitive parental strain, but the ribosome binding values for the 1-PG R mutant reduced.

Synthesis, Characterization, and Non-Covalent Interactions of Palladium(II)-Amino Acid Complexes.

The reaction of palladium(II) acetate with acyclic amino acids in acetone/water yields square planar bis-chelated palladium amino acid complexes that exhibit interesting non-covalent interactions. In all cases, complexes were examined by multiple spectroscopic techniques, especially HRMS (high resolution mass spectrometry), IR (infrared spectroscopy), and 1H NMR (nuclear magnetic resonance) spectroscopy. In some cases, suitable crystals for single crystal X-ray diffraction were able to be grown and the molecular structure was obtained. The molecular geometries of the products are discussed. Except for the alanine complex, all complexes incorporate water molecules into the extended lattice and exhibit N-H···O and/or O···(HOH)···O hydrogen bonding interactions. The non-covalent interactions are discussed in terms of the extended lattice structures exhibited by the structures.

Noble Metal Organometallic Complexes Display Antiviral Activity against SARS-CoV-2.

SARS-CoV-2 emerged in 2019 as a devastating viral pathogen with no available preventative or treatment to control what led to the current global pandemic. The continued spread of the virus and increasing death toll necessitate the development of effective antiviral treatments to combat this virus. To this end, we evaluated a new class of organometallic complexes as potential antivirals. Our findings demonstrate that two pentamethylcyclopentadienyl (Cp*) rhodium piano stool complexes, Cp*Rh(1,3-dicyclohexylimidazol-2-ylidene)Cl2 (complex 2) and Cp*Rh(dipivaloylmethanato)Cl (complex 4), have direct virucidal activity against SARS-CoV-2. Subsequent in vitro testing suggests that complex 4 is the more stable and effective complex and demonstrates that both 2 and 4 have low toxicity in Vero E6 and Calu-3 cells. The results presented here highlight the potential application of organometallic complexes as antivirals and support further investigation into their activity.

Crystal structures of (η4-cyclo-octa-1,5-diene)bis(1,3-di-methyl-imidazol-2-yl-idene)iridium(I) iodide and (η4-cyclo-octa-1,5-diene)bis-(1,3-di-ethyl-imidazol-2-yl-idene)iridium(I) iodide.

The title complexes, (η4-cyclo-octa-1,5-diene)bis-(1,3-di-methyl-imidazol-2-yl-idene)iridium(I) iodide, [Ir(C5H8N2)2(C8H12)]I, (1) and (η4-cyclo-octa-1,5-di-ene)bis-(1,3-di-ethyl-imidazol-2-yl-idene)iridium(I) iodide, [Ir(C7H12N2)2(C8H12)]I, (2), were prepared using a modified literature method. After carrying out the oxidative addition of the amino acid l-proline to [Ir(COD)(IMe)2]I in water and slowly cooling the reaction to room temperature, a suitable crystal of 1 was obtained and analyzed by single-crystal X-ray diffraction at 100 K. Although this crystal structure has previously been reported in the Pbam space group, it was highly disordered and precise atomic coordinates were not calculated. A single crystal of 2 was also obtained by heating the complex in water and letting it slowly cool to room temperature. Complex 1 was found to crystallize in the monoclinic space group C2/m, while 2 crystallizes in the ortho-rhom-bic space group Pccn, both with Z = 4.

Iridium piano stool complexes with activity against S. aureus and MRSA: it is past time to truly think outside of the box.

A new class of piano-stool iridium complexes with 1,2-diaminoethane ligands are shown to be effective and safe antimicrobials with activity against Staphylococcus aureus, including various isolates of methicillin-resistant strains (MRSA). Comparison to other piano stool complexes with activity against mycobacteria are made along with a discussion of structure-activity relationships. The structures of one the most active complexes with the ligand cis-1,2-diaminocyclohexane and one of the least active complexes with the ligand trans-1,2-diaminocyclohexane are compared and discussed with respect to their drastically different activities. In vitro toxicity studies for all of the complexes are described. In addition, a mouse study with one of the complexes, [(pentamethylcyclopentadienyl)(cis-1,2-diaminocyclohexane)(chloro)iridium]chloride, showed no ill effects on the mice at high doses.

Octametallic Cluster of Cp*Ir(glycinato) Cations.

Removal of chloride from Cp*Ir(glycinato)Cl in noncoordinating solvents with Ag[PF6] or Tl[PF6] leads to the formation of a closed octametallic loop of cations. The same loop also sequesters a number of PF6 - counter anions. This is in contrast with reports that piano-stool complexes with amino acids form only trimetallic [Cp*Ir(aminoacidato)]3 3+ moieties upon creating the cation. Cp*Ir(glycinato)Cl also forms a trimetallic compound as well as a octametallic compound, and the octametallic vs trimetallic formation appears to be dependent on the anion. The synthesis and characterization of the octametallic complex, as well as some monometallic and trimetallic compounds, are reported, including the X-ray crystal structures.

mer-Tri-chlorido-tris-(tetra-hydro-thio-phene-κS)iridium(III): preparation and comparison with other mer-tri-chlorido-tris-(tetra-hydro-thio-phene-κS)metal complexes.

The title complex, [IrCl3(C4H8S)3], was prepared according to a literature method. A suitable crystal was obtained by diffusion of pentane into a di-chloro-methane solution and analyzed by single-crystal X-ray diffraction at 100 K. The title complex is isotypic with mer-tri-chlorido-tris-(tetra-hydro-thio-phene-κS)rhodium(III). However, the orientation of the tetra-hydro-thio-phene rings is different from an earlier report of mer-tri-chlorido-tris-(tetra-hydro-thio-phene-κS)iridium(III) deposited in the Cambridge Structural Database. The IrS3Cl3 core shows a nearly octa-hedral structure with various bond angles within 1-2° of the perfect 90 or 180° expected for an octa-hedron. The structure of the title compound is compared with the previous iridium complex as well as the rhodium and other octa-hedral metal tris-tetra-hydro-thio-phene compounds previously structurally characterized. DFT calculations were performed, which indicate the mer isomer is significantly lower in energy than the fac isomer by 50.1 kJ mol-1, thereby accounting for all compounds in the CSD being of the mer geometry. Powder X-ray diffraction of the bulk material showed that the preparation method yielded only the isomorph reported in this communication.

Serendipitous preparation of fac-(aceto-nitrile-κN)tri-chlorido-[(1,2,5,6-η)-cyclo-octa-1,5-diene]iridium(III).

A reaction between [(COD)IrCl]2 (COD is cyclo-octa-1,5-diene), HCl and indene failed to provide the hoped for chlorido-indenyliridium dimer, but instead produced the title compound, [IrCl3(CH3CN)(C8H12)], which is an octa-hedral complex of iridium(III) with a chelating cyclo-octa-1,5-diene ligand, three chloride ligands in a fac arrangement, and one aceto-nitrile ligand. Attempts to devise a rational synthesis for the title compound were unsuccessful.

Crystal structure of di-µ-chlorido-bis-[di-chlorido-bis-(methanol-κO)iridium(III)] dihydrate: a surprisingly simple chlorido-iridium(III) dinuclear complex with methanol ligands.

The reaction between IrCl3·xH2O in methanol led to the formation of small amounts of the title compound, [Ir2Cl6(CH3OH)4]·2H2O, which consists of two IrCl4O2 octa-hedra sharing an edge via chloride bridges. The mol-ecule lies across an inversion center. Each octa-hedron can be envisioned as being comprised of four chloride ligands in the equatorial plane with methanol ligands in the axial positions. A lattice water mol-ecule is strongly hydrogen-bonded to the coordinating methanol ligands and weak inter-actions with coordinating chloride ligands lead to the formation of a three-dimensional network. This is a surprising structure given that, while many reactions of iridium chloride hydrate are carried out in alcoholic solvents, especially methanol and ethanol, this is the first structure of a chloridoiridium compound with only methanol ligands.

Crystal structures of fac-tri-chlorido-tris-(tri-methyl-phosphane-κP)rhodium(III) monohydrate and fac-tri-chlorido-tris-(tri-methyl-phosphane-κP)rhodium(III) methanol hemisolvate: rhodium structures that are isotypic with their iridium analogs.

The crystal structures of two solvates of fac-tri-chlorido-tris-(tri-methyl-phosphane-κP)rhodium(III) are reported, i.e. one with water in the crystal lattice, fac-[RhCl3(Me3P)3]·H2O, and one with methanol in the crystal lattice, fac-[RhCl3(Me3P)3]·0.5CH3OH. These rhodium compounds exhibit distorted octahedral coordination spheres at the metal and are isotypic with the analogous iridium compounds previously reported by us [Merola et al. (2013 ▶). Polyhedron, 54, 67-73]. Comparison is made between the rhodium and iridium compounds, highlighting their isostructural relationships.

Crystal structure of chlorido-(η(2)-phenyl iso-thio-cyanate-κ(2) C,S)-mer-tris-(tri-methyl-phosphane-κP)iridium(I).

The molecule of the title compound, [IrCl(C7H5NS)(C3H9P)3], is a distorted octa-hedral iridium complex with three PMe3 ligands arranged in a meridional geometry, a chloride ion cis to all three PMe3 groups and the phenyl iso-thio-cyanate ligand bonded in an η(2)-fashion through the C and S atoms. The C atom is trans to the chloride ion and the S atom is responsible for a significant deviation from an ideal octa-hedral geometry. The geometric parameters for the metal-complexing phenyl isothiocyanate group are compared with other metal-complexed phenyl iso-thio-cyanates, as well as with examples of uncomplexed aryl iso-thio-cyanates.

Hydrido(prolinato-κ(2) N,O)tris-(tri-methyl-phosphane-κP)iridium(III) hexa-fluorido-phosphate.

The title complex, [Ir(C5H8NO2)H(C3H9P)3]PF6, has two independent anion-cation pairs in the asymmetric unit. The geometry about each Ir(III) atom is pseudo-octa-hedral with a meridional arrangement of the P(CH3)3 ligands, N,O-bidentate coordination of prolinate and a hydride ligand trans to the prolinate N atom. The independent Ir(III) moieties are joined by N-H⋯O hydrogen bonds and the N-H⋯O bonding motif continues throughout the structure, creating an extended chain parallel to the c-axis direction. The methyl groups of one P(CH3)3 ligand are rotationally disordered over two sets of sites in a 0.62 (2):0.38 (2) ratio.

N (1),N (2)-Di-methyl-ethane-1,2-diaminium dichloride.

The cation of the title salt, C4H14N2 (2+)·2Cl(-), is located on a crystallographic inversion center and is bis-ected by a mirror plane, with one quarter of the C4H14N2 (2+)·2Cl(-) formula unit being crystallographically unique. he chloride ions also sit on a mirror plane. The conformation of the cation is a regular straight-chain conformation with all non-H atoms in anti positions. In the crystal, hydrogen bonding between N-H groups and chloride anions yields a zigzag ladder-type structure along [010].

Tri-methyl-phospho-nium trans-tetra-chlorido-bis-(tri-methyl-phosphane-κP)iridate(III).

The title compound, [HP(CH3)3][IrCl4{(H3C)3P}2], consists of a tri-methyl-phospho-nium cation and a tetra-chlorido-bis-(tri-methyl-phosphane)iridate(III) anion. The anion has an octa-hedral arrangement of ligands, with the tri-methyl-phosphane groups occupying trans positions. The Ir(III) atom sits on an inversion center with one P(CH3)3 ligand and two chloride ligands in the asymmetric unit. The tri-methyl-phospho-nium cation is disordered about a twofold rotation axis. The title compound is the first structurally characterized tetra-chlorido-bis-(phosphane)iridate complex.

mer-Hydridotris(tri-methyl-phosphane-κP)(d-valinato-κ(2) N,O)iridium hexa-fluorido-phosphate di-chloro-methane 0.675-solvate.

The title compound, [Ir(C5H10NO2)H(C3H9P)3]PF6·0.675CH2Cl2, an iridium compound with a meridional arrangement of PMe3 groups, O,N-bidentate coordination of d-valine and with a hydride ligand trans to the N atom is compared with the l-valine complex reported previously. As expected, the complexes from the corresponding l and d isomers of valine crystallize in enanti-omorphic space groups (P43 and P41, respectively). In the crystal, N-H⋯O and N-H⋯F hydrogen bonding is observed, the N-H to carbonyl oxygen hydrogen bond producing a helical motif that proceeds along the 41 screw of the c axis.

Bis-(η(2)-ethyl-ene)(η(5)-inden-yl)iridium(I).

The asymmetric unit of the title compound, [Ir(C9H7)(C2H4)2], consists of two independent mol-ecules. The bonding between iridium and the five-membered ring of the indenyl ligand shows the usual asymmetry associated with the typical ring slippage responsible for the enhanced activity of indenyl metal compounds when compared with the analogous cyclo-penta-dienyl metal compound. There are three short Ir-C bonds of 2.210 (3), 2.190 (4) and 2.220 (3) Šand two long Ir-C bonds to the C atoms that are part of the fused six-membered ring of 2.349 (4) and 2.366 (3) Šfor one of the independent mol-ecules [2.208 (4), 2.222 (3), 2.197 (4) Šfor the short distances and 2.371 (3) and 2.358 (3) Šfor the long distances in the second mol-ecule]. This results in both indenyl ligands being slightly kinked, with dihedral angles of 6.8 (4)° and 6.5 (4)°.

Aqua-bis-(4-methyl-benzene-sulfonato-κO)(η(5)-penta-methyl-cyclo-penta-dien-yl)rhodium(III) monohydrate.

The title half-sandwich rhodium(III) complex, [Rh(C10H15)(C7H7O3S)2(H2O)]·H2O, consists of a π-bonded penta-methyl-cyclo-penta-dienyl group, two σ-bonded tosyl-ate groups and an aqua ligand. The structure displays both inter- and intra-molecular O-H⋯O hydrogen bonding. The inter-molecular hydrogen bonding results in an extended helical chain along a 21 screw axis parallel to c, due to hydrogen bonding from the coordinating water ligand to the lattice water mol-ecule and then to a sulfonate O atom of a different asymmetric unit.

(S)-α-Benzyl-prolinium cis-[(S)-α-benzyl-prolinato]dichloridopalladium(II).

The title complex salt, (C12H16NO2)[PdCl2(C12H14NO2)], is of inter-est with respect to organic and organometallic catalysis. The compound crystallizes as very small orange-red irregular prisms and the asymmetric unit contains three crystallographically distinct cation-anion pairs. The coordination geometry about the palladium atoms is square-planar with the chloride ligands cis to one another. The structure displays N-H⋯Cl and O-H⋯O hydrogen bonding such that the N-H⋯Cl hydrogen bonds align the cation-anion pairs in a linear fashion along [001], with the O-H⋯O hydrogen bonds connecting these linear strands along [100] and [010].

Transition metal-α-amino acid complexes with antibiotic activity against Mycobacterium spp.

Synthetic iridium-, rhodium-, and ruthenium-amino acid complexes with hydrophobic l-amino acids have antibiotic activity against Mycobacterium spp., including Mycobacterium bovis BCG and the rapidly growing species Mycobacterium abscessus and Mycobacterium chelonae. Concentrations of transition metal-amino acid complexes demonstrating hemolysis or cytotoxicity were 10- to 25-fold higher than were the MICs.