Making the InChI FAIR and sustainable while moving to inorganics.

The InChI (International Chemical Identifier) standard stands as a cornerstone in chemical informatics, facilitating the structure-based identification and exchange chemical information about compounds across various platforms and databases. The InChI as a unique canonical line notation has made chemical structures searchable on the internet at a broad scale. The largest repositories working with InChIs contain more than 1 billion structures.

Tuning The Intracellular Distribution of [3+2+1] Iridium(III) Complexes In Bacterial And Mammalian Cells By iClick Reaction With Biomolecular Carriers Functionalized With Alkynone Groups.

Three iridium(III) triazolato complexes of the general formula [Ir(triazolato)(ppy)(terpy)]PF with ppy=2-phenylpyridine and terpy=2,2':6',2''-terpyridine were efficiently prepared by iClick reaction of [Ir(N)(ppy)(terpy)]PF, with alkynes and alkynones, which allowed facile introduction of biological carriers such as biotin and cholic acid. In contrast to the precursor azido complex, which decomposed upon photoexcitation on a very short time scale, the triazolato complexes were stable in solution for up to 48 h. They emit in the spectral region around 540 nm with a quantum yield of 15-35 % in aerated acetonitrile solution and exhibit low cytotoxicity with IC values >50 μM for most complexes in L929 and HeLa cells, demonstrating their high suitability as luminescent probes.

Antibacterial activity of Au(I), Pt(II), and Ir(III) biotin conjugates prepared by the iClick reaction: influence of the metal coordination sphere on the biological activity.

A series of biotin-functionalized transition metal complexes was prepared by iClick reaction from the corresponding azido complexes with a novel alkyne-functionalized biotin derivative ([Au(triazolato)(PPh)], [Pt(dpb)(triazolato)], [Pt(triazolato)(terpy)]PF, and [Ir(ppy)(triazolato)(terpy)]PF with dpb = 1,3-di(2-pyridyl)benzene, ppy = 2-phenylpyridine, and terpy = 2,2':6',2''-terpyridine and R = CH, R' = biotin). The complexes were compared to reference compounds lacking the biotin moiety. The binding affinity toward avidin and streptavidin was evaluated with the HABA assay as well as isothermal titration calorimetry (ITC).

Isostructural Series of Ni(II), Pd(II), Pt(II), and Au(III) Azido Complexes with a N^C^N Pincer Ligand to Elucidate Trends in the iClick Reaction Kinetics and Structural Parameters of the Triazolato Products.

An isoelectronic and isostructural series of cyclometalated azido complexes [M(N)(dpb)] with M = Ni(II), Pd(II), Pt(II), and Au(III) based on the N^C^N pincer ligand 1,3-di(2-pyridyl)phenide (dpb) was characterized by X-ray diffraction analysis and investigated for reactivity in the iClick reaction with a wide range of internal and terminal alkynes by using H and F NMR spectroscopy. Reaction rate constants were found to increase with greater charge density in the order Ni(II) > Pd(II) > Pt(II) > Au(III). Terminal alkynes R-C≡C-R' with strongly electron-withdrawing groups R and R' exhibited faster kinetics than those with electron-donating substituents in the order CF > ketone > ester > H > phenyl ≫ amide, while R = CH resulted in complete loss of reactivity.

Taming the Biological Activity of Pd(II) and Pt(II) Complexes with Triazolato "Protective" Groups: H, Se Nuclear Magnetic Resonance and X-ray Crystallographic Model Studies with Selenocysteine to Elucidate Differential Thioredoxin Reductase Inhibition.

The biological activity of Pd(II) and Pt(II) complexes toward three different cancer cell lines as well as inhibition of selenoenzyme thioredoxin reductase (TrxR) was modulated in an unexpected way by the introduction of triazolate as a "protective group" to the inner metal coordination sphere using the iClick reaction of [M(N)(terpy)]PF [M = Pd(II) or Pt(II) and terpy = 2,2':6',2″-terpyridine] with an electron-poor alkyne. In a cell proliferation assay using A549, HT-29, and MDA-MB-231 human cancer cell lines, the palladium compound was significantly more potent than the isostructural platinum analogue and exhibited submicromolar activity on the most responsive cell line. This difference was also reflected in the inhibitory efficiency toward TrxR with IC values of 0.

The manganese carbonyl complex [Mn(CO)(tqa-κN)]Br: A novel antimicrobial agent with the potential to treat avian pathogenic Escherichia coli (APEC) infections.

The development of alternatives to antibiotics is essential for the treatment of animal infections and as a measure to reduce the selective pressure on antibiotics that are critical for human medicine. Metal complexes have been highlighted for their antimicrobial activity against several bacterial pathogens. In particular, manganese carbonyl complexes have shown efficacy against multidrug-resistant Gram-negative pathogens, and relatively low cytotoxicity against avian macrophages and in wax moth larval models.

Ferrocenoyl-substituted quinolinone and coumarin as organometallic inhibitors of SARS-CoV-2 3CLpro main protease.

The 3-chymotrypsin-like protease 3CLpro from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a potential target for antiviral drug development. In this work, three organometallic ferrocene-modified quinolinones and coumarins were compared to their benzoic acid ester analogues with regard to inhibition of 3CLpro using an HPLC-based assay with a 15mer model peptide as the substrate. In contrast to FRET-based assays, this allows direct identification of interference of buffer constituents with the inhibitors, as demonstrated by the complete abolishment of ebselen inhibitory activity in the presence of dithiothreitol as a redox protectant.

Electrospray Mass Spectrometry to Study Combinatorial iClick Reactions and Multiplexed Kinetics of [Ru(N)(N∧N)(terpy)]PF with Alkynes of Different Steric and Electronic Demand.

In a combinatorial approach, a family of ruthenium(II) azido complexes [Ru(N)(N∧N)(terpy)]PF with terpy = 2,2':6',2″-terpyridine and N∧N as a bidentate chelator derived from 2,2'-biypridine and its 4,4'-disubstituted derivatives, 2,2'-bipyrimidine, and 1,10-phenanthroline were reacted with different internal and terminal alkynes to give access to a total of 7 × 7 = 49 triazolato complexes in a room-temperature catalyst-free iClick reaction. The reactants were mixed in a repurposed high-performance liquid chromatography (HPLC) autosampler, and the reaction progress was monitored by direct injection into an electrospray mass spectrometer. The ratio of the peak intensities of [Ru(N)(N∧N)(terpy)] and [Ru(triazolato)(N∧N)(terpy)] was converted to a colored heat map for facile visual inspection of the conversion ratio.

Tuning the coordination properties of chiral pseudopeptide bis(2-picolyl)amine and iminodiacetamide ligands in Zn(II) and Cu(II) complexes.

Seven bis(2-picolyl)amine (bpa) and five iminodiacetamide (imda) ligands were prepared with different modifications in their side chain structure. The coordination properties of the ligands (L) were influenced by changes in the aliphatic linker length (C1, C2, or C3), amide group isomers and type of chiral terminal group. Complexation with Cu(II) afforded two polymorphs of a ML complex which features tetradentate coordination of a ligand with C2 linkers, while crystal structures of three - ML complexes with Cu(II) and Ni(II) show tridentate coordination of ligands with a C3 linker.

SELFIES and the future of molecular string representations.

Artificial intelligence (AI) and machine learning (ML) are expanding in popularity for broad applications to challenging tasks in chemistry and materials science. Examples include the prediction of properties, the discovery of new reaction pathways, or the design of new molecules. The machine needs to read and write fluently in a chemical language for each of these tasks.

TUCAN: A molecular identifier and descriptor applicable to the whole periodic table from hydrogen to oganesson.

TUCAN is a canonical serialization format that is independent of domain-specific concepts of structure and bonding. The atomic number is the only chemical feature that is used to derive the TUCAN format. Other than that, the format is solely based on the molecular topology.

Metallodrug Profiling against SARS-CoV-2 Target Proteins Identifies Highly Potent Inhibitors of the S/ACE2 interaction and the Papain-like Protease PL.

The global spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has called for an urgent need for dedicated antiviral therapeutics. Metal complexes are commonly underrepresented in compound libraries that are used for screening in drug discovery campaigns, however, there is growing evidence for their role in medicinal chemistry. Based on previous results, we have selected more than 100 structurally diverse metal complexes for profiling as inhibitors of two relevant SARS-CoV-2 replication mechanisms, namely the interaction of the spike (S) protein with the ACE2 receptor and the papain-like protease PL .

Ultrafast photochemistry of a molybdenum carbonyl-nitrosyl complex with a triazacyclononane coligand.

Transition metal complexes capable of releasing small molecules such as carbon monoxide and nitric oxide upon photoactivation are versatile tools in various fields of chemistry and biology. In this work, we report on the ultrafast photochemistry of [Mo(CO)(NO)(Prtacn)]PF (Prtacn = 1,4,7-triisopropyl-1,4,7-triazacyclononane), which was characterized under continuous illumination and with femtosecond UV-pump/UV-probe and UV-pump/MIR-probe spectroscopy, as well as with stationary calculations. The experimental and theoretical results demonstrate that while the photodissociation of one of the two CO ligands upon UV excitation can be inferred both on an ultrafast timescale as well as under exposure times of several minutes, no evidence of NO release is observed under the same conditions.

Antibacterial activity of Mn(I) and Re(I) tricarbonyl complexes conjugated to a bile acid carrier molecule.

A bifunctional cholic acid-bis(2-pyridylmethyl)amine (bpa) ligand featuring an amide linker was coordinated to a manganese(i) or rhenium(i) tricarbonyl moiety to give [M(bpacholamide)(CO)3] with M = Mn, Re in good yield and very high purity. Strong antibacterial activity was observed against four strains of methicillin-susceptible (MSSA) and methicillin-resistant (MRSA) Staphylococcus aureus, with minimum inhibitory concentrations (MICs) in the range of 2-3.5 μM.

Manganese complex [Mn(CO)(tpa-κN)]Br increases antibiotic sensitivity in multidrug resistant Streptococcus pneumoniae.

Objectives: The emergence of multidrug-resistance (MDR) in Streptococcus pneumoniae clones and non-vaccine serotypes necessitate the development of novel treatment strategies. This work aimed to determine the efficacy of the Mn complex [Mn(CO)(tpa-κN)]Br against clinically important MDR strains of S. pneumoniae.

Biological activity of manganese(i) tricarbonyl complexes on multidrug-resistant Gram-negative bacteria: From functional studies to in vivo activity in Galleria mellonella.

Three new manganese(i) tricarbonyl complexes [Mn(bpqa-κ3N)(CO)3]Br, [Mn(bqpa-κ3N)(CO)3]Br, and [Mn(CO)3(tqa-κ3N)]Br as well as the previously described compound [Mn(CO)3(tpa-κ3N)]Br with bpqa = bis(2-pyridinylmethyl)(2-quinolinylmethyl)amine, bqpa = bis(2-quinolinylmethyl)(2-pyridinylmethyl)amine, tqa = tris(2-quinolinylmethyl)amine, and tpa = tris(2-pyridinylmethyl)amine were examined for their antibacterial activities on 14 different multidrug-resistant clinical isolates of Acinetobacter baumannii and Pseudomonas aeruginosa, in recognition of the current antimicrobial resistance (AMR) concerns with these pathogens. Minimal inhibitory concentrations (MIC) of the most potent tqa compound were in the mid-micromolar range and generally lower than that of the free ligand. Activity against both bacterial species increased with the number of quinolinylmethyl groups and lipophilicity in the order of tpa < bpqa < bqpa ≈ tqa, consistent with measured increases in release of ATP, a uniquely cytoplasmic biomolecule and induced permeability to exogenous fluorescent intercalating compounds.

iClick Reactions of Square-Planar Palladium(II) and Platinum(II) Azido Complexes with Electron-Poor Alkynes: Metal-Dependent Preference for N1 vs N2 Triazolate Coordination and Kinetic Studies with H and F NMR Spectroscopy.

Two square-planar palladium(II) and platinum(II) azido complexes [M(N)(L)] with L = phenyl-2-[1-(2-pyridinyl)ethylidene]hydrazine carbothioamide reacted with four different electron-poor alkynes R-C≡C-R' with R = R' = COOCH, COOEt, COOCHCHOCH or R = CF, R' = COOEt in a [3 + 2] cycloaddition "iClick" reaction. The resulting triazolate complexes [M(triazolate)(L)] were isolated by simple precipitation and/or washing in high purity and good yield. Six out of the eight new compounds feature the triazolate ligand coordinated to the metal center via the N2 nitrogen atom, but fortuitous solubility properties allowed isolation of the N1 isomer in two cases from acetone.

2,2':6',2''-Terpyridine switches from tridentate to monodentate coordination in a gold(iii) terpy complex upon reaction with sodium azide.

Reaction of [AuCl(terpy-κ-N)]Cl with an excess of sodium azide did not result in the expected exchange of the chlorido by an azido ligand to give [Au(N)(terpy-κ-N)]. Instead, X-ray structure analysis showed that the isolated product is [Au(N)(terpy-κ-N)], in which the terpyridine ligand is in a very rare monodentate coordination mode. This is also the dominant species in solution, together with a minor amount of [Au(N)(terpy-κ-N)].

Metallointercalators and Metalloinsertors: Structural Requirements for DNA Recognition and Anticancer Activity.

As the carrier of the inheritable information in cells, DNA has been the target of metal complexes for over 40 years. In this chapter, the focus will be on non-covalent recognition of the highly structured DNA surface by substitutionally inert metal complexes capable of either sliding in between the normal base pairs as metallointercalators or flipping out thermodynamically destabilized mispaired nucleobases as metalloinsertors. While most of the compounds discussed are based on ruthenium(II) and rhodium(III) due to their stable octahedral coordination environment and low-spin 4d6 electronic configuration, most recent developments of alternative metal complexes, based on both transition metals and main group elements, will also be highlighted.

Antimicrobial activity of carbon monoxide-releasing molecule [Mn(CO)3(tpa-κ3N)]Br versus multidrug-resistant isolates of Avian Pathogenic Escherichia coli and its synergy with colistin.

Antimicrobial resistance is a growing global concern in human and veterinary medicine, with an ever-increasing void in the arsenal of clinicians. Novel classes of compounds including carbon monoxoide-releasing molecules (CORMs), for example the light-activated metal complex [Mn(CO)3(tpa-κ3N)]Br, could be used as alternatives/to supplement traditional antibacterials. Avian pathogenic Escherichia coli (APEC) represent a large reservoir of antibiotic resistance and can cause serious clinical disease in poultry, with potential as zoonotic pathogens, due to shared serotypes and virulence factors with human pathogenic E.

A manganese photosensitive tricarbonyl molecule [Mn(CO)3(tpa-κN)]Br enhances antibiotic efficacy in a multi-drug-resistant Escherichia coli.

Carbon monoxide-releasing molecules (CORMs) are a promising class of new antimicrobials, with multiple modes of action that are distinct from those of standard antibiotics. The relentless increase in antimicrobial resistance, exacerbated by a lack of new antibiotics, necessitates a better understanding of how such novel agents act and might be used synergistically with established antibiotics. This work aimed to understand the mechanism(s) underlying synergy between a manganese-based photoactivated carbon monoxide-releasing molecule (PhotoCORM), [Mn(CO)3(tpa-κN)]Br [tpa=tris(2-pyridylmethyl)amine], and various classes of antibiotics in their activities towards Escherichia coli EC958, a multi-drug-resistant uropathogen.

Catalyst-free room-temperature iClick reaction of molybdenum(ii) and tungsten(ii) azide complexes with electron-poor alkynes: structural preferences and kinetic studies.

Two isostructural and isoelectronic group VI azide complexes of the general formula [M(η-allyl)(N)(bpy)(CO)] with M = Mo, W and bpy = 2,2'-bipyridine were prepared and fully characterized, including X-ray structure analysis. Both reacted smoothly with electron-poor alkynes such as dimethyl acetylenedicarboxylate (DMAD) and 4,4,4-trifluoro-2-butynoic acid ethyl ester in a catalyst-free room-temperature iClick [3 + 2] cycloaddition reaction. Reaction with phenyl(trifluoromethyl)acetylene, on the other hand, did not lead to any product formation.

Antimicrobial Activity of the Manganese Photoactivated Carbon Monoxide-Releasing Molecule [Mn(CO)3(tpa-κ(3)N)](+) Against a Pathogenic Escherichia coli that Causes Urinary Infections.

Aims: We set out to investigate the antibacterial activity of a new Mn-based photoactivated carbon monoxide-releasing molecule (PhotoCORM, [Mn(CO)3(tpa-κ(3)N)](+)) against an antibiotic-resistant uropathogenic strain (EC958) of Escherichia coli.

Results: Activated PhotoCORM inhibits growth and decreases viability of E. coli EC958, but non-illuminated carbon monoxide-releasing molecule (CORM) is without effect.

Amino acid bioconjugation via iClick reaction of an oxanorbornadiene-masked alkyne with a Mn(I)(bpy)(CO)3-coordinated azide.

The catalyst-free room temperature iClick reaction of an unsymmetrically 2,3-disubstituted oxanorbornadiene (OND) as a "masked" alkyne equivalent with [Mn(N3)(bpy(CH3,CH3))(CO)3] leads to isolation of a phenylalanine ester bioconjugate, in which the model amino acid is linked to the metal moiety via a N-2-coordinated triazolate formed in a cycloaddition-retro-Diels-Alder (crDA) reaction sequence, in a novel approach to bioorthogonal coupling reactions based on metal-centered reactivity.

Introducing [Mn(CO)3(tpa-κ(3)N)](+) as a novel photoactivatable CO-releasing molecule with well-defined iCORM intermediates - synthesis, spectroscopy, and antibacterial activity.

[Mn(CO)3(tpa-κ(3)N)]Br was prepared as a novel photoactivatable CO-releasing molecule (PhotoCORM) from [MnBr(CO)5] and tris(2-pyridylmethyl)amine (tpa) for the delivery of carbon monoxide to biological systems, with the κ(3)N binding mode of the tetradentate tpa ligand demonstrated by X-ray crystallography. The title compound is a CORM prodrug stable in solution in the dark for up to 16 h. However, photoactivation at 365 nm leads to CO release from the metal coordination sphere and transfer to haem proteins, as demonstrated by the standard myoglobin assay.