The syntheses and the characterization by chemical analysis, (1)H and (31)P NMR spectroscopy, and mass spectrometry of a series of linear triphenylphosphine gold(I) complexes with substituted N-heterocycle ligands (L), [(PPh3)Au(I)(L)](+), is reported. The reaction of [(PPh3)Au(L)](+) (L = Cl(-) or substituted N- heterocyclic pyridine) with the C-terminal (Cys3His) finger of HIVNCp7 shows evidence by mass spectrometry (ESI-MS) and (31)P NMR spectroscopy of a long-lived {(PPh3)Au}-S-peptide species resulting from displacement of the chloride or pyridine ligand by zinc-bound cysteine with concomitant displacement of Zn(2+). In contrast, reactions with the Cys2His2 finger-3 of the Sp1 transcription factor shows significantly reduced intensities of {(PPh3)Au} adducts. The results suggest the possibility of systematic (electronic, steric) variations of "carrier" group PR3 and "leaving" group L as well as the nature of the zinc finger in modulation of biological activity. The cytotoxicity, cell cycle signaling effects, and cellular accumulation of the series are also reported. All compounds display cytotoxicity in the micromolar range upon 96 h continuous exposure to human tumor cells. The results may have relevance for the reported inhibition of viral load in simian virus by the gold(I) drug auranofin.

In light of the Covid-19 outbreak, this review brings the historical and current literature efforts towards the development of antiviral metallodrugs. Classical compounds such as CTC-96 and auranofin are discussed...

In this review we compare and discuss results of compounds already reported as anticancer agents based on isatin-derivatives, metalated as well as non-metallated. Isatin compounds can be obtained from plants, marine animals, and is also found in human fluids as a metabolite of amino acids. Its derivatives include imines, hydrazones, thiosemicarbazones, among others, already focused on numerous anticancer studies. Some of them have entered in pre-clinical and clinical tests as antiangiogenic compounds or inhibitors of crucial proteins. As free ligands or coordinated to metal ions, such isatin derivatives showed promising antiproliferative properties against different cancer cells, targeting different biomolecules or organelles. Binding to metal ions usually improves its biological properties, indicating a modulation by the metal and by the ligand in a synergistic process. They also reveal diverse mechanisms of action, being able of binding DNA, generating reactive species that cause oxidative damage, and inhibiting selected proteins. Strategies used to improve the efficiency and selectivity of these compounds comprise structural modification of the ligands, metalation with different ions, syntheses of mononuclear and dinuclear species, and use of inserted or anchored compounds in selected drug delivery systems.

Reaction of the Au-C N chelate [Au(bnpy)Cl ] with the full-length zinc finger (ZnF; ZnCys His) of HIV nucleocapsid protein NCp7 results in C-S aryl transfer from the Au organometallic species to a cysteine of the ZnF. The reaction is general and occurs even for finger 3 of the transcription factor Sp1, containing a ZnCys His coordination sphere. This reaction is the first demonstration of group transfer from a coordination compound to biologically important zinc fingers, and is especially noteworthy for the ZnCys His transcription factors. The work expands the corpus of organometallic species which can efficiently modify biomolecules through C-atom transfer. The electronic features of the gold compound leading to this unexpected reaction were explored by X-ray absorption spectroscopy.

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Traveling wave ion mobility (TWIM) mass spectrometry (MS) is a powerful method for the structural and conformational analysis of proteins and peptides, enabling the differentiation of isomeric peptides (or proteins) that have the same sequence but are modified at different residues. In this study, the TWIM-MS technique was used to separate isomeric Au metallopeptide ions that were formed by Zn displacement from the parent zinc fingers (ZFs). The synthetic gold finger peptides were derived from the C-terminus of the HIV nucleocapsid p7 protein (NCp7-F2) and finger 3 of the Sp1 transcription factor (Sp1-F3). TWIM-MS enabled the acquisition of distinct product ion spectra for each isomer, clearly indicating the binding sites for the major conformers in the presence of multiple coordination possibilities. Collision cross-section measurements showed that the aurated peptide has a slightly more compact structure than the parent zinc compound NCp7-F2, which showed only one conformation.

Traveling wave ion mobility (TWIM) mass spectrometry (MS) is a powerful method for the structural and conformational analysis of proteins and peptides, enabling the differentiation of isomeric peptides (or proteins) that have the same sequence but are modified at different residues. In this study, the TWIM‐MS technique was used to separate isomeric AuI metallopeptide ions that were formed by ZnII displacement from the parent zinc fingers (ZFs). The synthetic gold finger peptides were derived from the C‐terminus of the HIV nucleocapsid p7 protein (NCp7‐F2) and finger 3 of the Sp1 transcription factor (Sp1‐F3). TWIM‐MS enabled the acquisition of distinct product ion spectra for each isomer, clearly indicating the binding sites for the major conformers in the presence of multiple coordination possibilities. Collision cross‐section measurements showed that the aurated peptide has a slightly more compact structure than the parent zinc compound NCp7‐F2, which showed only one conformation.

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