Understanding ligand properties is essential for computational high-throughput screening of transition metal complexes. However, ligand properties such as net charge and other information such as thei Show more
Understanding ligand properties is essential for computational high-throughput screening of transition metal complexes. However, ligand properties such as net charge and other information such as their application area are often absent or inconsistently recorded in crystallographic datasets. Here, we construct a ligand dataset from 126,985 mononuclear transition metal complexes curated from the Cambridge Structural Database. Using an iterative charge-balancing workflow that combines complex charges, metal oxidation states, and consensus across crystallographic observations, we confidently assign net charges to 66,810 ligands among 94,581 identified unique ligand structures to curate the Boston Open-Shell Ligand (BOS-Lig) dataset. The workflow assigns ligand charges in homoleptic complexes first and then iteratively propagates these assignments across heteroleptic environments, allowing charges to be inferred even when direct charge information is unavailable. We analyze cases where simple heuristics such as the octet rule would have failed and introduce a purity metric to identify when our charge assignments may be incorrect. Each ligand is also classified in terms of its metal coordinating atoms and whether there are multiple variants (i.e., hemilability). We then link complexes to their associated journal abstracts and apply a topic-modeling workflow to link 25,146 ligands with functional application areas spanning reactivity, redox chemistry, biological chemistry, and photophysical chemistry. Together, we provide an experimentally grounded dataset of ligand chemical space that connects charge and functional application as a foundation for computational screening and data-driven ligand design. Show less
G-quadruplexes turned out to be important targets for the development of novel targeted
anticancer/antiviral therapies. More than 3000 G-quadruplex small-molecule ligands have been
described, with mos Show more
G-quadruplexes turned out to be important targets for the development of novel targeted
anticancer/antiviral therapies. More than 3000 G-quadruplex small-molecule ligands have been
described, with most of them exerting anticancer/antiviral activity by inducing telomeric damage
and/or altering oncogene or viral gene expression in cancer cells and viruses, respectively. For
some ligands, in-depth NMR and/or crystallographic studies were performed, providing detailed
knowledge on their interactions with diverse G-quadruplex targets. Here, the PDB-deposited NMR
and crystal structures of the complexes between telomeric, oncogenic or viral G-quadruplexes and
small-molecule ligands, of both organic and metal-organic nature, have been summarized and
described based on the G-quadruplex target, from telomeric DNA and RNA G-quadruplexes to DNA
oncogenic G-quadruplexes, and finally to RNA viral G-quadruplexes. An overview of the structural
details of these complexes is here provided to guide the design of novel ligands targeting more
efficiently and selectively cancer- and virus-related G-quadruplex structures.
Platella, C.; Montesarchio, D. Insights
into the Small Molecule Targeting of Show less