Nanostructured Molecular Systems and Materials (MSMn) Group, Departamento de Química Orgánica, Facultad de Ciencias, Universidad Autónoma de Madrid, 28049, Madrid, Spain.
Published: June 2020
AI Article Synopsis
Article Abstract
In analogy to covalent reactions, the understanding of noncovalent association pathways is fundamental to influence and control any supramolecular process. Following an approach that is reminiscent of covalent methodologies, we study here, for the first time, the mechanism of G-quadruplex formation in organic solvents. Our results support a reaction pathway in which the cation shifts the equilibrium towards a G-quartet transient intermediate, which then acts as a template in the formation of the G-quadruplex product.
Kirsten rat sarcoma (KRAS) is a frequently mutated oncogene responsible for several oncogenic KRAS variants and for driving tumor proliferation. Some nonsmall cell lung cancer (NSCLC) tumors exhibit KRAS G12C mutations, which can be targeted for inhibition using covalent and more recently noncovalent inhibitors. Sotorasib was the first FDA-approved G12C inhibitor that has shown efficacy in lung cancer patients, but with mixed responses.
Understanding molecular motifs that can interfere with amyloid fibrillation through non-covalent interactions is essential for addressing abnormal protein aggregation and associated human diseases. The pursuit of efficient diagnostic and treatment approaches for Alzheimer's disease (AD) has resulted in the development of M8HQ, a multifaceted small molecule turn-on probe derived from 8-hydroxyquinoline with versatile capabilities. M8HQ shows a strong affinity for amyloid beta (Aβ) fibrils, and its ability to target lysosomes enhances therapeutic precision by localizing within these organelles.
In this study, we introduce two datasets for nanoscale noncovalent binding, featuring complexes at the hundred-atom scale, benchmarked using coupled cluster with single, double, and perturbative triple [CCSD(T)] excitations extrapolated to the complete basis set (CBS) limit. The first dataset, L14, comprises 14 complexes with canonical CCSD(T)/CBS benchmarks, extending the applicability of CCSD(T)/CBS binding benchmarks to systems as large as 113 atoms. The second dataset, vL11, consists of 11 even larger complexes, evaluated using the local CCSD(T)/CBS method with stringent thresholds, covering systems up to 174 atoms.
* The study evaluated interaction energy through comparisons with spectroscopic data, geometric properties, and other factors to uncover correlations, particularly focusing on the C═O stretching frequency and nuclear magnetic resonance changes.
* While the interaction energy can be estimated from experimental measurements, standard AIM measurements correlate less effectively, and the σ-hole depth on the Lewis acid does not strongly relate to bond strength due to the limitations of electrostatic metrics.
POCOP-Ni(II) pincer compounds, initially studied for their catalytic properties, were evaluated for their anticancer and antioxidant activities in this research.
Four specific POCOP-Ni(II) complexes derived from phloroglucinol showed significant cytotoxicity against various cancer cell lines, with IC values between 2.43 and 7.85 μM.
The study also employed techniques like single-crystal X-ray diffraction to analyze molecular structures and suggested that these complexes can intercalate with DNA, indicating potential mechanisms for their therapeutic effects.
