scholarly journals Control of Dynamic sp3-C Stereochemistry

2021 ◽  
Author(s):  
Aisha Bismillah ◽  
Toby Johnson ◽  
Burhan Hussein ◽  
Andrew Turley ◽  
Ho Chi Wong ◽  
...  
Keyword(s):  
Ligand Exchange ◽  
Dynamic Properties ◽  
Building Blocks ◽  
Metal Coordination ◽  
Chiral Molecules ◽  
Conformational Isomerism ◽  
Configurational Change ◽  
Nitrogen Inversion ◽  
Intermolecular Reactions ◽  
Cope Rearrangements

Abstract Stereogenic sp3-hybridized carbon centres are fundamental building blocks of chiral molecules. Unlike dynamic stereogenic motifs, such as sp3-nitrogen centres or atropisomeric biaryls, sp3-carbon centres are usually fixed, requiring intermolecular reactions to undergo configurational change. Here, we report the internal enantiomerization of fluxional carbon cages and the consequences of their adaptive configurations for the transmission of stereochemical information. The sp3-carbon stereochemistry of the rigid tricyclic cages is inverted through strain-assisted Cope rearrangements, emulating the low-barrier configurational dynamics typical for sp3 nitrogen inversion or conformational isomerism. This dynamic enantiomerization can be stopped, restarted, or slowed by external reagents, while the configuration of the cage is controlled by neighbouring, fixed stereogenic centres. As part of a phosphoramidite–olefin ligand, the fluxional cage acts as a conduit to transmit stereochemical information from the ligand while also transferring its dynamic properties to chiral-at-metal coordination environments, influencing catalysis and ligand exchange energetics.

Hierarchy of Supramolecular Arrangements and Building Blocks: Inverted Paradigm of Crystal Engineering in the Unprecedented Metal Coordination of Methylene Blue

2017 ◽  
Vol 56 (6) ◽  
pp. 3512-3516 ◽  
Author(s):  
Stefano Canossa ◽  
Alessia Bacchi ◽  
Claudia Graiff ◽  
Paolo Pelagatti ◽  
Giovanni Predieri ◽  
...  
Keyword(s):  
Methylene Blue ◽  
Crystal Engineering ◽  
Building Blocks ◽  
Metal Coordination ◽  
Supramolecular Arrangements

scholarly journals Diverse protein assembly driven by metal and chelating amino acids with selectivity and tunability

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Minwoo Yang ◽  
Woon Ju Song
Keyword(s):  
Amino Acids ◽  
Self Assembly ◽  
Protein Structures ◽  
Functional Materials ◽  
Building Blocks ◽  
Unnatural Amino Acid ◽  
Metal Coordination ◽  
Specific Chemical ◽  
Natural Building ◽  
Kinetics Of

AbstractProteins are versatile natural building blocks with highly complex and multifunctional architectures, and self-assembled protein structures have been created by the introduction of covalent, noncovalent, or metal-coordination bonding. Here, we report the robust, selective, and reversible metal coordination properties of unnatural chelating amino acids as the sufficient and dominant driving force for diverse protein self-assembly. Bipyridine-alanine is genetically incorporated into a D3 homohexamer. Depending on the position of the unnatural amino acid, 1-directional, crystalline and noncrystalline 2-directional, combinatory, and hierarchical architectures are effectively created upon the addition of metal ions. The length and shape of the structures is tunable by altering conditions related to thermodynamics and kinetics of metal-coordination and subsequent reactions. The crystalline 1-directional and 2-directional biomaterials retain their native enzymatic activities with increased thermal stability, suggesting that introducing chelating ligands provides a specific chemical basis to synthesize diverse protein-based functional materials while retaining their native structures and functions.

Tetra- and Octalactam Macrocycles and Catenanes with Exocyclic Metal Coordination Sites: Versatile Building Blocks for Supramolecular Chemistry

2003 ◽  
Vol 9 (6) ◽  
pp. 1332-1347 ◽  
Author(s):  
Xi-you Li ◽  
Jens Illigen ◽  
Martin Nieger ◽  
Steffen Michel ◽  
Christoph A. Schalley
Keyword(s):  
Supramolecular Chemistry ◽  
Building Blocks ◽  
Metal Coordination ◽  
Coordination Sites

Flexible “piperazine–pyrazine” building blocks: conformational isomerism of “equatorial–axial” sites toward the constructions of silver(i) coordination chains

CrystEngComm ◽  
2010 ◽  
Vol 12 (11) ◽  
pp. 3388 ◽  
Author(s):  
Shu-Chun Hsu ◽  
Jing-Yun Wu ◽  
Chin-Fen Lee ◽  
Chung-Chou Lee ◽  
Long-Li Lai ◽  
...  
Keyword(s):  
Building Blocks ◽  
Conformational Isomerism

scholarly journals The Generated Databases (GDBs) as a Source of 3D-shaped Building Blocks for Use in Medicinal Chemistry and Drug Discovery

2020 ◽  
Vol 74 (4) ◽  
pp. 241-246 ◽  
Author(s):  
Kris Meier ◽  
Sven Bühlmann ◽  
Josep Arús-Pous ◽  
Jean-Louis Reymond
Keyword(s):  
Drug Discovery ◽  
Medicinal Chemistry ◽  
Organic Molecules ◽  
Chemical Space ◽  
Building Blocks ◽  
Chiral Molecules ◽  
Hydrogen Atoms ◽  
Quaternary Centers ◽  
Medical Needs ◽  
Unmet Medical Needs

Drug discovery is in constant need of new molecules to develop drugs addressing unmet medical needs. To assess the chemical space available for drug design, our group investigates the generated databases (GDBs) listing all possible organic molecules up to a defined size, the largest of which is GDB-17 featuring 166.4 billion molecules up to 17 non-hydrogen atoms. While known drugs and bioactive compounds are mostly aromatic and planar, the GDBs contain a plethora of non-aromatic 3D-shaped molecules, which are very useful for drug discovery since they generally have more desirable absorption, distribution, metabolism, excretion and toxicity (ADMET) properties. Here we review GDB enumeration methods and the selection and synthesis of GDB molecules as modulators of ion channels. We summarize the constitution of GDB subsets focusing on fragments (FDB17), medicinal chemistry (GDBMedChem) and ChEMBL-like molecules (GDBChEMBL), and the ring system database GDB4c as a rich source of novel 3D-shaped chiral molecules containing quaternary centers, such as the recently reported trinorbornane.

Sign in / Sign up

Export Citation Format

Share Document