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π‐Hole Interactions Involving Nitro Aromatic Ligands in Protein Structures
- Source :
- Chemistry-A European Journal, 25(58), 13436-13443. Wiley-VCH Verlag, Chemistry (Weinheim an Der Bergstrasse, Germany)
- Publication Year :
- 2019
- Publisher :
- Wiley, 2019.
-
Abstract
- Studying noncanonical intermolecular interactions between a ligand and a protein constitutes an emerging research field. Identifying synthetically accessible molecular fragments that can engage in intermolecular interactions is a key objective in this area. Here, it is shown that so‐called “π‐hole interactions” are present between the nitro moiety in nitro aromatic ligands and lone pairs within protein structures (water and protein carbonyls and sulfurs). Ample structural evidence was found in a PDB analysis and computations reveal interaction energies of about −5 kcal mol−1 for ligand–protein π‐hole interactions. Several examples are highlighted for which a π‐hole interaction is implicated in the superior binding affinity or inhibition of a nitro aromatic ligand versus a similar non‐nitro analogue. The discovery that π‐hole interactions with nitro aromatics are significant within protein structures parallels the finding that halogen bonds are biologically relevant. This has implications for the interpretation of ligand–protein complexation phenomena, for example, involving the more than 50 approved drugs that contain a nitro aromatic moiety.<br />Nitro aromatic ligands have a positive electrostatic potential on the nitro group N atom (the so‐called π‐hole) that can interact with lone‐pair O/S electrons with energies of about −5 kcal mol−1. A thorough Protein Data Bank (PDB) analysis and scrutiny of relevant literature revealed the structural and functional significance of π–hole interactions of nitro aromatic ligands within proteins.
- Subjects :
- Models, Molecular
Stereochemistry
Protein Data Bank (RCSB PDB)
Plasma protein binding
Ligands
010402 general chemistry
01 natural sciences
Catalysis
Structure-Activity Relationship
Protein structure
pi–hole interactions
Moiety
Computer Simulation
Amino Acid Sequence
Databases, Protein
Lone pair
nitro compounds
Full Paper
Molecular Structure
010405 organic chemistry
Chemistry
Organic Chemistry
Intermolecular force
Proteins
Water
Hydrogen Bonding
General Chemistry
Full Papers
Ligand–Protein Interactions
Ligand (biochemistry)
0104 chemical sciences
PDB analysis
density functional calculations
Nitro
Thermodynamics
Hydrophobic and Hydrophilic Interactions
Protein Binding
Subjects
Details
- ISSN :
- 15213765 and 09476539
- Volume :
- 25
- Database :
- OpenAIRE
- Journal :
- Chemistry – A European Journal
- Accession number :
- edsair.doi.dedup.....ca2596ba2a2eb8b69e3b2665356d5239