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Hydrogen Bonds01:04

Hydrogen Bonds

9.0K
A hydrogen bond is formed when a weakly positive hydrogen atom already bonded to one electronegative atom (for example, the oxygen in the water molecule) is attracted to another electronegative atom from another polar molecule, such as water (H2O), hydrogen fluoride (HF), or ammonia (NH3). The huge electronegativity difference between the H atom (2.1) and the atom to which it is bonded (4.0 for an F atom, 3.5 for an O atom, or 3.0 for an N atom), combined with the very small size of an H atom...
9.0K
Drug-Receptor Bonds01:25

Drug-Receptor Bonds

3.1K
Drug-receptor bonds are formed through various chemical forces when drugs interact with target cells. Covalent bonds, strong and irreversible, are exemplified by DNA-alkylating anticancer agents that inhibit cell division. However, such irreversible drug binding lacks selectivity and can modify the DNA of the surrounding healthy cells. Covalent binding often contributes to tissue toxicity, as seen with chloroform and paracetamol metabolites binding to the liver, causing hepatotoxicity.
In...
3.1K
Ligand Binding Sites02:40

Ligand Binding Sites

13.0K
Proteins are dynamic macromolecules that carry out a wide variety of essential processes; however, the activities of most proteins depend on their interactions with other molecules or ions, known as ligands.
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
13.0K
Noncovalent Attractions in Biomolecules02:35

Noncovalent Attractions in Biomolecules

52.4K
Noncovalent attractions are associations within and between molecules that influence the shape and structural stability of complexes. These interactions differ from covalent bonding in that they do not involve sharing of electrons.
Four types of noncovalent interactions are hydrogen bonds, van der Waals forces, ionic bonds, and hydrophobic interactions.
Hydrogen bonding results from the electrostatic attraction of a hydrogen atom covalently bonded to a strong-electronegative atom like oxygen,...
52.4K
Metal-Ligand Bonds02:51

Metal-Ligand Bonds

21.4K
The hemoglobin in the blood, the chlorophyll in green plants, vitamin B-12, and the catalyst used in the manufacture of polyethylene all contain coordination compounds. Ions of the metals, especially the transition metals, are likely to form complexes.
In these complexes, transition metals form coordinate covalent bonds, a kind of Lewis acid-base interaction in which both of the electrons in the bond are contributed by a donor (Lewis base) to an electron acceptor (Lewis acid). The Lewis acid in...
21.4K
Introduction to Chemical Bonds01:01

Introduction to Chemical Bonds

8.4K
Chemical Bonds
The electrons of the outermost energy level determine the energetic stability of the atom and its tendency to form chemical bonds with other atoms. The innermost electron shell has a maximum capacity of two electrons, but the next two electron shells can each have a maximum of eight electrons. This is known as the octet rule, which states that, with the exception of the innermost shell, atoms are most stable energetically when they have eight electrons in their valence shell, the...
8.4K

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Related Experiment Video

Updated: Aug 24, 2025

Incorporating Target Protein Structure Flexibility and Dynamics in Computational Drug Discovery Using Ensemble-Based Docking Analysis
08:49

Incorporating Target Protein Structure Flexibility and Dynamics in Computational Drug Discovery Using Ensemble-Based Docking Analysis

Published on: June 20, 2025

466

Hydrogen-Bond Donors in Drug Design.

Peter W Kenny1

  • 1Berwick-on-Sea, North Coast Road, Blanchisseuse, Saint George, Trinidad and Tobago.

Journal of Medicinal Chemistry
|October 25, 2022
PubMed
Summary

Drug design faces challenges with hydrogen-bond donors, unlike acceptors. Understanding their interactions is key for optimizing drug properties like solubility and target binding.

Area of Science:

  • Medicinal Chemistry
  • Drug Design
  • Computational Chemistry

Background:

  • Hydrogen-bond donors present unique challenges in drug design compared to acceptors.
  • Drug-like molecules typically have more hydrogen-bond acceptors, leading to polarity imbalances.
  • This imbalance impacts crucial drug properties such as permeability and aqueous solubility.

Purpose of the Study:

  • To discuss the implications of polarity imbalance caused by hydrogen-bond donors and acceptors.
  • To explore design opportunities arising from frustrated solvation and secondary electrostatic interactions.
  • To compare different types of hydrogen-bond donors and their equivalents in drug design.

Main Methods:

  • Analysis of polarity distribution in drug-like compounds.

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Construction and Systematical Symmetric Studies of a Series of Supramolecular Clusters with Binary or Ternary Ammonium Triphenylacetates
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Construction and Systematical Symmetric Studies of a Series of Supramolecular Clusters with Binary or Ternary Ammonium Triphenylacetates

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Covalent Fragment Screening Using the Quantitative Irreversible Tethering Assay
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Covalent Fragment Screening Using the Quantitative Irreversible Tethering Assay

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Construction and Systematical Symmetric Studies of a Series of Supramolecular Clusters with Binary or Ternary Ammonium Triphenylacetates
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  • Discussion of solvation effects related to hydrogen-bonding.
  • Comparative analysis of oxygen, nitrogen, and carbon-based hydrogen-bond donors.
  • Exploration of halogen- and chalcogen-bond donors as alternatives.
  • Main Results:

    • Hydrogen-bond donors pose greater design challenges than acceptors due to polarity imbalances.
    • The presence of a hydrogen-bond donor often correlates with an acceptor, but not vice versa.
    • Aligned donors and acceptors lead to frustrated solvation and secondary electrostatic interactions, offering design opportunities.

    Conclusions:

    • Optimizing drug permeability and solubility requires careful consideration of hydrogen-bond donor/acceptor balance.
    • Exploiting frustrated solvation and electrostatic interactions can enhance ligand recognition.
    • Novel hydrogen-bond donor equivalents like halogen- and chalcogen-bonds offer new design strategies.