Approximate Length

~ 12 minutes

Learning Outcomes

• Differentiate between ionic and covalent bonds. 
• Assign the appropriate charges to functional groups in molecules at biological pH (~7.4). 
• Explain the defining features of each type of chemical bond/interactions. Discuss which of these types are common and uncommon in protein-ligand binding and why. 
• Use the periodic table to predict electronegativity trends of atoms. 
• Recognize donors and acceptors in hydrogen bonds. 
• Identify factors that affect the strength of hydrogen bonds and compare the relative strengths of different hydrogen bonds. 

Key Words

Covalent bond: The bond between two atoms sharing one or more pairs of electrons. 

Ionic bond: Electrostatic attraction between oppositely charged species. 

Hydrogen bond: A dipole-dipole interaction occurring between a hydrogen covalently bound to an N, O, or F atom (donor) and another N, O, or F atom (acceptor). 

Electronegativity: The ability of an atom to attract electrons to itself in a bond. 

Dipole: A concentration of positive electric charge separated from a concentration of negative charge, often due to differences in the electronegativity of atoms. 

van der Waals interactions: Weak, short-range, electrostatic, attractive forces between uncharged molecules arising from dipole moments. If atoms get too close, the van der Waals force becomes repulsive. 

Van der Waals radius: An imaginary hard sphere representing the distance of closest approach for another atom (the closest two atoms can get without repelling each other).

Summary

• Covalent bonds are the strongest and longest-lasting interaction but are rare in protein-ligand binding because we want the interaction to be reversible. 
• Ionic bonds are electrostatic interactions between a negatively charged species and a positively charged species. 
• Oxygen atoms are often part of negatively charged functional groups, such as a deprotonated carboxylic acid. 
• Amines and other nitrogen-containing compounds are common positively charged functional groups. 
• Hydrogen bonds are a common receptor-ligand interaction occurring between a donor and a receptor: 
• Donors need to have a hydrogen covalently bound to an electronegative atom.  
• Acceptors need to have a lone pair of electrons to interact with the donated hydrogen. 
•  The strength of a hydrogen bond depends on 
• the electronegativity of the covalently bound atom,  
• the distance between the donor and acceptor, and  
• their geometry (180 degrees is preferred). 
• A dipole is when a concentration of positive electric charge is separated from negative charge.

Module Outline

• Pretest 
• Covent bond 
• Ionic bonds 
• Commonly charged species in Biochemistry  
• Quiz: Recognizing charges on functional groups and ionic versus molecular 
• Hydrogen bonding (donors and acceptors) 
• Electronegativity and practice 
• Dipoles 
• Strength as a function of distance and orientation with practice 
• van der Waal interactions 
• Steric repulsion 
• Summary and quiz

Important Visuals