What is the Difference Between Ligand and Substrate

The main difference between ligand and substrate is that a ligand is a molecule or ion that forms a complex with a central metal atom or ion by donating one or more pairs of electrons, whereas a substrate is a molecule upon which an enzyme acts.

Ligands and substrates are fundamental concepts in the field of chemistry, playing crucial roles in various chemical and biological processes.

Key Areas Covered

1. What is a Ligand  
      – Definition, Features, Classification
2. What is a Substrate
      – Definition, Features, Types
3. Similarities Between Ligand and Substrate
      – Outline of Common Features
4. Difference Between Ligand and Substrate
      – Comparison of Key Differences
5. FAQ: Ligand and Substrate
      – Frequently Asked Questions

Key Terms

Ligand, Substrate

Difference Between Ligand and Substrate - Comparison Summary

What is a Ligand

A ligand is a molecule or ion capable of donating one or more pairs of electrons to a central metal atom or ion. This act of electron donation results in the formation of a coordination complex, where the metal and ligands are bound together through coordinate covalent bonds. The formation of these complexes gives rise to distinctive properties and behaviors that set coordination compounds apart from other chemical entities. Ligands exhibit remarkable diversity in their structures and electron-donating capabilities.

Classification of Ligands 

Ligands can be broadly classified based on the number of electron pairs they donate and their charge:

Monodentate Ligands: Monodentate ligands donate a single pair of electrons to the metal center. Common examples include ammonia (NH₃), water (H₂O), and chloride ions (Cl⁻).

Bidentate Ligands: Bidentate ligands donate two pairs of electrons to the metal center. Ethylenediamine (en) and oxalate ion (C₂O₄²⁻) are examples of bidentate ligands.

Polydentate Ligands: Polydentate ligands can donate more than two pairs of electrons. Ethylenediaminetetraacetate (EDTA) is a well-known polydentate ligand.

Heterocyclic Ligands: Ligands that contain atoms other than carbon in their rings, such as nitrogen or oxygen, are termed heterocyclic ligands. Pyridine is a common example.

Ambidentate Ligands: Ambidentate ligands are capable of binding through two different atoms. For instance, nitrite ions (NO₂⁻) can coordinate through either nitrogen or oxygen.

Chelating Ligands: Chelating ligands are a subclass of polydentate ligands that form a ring structure with the central metal ion.

Compare Ligand and Substrate

Figure 1: Cobalt Complex with Five Ligands

The coordination number of a metal ion in a complex is determined by the number of ligands attached to it. Ligands influence the geometry of the coordination complex, dictating whether it adopts a linear, square planar, tetrahedral, octahedral, or other geometries.

For example, in an octahedral complex, a metal ion is coordinated to six ligands. If the ligands are all identical, the complex may exhibit perfect octahedral symmetry. However, the presence of different ligands can lead to a distorted octahedral geometry.

Ligands find extensive applications in various industrial processes and medicinal chemistry. In catalysis, certain ligands enhance the reactivity of metal catalysts. In medicinal chemistry, ligands are essential components of many drugs, influencing the bioavailability and binding interactions of the drug with its target.

What is a Substrate

A substrate is a molecule upon which an enzyme acts, serving as the reactant in a biochemical reaction. Enzymes, as catalysts, facilitate and accelerate these reactions, and the specificity of their action is intimately tied to the nature and structure of the substrate.

The interaction between enzymes and substrates is highly specific, resembling a lock-and-key or induced-fit model. The active site of an enzyme, a region with a precisely complementary structure to the substrate, recognizes and binds to the substrate, facilitating the catalytic conversion of the substrate into products.

The binding of a substrate to the active site of an enzyme involves various non-covalent interactions, including hydrogen bonding, van der Waals forces, and electrostatic interactions. These interactions are crucial for stabilizing the enzyme-substrate complex and facilitating the catalytic process.

The specificity of these interactions ensures that enzymes typically recognize and act on a particular substrate or a group of structurally related substrates. This exquisite specificity is central to the selectivity and efficiency of enzymatic reactions in living organisms.

Ligand vs Substrate

Figure 2: Enzyme Substrate Complex

Common Types of Substrates

Substrates in biological systems encompass a vast array of molecules, reflecting the diversity of biochemical processes. Some common types of substrates include:

Small Molecules: Simple compounds like glucose, amino acids, and fatty acids often serve as substrates for enzymes involved in metabolism.

Nucleic Acids: DNA and RNA act as substrates for enzymes involved in processes such as DNA replication, transcription, and translation.

Complex Molecules: Larger molecules, such as proteins, can also be substrates for specific enzymes. Proteases, for instance, catalyze the hydrolysis of peptide bonds in proteins.

Multiple Substrates: Enzymes often work on multiple substrates simultaneously, orchestrating complex reactions. An example is the enzyme DNA polymerase, which uses nucleotide substrates to synthesize DNA.

Role of Substrates

The role of substrates in enzymatic reactions is foundational to the biochemical processes that sustain life. From the digestion of food to the synthesis of biomolecules, substrates are the molecular protagonists that enable enzymes to carry out their catalytic functions.

In cellular respiration, for instance, glucose serves as a substrate for enzymes involved in glycolysis, ultimately yielding energy in the form of ATP. In DNA replication, nucleotide substrates are used by DNA polymerase to synthesize new DNA strands.

Understanding substrate-enzyme interactions has profound implications in medicine and biotechnology. Drug development often targets specific enzymes involved in disease processes, aiming to modulate substrate-enzyme interactions for therapeutic purposes. In biotechnology, enzymatic reactions are harnessed for various applications, from the production of biofuels to the synthesis of pharmaceuticals.

Similarities Between Ligand and Substrate

  • Ligands and substrates both have the potential to form complexes with other molecules.
  • Furthermore, both exhibit specificity in their interactions. Ligands show specificity for certain metal ions, and substrates are specific to the active sites of particular enzymes.
  • Both can be involved in catalytic processes.

Difference Between Ligand and Substrate


Ligands are molecules or ions that can donate one or more pairs of electrons to a central metal atom or ion, forming a coordination complex, whereas substrates are molecules upon which enzymes act.


Ligands participate in the formation of coordination complexes with metal ions, while substrates are the reactants in enzymatic reactions.


Moreover, ligands interact with metal ions through the donation of electron pairs, forming coordinate covalent bonds, while substrates interact with enzymes through non-covalent interactions, such as hydrogen bonding, van der Waals forces, and electrostatic interactions.

FAQ: Ligand and Substrate

What are the examples of substrates?

Glucose, sucrose, and starch are some examples of substrates.

What are the examples of ligands?

Examples of ligands include ammonia (NH₃), water (H₂O), chloride ions (Cl⁻), and ethylenediamine (en).

What are the types of ligands?

Anionic ligands, cationic ligands, and neutral ligands are the three types of ligands.


Ligands are molecules or ions that form complexes with central metal atoms, influencing their properties and reactivity. On the other hand, substrates are the molecules upon which enzymes act, undergoing chemical transformations during catalysis. Thus, this is the main difference between ligand and substrate.


1. “Ligands.” Byju’s.
2. “Substrate.” Byju’s.

Image Courtesy:

1. “HCo(CO)4-3D-balls” (Public Domain) via Commons Wikimedia
2. “Enzyme-substrate complex” By Original: OpenStax CollegeDerivative: Khan Academy – KhanAcademy.org (Derived from Figure 2, Open Stax College, Biology) (CC BY 4.0) via Commons Wikimedia

About the Author: Hasini A

Hasini is a graduate of Applied Science with a strong background in forestry, environmental science, chemistry, and management science. She is an amateur photographer with a keen interest in exploring the wonders of nature and science.

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