Orotic acid, also known as pyrimidinecarboxylic acid, is an organic compound that plays a key role in nucleotide biosynthesis. Chemically categorized as a heterocyclic carboxylic acid, orotic acid possesses distinct structural and physicochemical characteristics that contribute to its biological activity and relevance in metabolic pathways. Understanding its chemical properties is essential for its study in biochemistry, pharmaceuticals, and metabolic research.
Molecular Structure and Formula
The molecular formula of orotic acid is C₅H₄N₂O₄, and its IUPAC name is 2,6-dioxo-1,2,3,6-tetrahydropyrimidine-4-carboxylic acid. It features a six-membered pyrimidine ring with two ketone groups at the 2 and 6 positions and a carboxyl group attached at the 4 position.
Molecular weight: 156.10 g/mol
Structure: A planar aromatic heterocycle
Functional groups: Two ketone groups (=O), one carboxylic acid (-COOH), and two nitrogen atoms within the ring
These features give orotic acid its distinct chemical reactivity and solubility characteristics.
Acid-Base Properties
Orotic acid behaves as a weak acid due to the presence of the carboxyl group. It has two main acidic protons:
The carboxyl group (–COOH)
A proton on the pyrimidine ring (due to tautomerism and resonance within the ring)
The pKa of the carboxyl group is around 3.1, indicating it donates a proton in mildly acidic conditions. Its relatively low acidity allows orotic acid to participate in acid-base reactions and form salts, such as sodium orotate, which are more water-soluble and commonly used in supplementation or research.
Solubility and Stability
Orotic acid is:
Sparingly soluble in cold water, but solubility increases with heat or when converted into a salt (e.g., sodium orotate)
Insoluble in most organic solvents, such as ether or chloroform
Stable under normal storage conditions, but may decompose under strong acidic or basic conditions, or at elevated temperatures
The low solubility in water contributes to its tendency to accumulate when metabolic disorders occur, such as in orotic aciduria.
Tautomerism and Resonance
Orotic acid exhibits tautomerism, particularly involving the keto-enol form within the pyrimidine ring. The major tautomer at physiological pH is the diketo form, with carbonyl groups at positions 2 and 6. Resonance stabilization across the ring structure enhances its chemical stability and influences its ability to interact with enzymes and other biomolecules in the nucleotide synthesis pathway.
Coordination and Salt Formation
Orotic acid readily forms salts with metal ions, such as sodium, potassium, and calcium. These salts are often more soluble and are used in research or dietary supplements. The molecule can also act as a ligand, coordinating metal ions through its carboxyl and carbonyl oxygen atoms, a property explored in bioinorganic and pharmaceutical chemistry.
Spectral Properties
UV absorption: Orotic acid absorbs ultraviolet light, with a peak around 280 nm, due to its conjugated ring system. This property is useful for analytical detection and quantification using UV spectroscopy.
NMR: The proton and carbon nuclear magnetic resonance (NMR) spectra of orotic acid reveal characteristic chemical shifts for the carboxylic proton, ring protons, and carbonyl carbons, aiding in structural identification and purity analysis.
Reactivity
While orotic acid is relatively stable, it can undergo:
Esterification reactions with alcohols under acidic conditions (targeting the carboxylic group)
Amidation to form orotates and derivatives
Condensation reactions as part of biochemical pathways
Its reactivity is largely defined by its acidic functional groups and conjugated ring system.
Conclusion
Orotic acid possesses a unique set of chemical properties characterized by its heterocyclic ring structure, weak acidity, and ability to form salts and coordinate metals. These properties make it biologically functional as an intermediate in pyrimidine biosynthesis and chemically versatile for use in research and industry. A thorough understanding of its chemical behavior supports its applications in biochemistry, diagnostics, and pharmaceutical development.
