Lisinopril chemical structure
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Lisinopril Chemical Structure: Key Features and Description
Lisinopril is a synthetic drug classified as an angiotensin-converting enzyme (ACE) inhibitor, widely used for treating hypertension and heart failure. Chemically, lisinopril is a lysine derivative of enalaprilat and is structurally similar to its substrate, but it notably lacks the sulfhydryl group found in captopril 17. Its chemical name is (S)-1-[N2-(1-carboxy-3-phenylpropyl)-L-lysyl]-L-proline dihydrate, and its empirical formula is C21H31N3O5·2H2O 17.
Molecular Structure and Functional Groups
Lisinopril contains several important functional groups:
- Two carboxylate groups
- A primary amino group
- A secondary amine
- A proline ring
- A phenylpropyl side chain
The molecule is ampholytic and tetraprotic, meaning it can both donate and accept protons at multiple sites. The carboxylate on the proline ring is more basic than the carboxylate in the side chain, which affects its acid-base behavior and pharmacokinetic properties .
Crystallographic and Solid-State Structure
Single-crystal X-ray studies have revealed that lisinopril dihydrate exists in a double zwitterionic form in the solid state, meaning it has both positive and negative charges within the same molecule . The crystal structure has been precisely determined, showing the arrangement of atoms and the presence of water molecules in the dihydrate form 35. Lisinopril can also form anhydrous and amorphous solid forms, which have different dissolution rates compared to the dihydrate .
Coordination and Binding Properties
Lisinopril acts as a monodentate ligand, typically binding to metal ions through one of its carboxylate oxygen atoms 246. In complexes with zinc, the coordination can involve both oxygen and nitrogen atoms, depending on the conditions, and can lead to the formation of one-dimensional coordination polymers . These binding properties are important for its biological activity and interactions with enzymes and metal ions.
Interaction with Angiotensin-Converting Enzyme (ACE)
The structure of lisinopril bound to human ACE has been resolved at high resolution, showing that lisinopril fits into the active site of the enzyme and interacts with key amino acid residues and the zinc ion at the catalytic center . This structural insight explains its effectiveness as an ACE inhibitor and provides a basis for designing new inhibitors with improved selectivity and pharmacological profiles .
Conclusion
Lisinopril’s chemical structure is defined by its lysine-derived backbone, multiple ionizable groups, and zwitterionic nature in the solid state. Its ability to form complexes with metal ions and its precise fit within the ACE active site are central to its pharmacological action. The detailed understanding of its structure, both in isolation and in complex with ACE, has been crucial for its development and clinical use 1356789.
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