Chlorhexidine
[CAS# 55-56-1]

Identification

• Classification: API >> Synthetic anti-infective drugs >> Disinfectant antiseptic
• Name: Chlorhexidine
• Synonyms: Bis(5-(p-chlorophenyl)biguanidinio)hexane; Hexamethylenebis(5-(4-chlorophenyl)biguanide); N,N'-Bis(4-chlorophenyl)-3,12-diimino-tetraazatetradecanediimidamide
• Molecular Formula: C₂₂H₃₀Cl₂N₁₀
• Molecular Weight: 505.45
• CAS Registry Number: 55-56-1
• EC Number: 200-238-7
• SMILES: C1=CC(=CC=C1N/C(=N/C(=NCCCCCCN=C(/N=C(/NC2=CC=C(C=C2)Cl)\N)N)N)/N)Cl

Properties

• Melting point: 134-136 ºC (Expl.)
• Solubility: water: soluble 0.08% (20 ºC) (Expl.)

Safety Data

• Hazard Symbols: GHS05;GHS07;GHS08;GHS09 Danger
• Hazard Statements: H302-H315-H318-H319-H334-H335-H373-H400-H410
• Precautionary Statements: P233-P260-P261-P264-P264+P265-P270-P271-P273-P280-P284-P301+P317-P302+P352-P304+P340-P305+P351+P338-P305+P354+P338-P317-P319-P321-P330-P332+P317-P337+P317-P342+P316-P362+P364-P391-P403-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Chronic hazardous to the aquatic environment	Aquatic Chronic	1	H410
Acute hazardous to the aquatic environment	Aquatic Acute	1	H400
Eye irritation	Eye Irrit.	2	H319
Skin irritation	Skin Irrit.	2	H315
Serious eye damage	Eye Dam.	1	H318
Respiratory sensitization	Resp. Sens.	1	H334
Specific target organ toxicity - single exposure	STOT SE	3	H335
Specific target organ toxicity - repeated exposure	STOT RE	2	H373
Acute toxicity	Acute Tox.	4	H302
Chronic hazardous to the aquatic environment	Aquatic Chronic	2	H411
Skin sensitization	Skin Sens.	1	H317

• Transport Information: UN 3077

Discovory and Applicatios

Chlorhexidine is a widely used antiseptic and disinfectant belonging to the class of biguanide compounds. Chemically, it is known as 1,1'-hexamethylenebis\[5-(4-chlorophenyl)biguanide], with the molecular formula C₂₂H₃₀Cl₂N₁₀. Chlorhexidine was first synthesized in the 1950s and introduced into medical practice due to its broad-spectrum antimicrobial activity and relative safety for topical use.

The discovery of chlorhexidine was motivated by the search for effective antiseptics that could combat a wide range of bacteria, fungi, and some viruses. It demonstrated strong bactericidal and bacteriostatic properties by disrupting microbial cell membranes and precipitating cellular contents, leading to cell death. Chlorhexidine’s mechanism involves binding to negatively charged bacterial cell walls and increasing permeability, causing leakage of intracellular components.

Clinically, chlorhexidine is used in various formulations including solutions, gels, mouthwashes, and impregnated dressings. It is commonly applied for skin disinfection before surgery, oral hygiene to reduce dental plaque and gingivitis, wound care, and sterilization of surgical instruments. Its use in dentistry is widespread due to its efficacy in controlling oral biofilms and reducing dental caries and periodontal disease.

Chlorhexidine exhibits activity against Gram-positive and Gram-negative bacteria, yeasts such as Candida species, and some enveloped viruses. However, it has limited effect against bacterial spores and certain non-enveloped viruses. The compound’s antimicrobial spectrum and substantivity—the ability to adhere to surfaces and release slowly—make it valuable for prolonged antiseptic action.

Pharmacokinetically, chlorhexidine is poorly absorbed through intact skin or mucous membranes, minimizing systemic exposure during topical application. However, ingestion or parenteral use is contraindicated due to potential toxicity. Local adverse effects may include skin irritation, allergic reactions, and staining of teeth and oral mucosa with prolonged use in mouthwash formulations.

Resistance to chlorhexidine is relatively uncommon but has been reported, often involving changes in bacterial cell membrane composition or efflux pump activity. Its broad use has prompted studies on appropriate concentrations and exposure times to reduce the risk of resistance development.

Analytical techniques for chlorhexidine include ultraviolet-visible (UV-Vis) spectrophotometry, high-performance liquid chromatography (HPLC), and mass spectrometry (MS), which allow quantification in pharmaceutical products and biological samples. These methods ensure quality control and support pharmacokinetic and safety evaluations.

In summary, chlorhexidine is a synthetic biguanide antiseptic with broad antimicrobial activity used extensively in medical and dental fields. Its mechanism of disrupting microbial membranes underlies its effectiveness, and its versatile formulations enable applications ranging from skin disinfection to oral hygiene. The compound remains an essential antiseptic due to its efficacy, safety, and prolonged action on treated surfaces.

References

1987. The effect on early plaque formation, gingivitis and salivary bacterial counts of mouthwashes containing hexetidine/zinc, aminefluoride/tin or chlorhexidine. Journal of Clinical Periodontology, 14(8).
DOI: 10.1111/j.1600-051x.1987.tb00992.x

1987. Periodic subgingival antimicrobial irrigation of periodontal pockets. II. Microbiological and radiographical observations. Journal of Clinical Periodontology, 14(9).
DOI: 10.1111/j.1600-051x.1987.tb00997.x

1987. Prolonged oral reduction of Streptococcus mutans in humans after chlorhexidine disinfection followed by fluoride treatment. Scandinavian journal of dental research, 95(4).
DOI: 10.1111/j.1600-0722.1987.tb01847.x