Identification

Name
Propiolactone
Accession Number
DB09348
Type
Small Molecule
Groups
Approved, Withdrawn
Description

Propiolactone is a lactone compound with a four-membered ring. It is a colorless liquid with a pungent slightly sweet odor. Propiolactone is a disinfectant used for the sterilization of blood plasma, vaccines, tissue grafts, surgical instruments, and enzymes. It has been used against bacteria, fungi, and virus.[1] It is currently FDA approved for its use as an indirect additive used in food contact substances. Propiolactone was first commercially available in the United States in 1958.[1]

Structure
Thumb
Synonyms
  • 1,3-propiolactone
  • 3-propanolide
  • beta-Propiolactone
  • betapron
  • Propiolactona
  • Propiolactone
  • β-propiolactone
External IDs
NSC-21626
Categories
UNII
6RC3ZT4HB0
CAS number
57-57-8
Weight
Average: 72.063
Monoisotopic: 72.021129369
Chemical Formula
C3H4O2
InChI Key
VEZXCJBBBCKRPI-UHFFFAOYSA-N
InChI
InChI=1S/C3H4O2/c4-3-1-2-5-3/h1-2H2
IUPAC Name
oxetan-2-one
SMILES
O=C1CCO1

Pharmacology

Indication

Propiolactone was used for vaccines, tissue grafts, surgical instruments, and enzymes, as a sterilant of blood plasma, water, milk and nutrient broth as a vapor-phase disinfectant in enclosed spaces. Its sporicidal action is used against vegetative bacteria, pathologic fungi, and viruses.[5] It is no longer used in medical procedures or in food.[1]

Pharmacodynamics

When employed under conditions of maximum effectiveness, propiolactone is approximately 25 more active as a vapor phase disinfectant than formaldehyde, 4000 times more active than ethylene oxide and 50000 times more active than methyl bromide.[6] It has been shown to be mutagenic by inducing cell transformation, chromosomal aberrations and chromatoid exchange. Propiolactone has been shown to be mutagenic in both somatic and germ cells.[7]

Mechanism of action

Propiolactone is an alkylating agent that acts through alkylation of carboxyl- and hydroxyl- groups. The lactone ring splits either at the first or third carbon.[6] Propiolactone reacts with polynucleotides and DNA, mainly at N7 of guanine and N1 of adenine to form carboxyethyl derivatives. It also forms adducts with N3 of cytosine and thymine.[7]

TargetActionsOrganism
ADNA
adduct
Humans
Absorption
Not Available
Volume of distribution
Not Available
Protein binding

Propiolactone is highly bound to proteins showing an almost 2-fold binding increase when compared to DNA and RNA.[4]

Metabolism

Propiolactone is completely hydrolyzed after 3 hours of being in an aqueous solution and this time can be even faster in the presence of cellular debris and cell culture media.[8] When in water, the lactone ring opens at the alkyl and acyl bonds.[3] The degradation products of propiolactone are not toxic.[8]

Route of elimination
Not Available
Half life

The half-life of propiolactone in water is of 225 minutes.[2]

Clearance
Not Available
Toxicity

Based on experimental trials, it has been determined that propiolactone is a human carcinogen. The results have shown the generation of tumors in several tissues and from different administration routes.[1]

Affected organisms
  • Humans and other mammals
  • Fungi
  • Bacteria
  • Various viruses
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
  1. Authors unspecified: betaPropiolactone. Rep Carcinog. 2011;12:366-7. [PubMed:21863089]
  2. Uittenbogaard JP, Zomer B, Hoogerhout P, Metz B: Reactions of beta-propiolactone with nucleobase analogues, nucleosides, and peptides: implications for the inactivation of viruses. J Biol Chem. 2011 Oct 21;286(42):36198-214. doi: 10.1074/jbc.M111.279232. Epub 2011 Aug 25. [PubMed:21868382]
  3. LOGRIPPO GA: Investigations of the use of beta-propiolactone in virus inactivation. Ann N Y Acad Sci. 1960 Jan 13;83:578-94. [PubMed:14417982]
  4. Colburn NH, Boutwell RK: The in vivo binding of beta-propiolactone to mouse skin DNA, RNA, and protein. Cancer Res. 1968 Apr;28(4):642-52. [PubMed:5649055]
  5. EPA report [Link]
  6. Himedialabs [Link]
  7. Monograph propiolactone [Link]
  8. Science alert [Link]
External Links
KEGG Drug
D05630
KEGG Compound
C19297
PubChem Compound
2365
PubChem Substance
310265222
ChemSpider
2275
ChEBI
49073
ChEMBL
CHEMBL1200627
Wikipedia
Beta-Propiolactone
MSDS
Download (49.6 KB)

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Liquid
Experimental Properties
PropertyValueSource
melting point (°C)-33.4ºCRep Carcinog. 2011; 12:366-7
boiling point (°C)Decomposes (155ºC)'MSDS'
water solubility370 g/L at 25ºCRep Carcinog. 2011; 12:366-7
logP-0.564EPA
Predicted Properties
PropertyValueSource
Water Solubility436.0 mg/mLALOGPS
logP-0.55ALOGPS
logP-0.14ChemAxon
logS0.78ALOGPS
pKa (Strongest Basic)-7.1ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area26.3 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity15.55 m3·mol-1ChemAxon
Polarizability6.55 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as beta propiolactones. These are organic compounds containing a four-member lactone (a cyclic ester).
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Lactones
Sub Class
Beta propiolactones
Direct Parent
Beta propiolactones
Alternative Parents
Oxetanes / Carboxylic acid esters / Oxacyclic compounds / Monocarboxylic acids and derivatives / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds
Substituents
Beta_propiolactone / Oxetane / Carboxylic acid ester / Oxacycle / Monocarboxylic acid or derivatives / Carboxylic acid derivative / Organic oxygen compound / Organic oxide / Hydrocarbon derivative / Organooxygen compound
Molecular Framework
Aliphatic heteromonocyclic compounds
External Descriptors
propan-3-olide (CHEBI:49073)

Targets

1. DNA
Kind
Nucleotide
Organism
Humans
Pharmacological action
Yes
Actions
Adduct
General Function:
Used for biological information storage.
Specific Function:
DNA contains the instructions needed for an organism to develop, survive and reproduce.
Molecular Weight:
2.15 x 1012 Da
References
  1. Himedialabs [Link]
  2. Monograph propiolactone [Link]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Binder
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. Mate U, Solomon JJ, Segal A: In vitro binding of beta-propiolactone to calf thymus DNA and mouse liver DNA to form 1-(2-carboxyethyl) adenine. Chem Biol Interact. 1977 Sep;18(3):327-36. [PubMed:912815]

Drug created on November 27, 2015 15:14 / Updated on December 16, 2018 06:57