Paromomycin (41-19-9) Physical and Chemical Properties
Paromomycin
A naturally derived aminoglycoside antibiotic used as an active pharmaceutical ingredient (commonly supplied as a sulfate salt) for clinical formulations and research applications.
| CAS Number | 41-19-9 |
| Family | Aminoglycosides |
| Typical Form | Powder or crystalline solid |
| Common Grades | EP |
Paromomycin is an aminoglycoside antibiotic belonging to the amino cyclitol glycoside structural class. Structurally it couples a 4,6-diamino-2,3-dihydroxycyclohexane (streptamine-like) core to a disaccharide motif containing multiple amino‑deoxy sugar residues; the empirical composition is \(\ce{C23H45N5O14}\). The molecule contains numerous primary and secondary amino groups and an extensive network of hydroxyls, producing very high polarity, a large topological polar surface area, and dense hydrogen‑bonding capacity. Electronically the basic sites are predominantly aliphatic amines that are protonated under physiological and mildly acidic conditions, rendering the molecule strongly cationic in aqueous media.
Functionally the combination of high hydrogen‑bond donor/acceptor counts and large TPSA leads to very low partitioning into lipophilic phases and high aqueous solubility; passive membrane permeability is therefore poor and systemic exposure after oral dosing is minimal. Glycosidic linkages make the molecule susceptible to acid‑ or enzyme‑catalyzed hydrolysis under strongly acidic or enzymatic conditions, while the polyhydroxylated scaffold confers relative stability to mild aqueous environments and to oxidation in the absence of strong oxidants. Paromomycin is used clinically as an antibacterial and antiprotozoal agent (notably for intestinal amebiasis and visceral leishmaniasis), typically administered as a water‑soluble salt in oral and parenteral formulations.
Common commercial grades reported for this substance include: EP.
Basic Physicochemical Properties
Density and Solid-State Form
Physical description: Solid.
No experimentally established value for this property is available in the current data context.
Melting Point
No experimentally established value for this property is available in the current data context.
Solubility and Dissolution Behavior
Measured solubility (experimental): 7.97e+01 \(\mathrm{g}\,\mathrm{L}^{-1}\). The exceptionally high aqueous solubility is consistent with the molecule's multiple ionizable amino groups and numerous hydroxyls (hydrogen bond donor count = 13; hydrogen bond acceptor count = 19), which promote strong solvation in water. In practice paromomycin is often supplied and formulated as sulfate salts to improve crystalline handling and hygroscopic properties; as an oral agent it remains largely unabsorbed from the gastrointestinal tract, which is exploited therapeutically for luminal protozoal infections.
Collision cross section data (ion mobility): 239.1 Ų [M+H]+ and 237.7 Ų [M+Na]+ (CCS Type: TW; calibrated method), useful for analytical method development and identity confirmation in LC–MS/IM workflows.
Chemical Properties
Acid–Base Behavior and Qualitative pKa
Paromomycin contains multiple aliphatic amino groups that behave as basic sites and will be protonated across acidic to neutral pH ranges, producing a polycationic species in aqueous solution. This extensive protonation accounts for low lipophilicity and high aqueous solvation; consequently the compound exhibits low membrane permeability and limited systemic absorption following oral administration.
No experimentally established numeric \(\mathrm{p}K_a\) values for individual ionizable centers are available in the current data context.
Reactivity and Stability
At the class level, aminoglycoside glycosides are generally stable under neutral, dry, and refrigerated storage conditions but are susceptible to hydrolysis of glycosidic bonds under strong acid or enzymatic conditions; strong oxidizing agents and prolonged exposure to high temperatures and moisture can promote degradation. Paromomycin’s multitude of hydroxyl and amino functionalities make it hygroscopic and sensitive to formulation excipients that alter pH. For formulation and analytical development, avoid acid extremes and strong oxidants; stability-indicating assays should monitor glycoside cleavage and deamination products.
Molecular Parameters
Molecular Weight and Formula
Molecular formula: \(\ce{C23H45N5O14}\)
Molecular weight: 615.6 \(\mathrm{g}\,\mathrm{mol}^{-1}\)
Exact mass: 615.29630113
Monoisotopic mass: 615.29630113
Additional computed descriptors: topological polar surface area (TPSA) = 347; heavy atom count = 42; formal charge = 0 as a neutral base (protonation state in solution is polycationic); complexity = 870; defined atom stereocenter count = 19.
LogP and Structural Features
Computed XLogP3‑AA: -8.7 (dimensionless). The very negative logP reflects extreme hydrophilicity driven by many hydrogen‑bond donors/acceptors (H‑bond donor count = 13; H‑bond acceptor count = 19) and the absence of lipophilic substituents. The high TPSA further predicts low passive transcellular permeability and favors retention in aqueous compartments.
Rotatable bond count = 9, indicating limited large‑scale conformational flexibility relative to small, linear molecules but substantial local conformational freedom in the sugar linkages.
Structural Identifiers (SMILES, InChI)
SMILES: C1[C@H]([C@@H]([C@H]([C@@H]([C@H]1N)O[C@@H]2[C@@H]([C@H]([C@@H]([C@H](O2)CO)O)O)N)O[C@H]3[C@@H]([C@@H]([C@H](O3)CO)O[C@@H]4[C@@H]([C@H]([C@@H]([C@@H](O4)CN)O)O)N)O)O)N
InChI: InChI=1S/C23H45N5O14/c24-2-7-13(32)15(34)10(27)21(37-7)41-19-9(4-30)39-23(17(19)36)42-20-12(31)5(25)1-6(26)18(20)40-22-11(28)16(35)14(33)8(3-29)38-22/h5-23,29-36H,1-4,24-28H2/t5-,6+,7+,8-,9-,10-,11-,12+,13-,14-,15-,16-,17-,18-,19-,20-,21-,22-,23+/m1/s1
InChIKey: UOZODPSAJZTQNH-LSWIJEOBSA-N
(Note: SMILES, InChI and InChIKey are provided for unambiguous connectivity and stereochemistry reference in cheminformatics workflows.)
Identifiers and Synonyms
Registry Numbers and Codes
CAS Registry Number: 41-19-9
Other registry and identifier codes (as reported): UNII = 61JJC8N5ZK; ChEBI = CHEBI:7934; ChEMBL = CHEMBL370143; DrugBank = DB01421; DSSTox Substance ID = DTXSID8023424; HMDB = HMDB0015490; KEGG IDs = C00832, D07467; ATC code = A07AA06.
Synonyms and Brand-Independent Names
Reported synonyms include: Paromomycin; Paramomycin; Aminosidin; Aminosidine; Monomycin; Neomycin E; Paromomycine; Paromomicina; Humatin; Estomycin; Catenulin. Illicit or deprecated synonyms appear in legacy lists and should be cross‑checked during procurement.
Industrial and Pharmaceutical Applications
Role as Active Ingredient or Intermediate
Paromomycin functions as an antibacterial and antiprotozoal active ingredient. Clinically it is used for treatment of intestinal amebiasis and visceral leishmaniasis; due to negligible systemic absorption after oral administration it is particularly suited for luminal infections. Mechanistically it binds to the A site of 16S ribosomal RNA in the bacterial 30S subunit, causing misreading of mRNA and inhibition of protein synthesis.
Formulation and Development Contexts
Typical clinical formulations include oral liquid and solid dosage forms and parenteral preparations when indicated; reported formulation strengths include "125 mg per 5 mL as sulfate" (oral liquid), "250 mg as sulfate" (oral solid), and "750 mg paromomycin base (as sulfate)" for intramuscular injection. Formulation strategy leverages the high aqueous solubility and the compound's low oral bioavailability for luminal targeting. Salt selection (sulfate) is commonly used to control crystallinity, hygroscopicity, and batch‑to‑batch handling.
Specifications and Grades
Typical Grade Types (Pharmaceutical, Analytical, Technical)
Typical grade categories for active pharmaceutical ingredients apply qualitatively: pharmaceutical (pharmacopoeial) grade for clinical manufacture, analytical reference standards for assay and release testing, and technical grade for non‑clinical research. Where pharmacopeial monographs exist, the sulfate salt is frequently the specified form for dosage forms.
Reported commercial grade tag: EP.
General Quality Attributes (Qualitative Description)
Qualitative quality attributes include identity (structure and stereochemistry), assay of active base or salt form, water content/hygroscopicity control, residual solvents (if applicable from synthesis or isolation), microbial limits for oral products, and impurity profile focusing on glycoside cleavage products and desamino/deaminated species. Batch release testing typically emphasizes potency, purity, moisture, and microbiological safety for oral formulations.
Safety and Handling Overview
Toxicological Profile and Exposure Considerations
As an aminoglycoside, systemic aminoglycoside class effects include potential nephrotoxicity and ototoxicity when significant systemic exposure occurs; however, paromomycin’s poor gastrointestinal absorption markedly reduces systemic exposure after oral dosing and therefore lowers the risk of systemic toxicity for oral administration. Drug‑induced liver injury annotation for paromomycin is reported as "No‑DILI‑Concern." During lactation the low oral absorption suggests minimal exposure to breastfed infants.
Exposure control measures should follow standard pharmaceutical handling: avoid inhalation of dust (if in powdered form), minimize skin and eye contact, and employ appropriate PPE (gloves, eye protection, respiratory protection for dusty operations). For detailed hazard, transport and regulatory information, users should refer to the product‑specific Safety Data Sheet (SDS) and local legislation.
Storage and Handling Guidelines
Store in a tightly closed container in a cool, dry place away from strong oxidizers and excessive heat. Protect from moisture and prolonged exposure to humidity to reduce hydrolysis or desiccation issues. For formulation and stability studies, control pH and ionic strength in aqueous preparations to minimize glycosidic cleavage; refrigerated storage of aqueous formulations may be indicated by the manufacturer. For detailed handling and storage conditions consult the product‑specific SDS and applicable pharmacopeial specifications.
