Introduction
C3H7NO3 is the empirical molecular formula of a small organic compound that contains three carbon atoms, seven hydrogen atoms, one nitrogen atom, and three oxygen atoms. Within the broader context of organic chemistry, this formula is shared by a number of structurally distinct molecules, all of which are related to amino acid chemistry and to hydroxycarboxylic acids. The most common isomer is a beta‑hydroxy amino acid, β‑hydroxyalanine, which carries a carboxyl group, an amine group, and a hydroxyl group on the same carbon chain. Because the functional groups are situated on different carbon atoms, the compound exhibits both amino acid and hydroxy acid characteristics, making it a useful structural motif in biochemistry and in synthetic chemistry.
The molecular formula C3H7NO3 also appears in several other isomers that differ by the relative positions of the hydroxyl and amine substituents along the propionic backbone. These isomeric variations influence physical properties such as solubility, melting point, and pKa values, as well as reactivity toward enzymatic transformations and chemical derivatization. In this article, the formula is discussed both as a descriptor of the molecular composition and as a gateway to the diverse chemistry that arises from the associated structural isomers.
Structural Isomers
β‑Hydroxyalanine
The principal isomer, β‑hydroxyalanine, is formally named 2‑hydroxy‑3‑aminopropanoic acid. Its structure consists of a propionic acid backbone in which the second carbon bears a hydroxyl group and the third carbon bears the amino group. The arrangement can be written as HO–CH2–CH(NH2)–COOH. In solution, β‑hydroxyalanine exists predominantly in its zwitterionic form, where the carboxylate is deprotonated and the amino group is protonated, resulting in a neutral overall charge.
γ‑Hydroxyalanine
An alternative arrangement, 3‑hydroxy‑2‑aminopropanoic acid, places the hydroxyl group on the first carbon and the amino group on the second. The structural formula is HO–CH(NH2)–CH2–COOH. While both isomers share the same empirical formula, the change in functional group positions alters their physicochemical behavior, including relative acidity and basicity of the functional groups. γ‑Hydroxyalanine is less commonly encountered in natural contexts but can be synthesized via regioselective hydroxylation of 2‑aminopropanoic acid.
General Chemistry and Physical Properties
Molecular Characteristics
The molecular weight of any isomer with the formula C3H7NO3 is 105.09 g mol⁻¹. The molecules are small, colorless solids at room temperature, and are highly soluble in water and polar organic solvents such as methanol and ethanol. In aqueous solution, the presence of both acidic and basic functional groups gives rise to two distinct pKa values: one for the carboxyl group (~2.5–3.0) and one for the amino group (~8.0–9.0). The neutral form of β‑hydroxyalanine has a melting point around 130 °C, whereas the γ‑isomer melts slightly higher, near 140 °C, reflecting differences in hydrogen‑bonding patterns in the crystal lattice.
Spectroscopic Features
Infrared spectroscopy reveals characteristic absorptions for the carboxylate carbonyl (~1715 cm⁻¹), carboxylate asymmetric stretch (~1620 cm⁻¹), hydroxyl stretch (~3300 cm⁻¹), and N–H stretch (~3350 cm⁻¹). Proton nuclear magnetic resonance (^1H NMR) spectra display signals corresponding to methylene or methine protons adjacent to the hydroxyl and amino substituents, typically in the range 3.5–4.5 ppm. Carbon‑13 NMR signals for the carboxyl carbon appear near 170 ppm, while the carbons bearing the hydroxyl and amino groups resonate between 40 and 60 ppm, depending on the isomer. Mass spectrometric analysis shows a base peak at m/z 58, corresponding to the C2H5NO⁺ fragment, and a prominent ion at m/z 104, representing the loss of water from the parent ion.
Synthetic Routes
Laboratory Preparation
- Starting from commercially available 2‑aminopropanoic acid, a selective hydroxylation can be achieved by treating the amino acid with a peracid (e.g., meta‑chloroperbenzoic acid) in the presence of a Lewis acid catalyst. The reaction proceeds at 0 °C to moderate temperatures and yields a mixture of hydroxylated products that is then separated by ion‑exchange chromatography.
- Alternatively, enzymatic hydroxylation using recombinant cytochrome P450 enzymes engineered for regioselective activity has been demonstrated in vitro. The enzyme catalyzes the addition of a hydroxyl group to the second or third carbon of the amino acid, yielding β‑ or γ‑hydroxyalanine, respectively. Reaction conditions typically involve a buffer at pH 7.5, NADPH as a co‑factor, and an oxygen atmosphere.
Industrial Synthesis
Scale‑up production of β‑hydroxyalanine for use as an intermediate in pharmaceutical synthesis generally follows a two‑step approach. First, 2‑amino‑3‑propanol is prepared via reductive amination of propanal with ammonia in the presence of a catalyst such as Raney nickel. In the second step, the aldehyde is converted to the carboxylic acid through a Pinnick oxidation using sodium chlorite in a buffer of sodium dihydrogen phosphate. The final product is isolated by crystallization from a methanol–water mixture.
Biological Role
Metabolic Pathways
β‑Hydroxyalanine can be generated in vivo as a side product of the oxidative metabolism of alanine and other small amino acids. The enzyme alanine oxidase, which participates in the catabolism of amino acids in certain bacteria, can introduce a hydroxyl group at the β‑position. In higher organisms, the compound is generally considered a non‑proteinogenic amino acid and is not incorporated into proteins during translation. Nonetheless, it can serve as a precursor for the synthesis of cyclic compounds and as an inhibitor of specific metabolic enzymes, thereby modulating pathways such as the urea cycle and glutamine synthesis.
Pharmacological Significance
Due to its structural similarity to the naturally occurring β‑hydroxy amino acids found in certain peptide natural products, β‑hydroxyalanine is employed as a building block in the synthesis of analogs of antimicrobial peptides. The hydroxyl functionality allows for the introduction of further functional groups, such as acetyl or benzyl esters, enhancing membrane permeability or protease resistance. Some derivatives of β‑hydroxyalanine have been evaluated as inhibitors of the enzyme carbonic anhydrase, where the hydroxyl group participates in a metal‑binding interaction with the zinc ion in the active site.
Applications
Pharmaceutical Development
The hydroxylated amino acid scaffold is used in the design of prodrugs for poorly soluble drugs. By conjugating a therapeutic agent to the carboxylate of β‑hydroxyalanine, the resulting ester can improve aqueous solubility and facilitate oral absorption. After cellular uptake, esterases hydrolyze the linkage, releasing the active drug and β‑hydroxyalanine as a harmless metabolite.
Polymer Chemistry
β‑Hydroxyalanine derivatives are incorporated into polymer backbones to introduce flexible side chains that can modulate glass transition temperatures and mechanical strength. For example, polyesters containing hydroxyalanine units have been shown to exhibit improved toughness compared with homopolymers of poly(propylene glycol). In addition, the presence of an amine group allows post‑polymerization functionalization through amide or carbamate formation, enabling the synthesis of block copolymers with tailored properties.
Analytical Reagents
The hydroxyl and amino groups make C3H7NO3 isomers valuable reagents in quantitative analysis. They can act as internal standards for mass spectrometric determination of carboxylic acids because their fragmentation patterns are predictable and distinct. Moreover, the compound is employed in derivatization protocols for the detection of aldehydes and ketones; the amino group forms a Schiff base with carbonyl compounds, while the hydroxyl group can be protected or deprotected during the procedure.
Safety and Handling
Health Hazards
In general, the isomers with formula C3H7NO3 are considered low‑to‑moderate toxicological risk. Inhalation or dermal exposure to fine dust should be avoided because the material can cause irritation of the skin, eyes, and respiratory tract. Ingestion of large quantities may lead to gastrointestinal distress, primarily due to the acidic nature of the carboxyl group. Acute toxicity data from animal studies indicate an LD50 for oral exposure in rodents that exceeds 2000 mg kg⁻¹, suggesting a relatively wide safety margin when handled in typical laboratory concentrations.
Regulatory Status
Because the compound is not listed as a regulated chemical under the United Nations Chemical Weapons Convention, it does not require special classification for transport or storage. However, it falls under the scope of general chemical safety regulations, and employers are advised to maintain a material safety data sheet (MSDS) that includes information on personal protective equipment, spill handling, and first aid measures.
Analytical Methods
Chromatographic Techniques
High‑performance liquid chromatography (HPLC) with a reverse‑phase C18 column and a mobile phase consisting of water and acetonitrile, both buffered with formic acid, provides good separation of the β‑ and γ‑isomers. The retention times differ by several minutes, allowing for quantitative analysis. Gas chromatography (GC) can be employed after derivatization of the carboxyl group to a tert‑butyldimethylsilyl ester, increasing volatility and stability at the injector temperature.
Spectroscopic Identification
Proton nuclear magnetic resonance spectroscopy is the most informative method for determining the position of the hydroxyl and amine substituents. In the β‑isomer, the methylene protons adjacent to the hydroxyl group appear as a doublet of doublets at 3.85 ppm, while the methine proton attached to the amino group resonates at 3.70 ppm. The carbonyl carbon shows a distinct resonance at 172.4 ppm in the carbon‑13 spectrum. Infrared spectroscopy confirms the presence of a broad O–H stretch at 3300 cm⁻¹, a sharp N–H stretch at 3350 cm⁻¹, and a strong carbonyl stretch at 1715 cm⁻¹.
Mass Spectrometry
Electrospray ionization (ESI) mass spectra in positive mode show a prominent protonated molecular ion at m/z 106, corresponding to [C3H7NO3 + H]⁺. Fragmentation yields a base peak at m/z 58 (C2H5NO⁺) and a secondary peak at m/z 104, which represents the loss of a water molecule from the protonated parent ion. In negative mode, the deprotonated carboxylate ion appears at m/z 104, and a further fragment at m/z 82 is often observed due to the loss of a hydroxyl group.
Environmental Impact
The compound degrades readily in aqueous environments through microbial metabolism, primarily via oxidoreductase enzymes that convert the hydroxyl group into a ketone or remove the amino group to form α‑ketoglutarate. In soil, it is rapidly assimilated by microorganisms, and no persistent bioaccumulation has been reported. Its biodegradability and low toxicity make it an acceptable material for use in agricultural applications where it serves as a temporary nutrient source for bacterial cultures.
Future Research Directions
Investigations into the catalytic activity of engineered enzymes that produce β‑hydroxyalanine in a selective manner may open new pathways for the biosynthesis of complex natural products. Additionally, the incorporation of the hydroxylated amino acid into polymer matrices remains a promising area for the development of biodegradable plastics with improved mechanical properties. Finally, exploring the potential of β‑hydroxyalanine as a ligand in coordination chemistry may yield novel metal complexes with applications in catalysis and material science.
Conclusion
The small, multifunctional molecule with formula C3H7NO3 serves as a versatile component in chemical synthesis, biology, and materials science. Its ease of synthesis, clear spectroscopic signatures, and low toxicity profile make it a valuable tool for chemists across disciplines. Continued research into its application as a building block for complex molecules and as a subject of enzyme‑catalyzed transformations will likely broaden its utility further in the coming years.
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