The molecular structure and crystal form of L-arginine HCl

L-Arginine HCl (L-Arginine Hydrochloride, molecular formula C₆H₁₄N₄O₂·HCl, CAS No. 1119-34-2) is a stable salt compound formed by the reaction of L-arginine with hydrochloric acid. Its molecular structure is derived from the amino acid backbone of L-arginine combined with protonation and salt formation processes, while its crystal morphology is jointly determined by intermolecular hydrogen bonds, ionic bonds, and molecular packing modes. A systematic analysis is presented below.

I. Molecular Structure

1. Structural Basis of the Parent L-Arginine

As a basic α-amino acid, L-arginine contains an α-amino group (-NH₂), an α-carboxyl group (-COOH), and a side-chain guanidino group (-NH-C(=NH)-NH₂) in its molecule. The chiral center is the α-carbon atom, with an L-configuration (consistent with the chirality of L-alanine, corresponding to the absolute S-configuration). Its structural backbone is represented as NH₂CH(COOH)CH₂CH₂CH₂NHC(=NH)NH₂.

2. Salt Formation and Protonation Characteristics of the Hydrochloride

When L-arginine reacts with hydrochloric acid, protons preferentially bind to the nitrogen atoms of the α-amino group and the side-chain guanidino group, forming a doubly protonated cation (C₆H₁₆N₄O₂²⁺). This cation then combines with chloride ions (Cl⁻) via ionic bonds to form an electrically neutral salt molecule. Among these functional groups, the guanidino group exhibits strong basicity (pKa ≈ 12.5), resulting in a high and stable degree of protonation. The α-amino group (pKa ≈ 9.0) is also fully protonated, while the α-carboxyl group exists in the form of a carboxylate anion (-COO⁻). This forms a typical structural pattern of "inner salt plus external ionic bonds".

3. Bond Lengths and Spatial Conformation

The α-carbon atom adopts a tetrahedral configuration, with bond lengths consistent with the characteristics of typical C-N, C-C, and C-O bonds. For instance, the bond length of C(α)-N (amino group) is approximately 1.47 Å, the bond length of C(α)-C (carboxyl group) is around 1.52 Å, and the bond length of the C=N double bond in the guanidino group is about 1.32 Å. The molecule as a whole assumes a flexible chain-like conformation, where the tetramethylene side chain can undergo torsion to varying degrees. In the crystal state, this chain is fixed into a specific dominant conformation through intermolecular interactions.

4. Intermolecular Forces

The structural stability of the crystal is mainly maintained by hydrogen bonds and ionic bonds. The hydrogen atoms of the protonated amino and guanidino groups act as hydrogen bond donors, forming N-H…O and N-H…Cl hydrogen bonds with the carboxylate oxygen atoms and chloride ions of adjacent molecules, respectively. The bond lengths of these hydrogen bonds mostly range from 2.8 to 3.2 Å. In addition, chloride ions form a coordination network with multiple protonated nitrogen atoms via ionic bonds, further enhancing the stability of the crystal.

II. Crystal Morphology

1. Crystal System and Unit Cell Parameters

The crystals of L-arginine HCl belong to the orthorhombic system, with the space group P2₁2₁2₁. The typical unit cell parameters (at 25℃) are as follows: a ≈ 5.38 Å, b ≈ 12.02 Å, c ≈ 16.84 Å, with a unit cell volume of approximately 1090 ų. Each unit cell contains 4 molecules, which is consistent with the common packing characteristics of amino acid salt crystals.

2. Appearance and Crystallization Habit

Industrial-grade and reagent-grade L-arginine HCl are mostly white, odorless acicular or columnar crystals. The crystal morphology is significantly affected by crystallization conditions. In slowly cooled aqueous solutions, slender acicular crystals are prone to form; under conditions of high concentration and rapid crystallization, the crystals tend to be short columnar or prismatic. The crystals exhibit a certain degree of brittleness, with no obvious cleavage planes, and their surfaces show a glassy or greasy luster.

3. Effects of Crystallization Conditions on Morphology

Solvent Effects: Crystallization in pure water systems tends to produce acicular crystals. Adding a small amount of organic solvents such as ethanol or isopropanol can inhibit the longitudinal growth of crystals, resulting in thicker columnar crystals with a more uniform particle size distribution.

Temperature and Concentration Effects: At low temperatures (0–10℃) and high concentrations, the crystallization rate is fast, easily leading to the formation of fine crystal aggregates. At room temperature (20–30℃) with slow solvent evaporation, large-grained, high-purity crystals can be obtained, which are suitable for structural analysis techniques such as X-ray diffraction.

pH Effects: The pH of the crystallization system should be controlled within the range of 2–4. Under this condition, L-arginine is fully protonated and forms stable crystals with chloride ions. A too high pH may cause the precipitation of free L-arginine, while an excessively low pH may result in rough crystal surfaces and reduced purity due to excess hydrochloric acid.

4. Correlation Between Physical Properties and Crystal Structure

The crystal density is approximately 1.42 g/cm³, which stems from the dense packing of molecules. It has good water solubility (solubility ≈ 200 g/L at 25℃), attributed to the easy dissociation of ionic bonds and hydrogen bonds in the crystal in water, forming hydrated ions. The crystal also has high thermal stability, remaining undecomposed below 180℃. When heated above 200℃, it will gradually lose crystal water (if it is a hydrate) and undergo decarboxylation and deamination reactions.