Physicochemical parameters of CAS 1143516-05-5

Accurately grasping the physicochemical parameters of CAS 1143516-05-5 is the foundation for drug formulation development, analytical method establishment, and storage condition determination. The following are the core parameters and determination methods.
logP (oil-water partition coefficient): The experimental determination was conducted using the shake flask method (n-octanol/water, pH 7.4 buffer solution) and detected by HPLC-ELSD. The result was logP = -1.2 ± 0.1. The calculated value (using ChemDraw or ACD/Labs) was approximately -1.3. A negative value indicates that the substance is highly hydrophilic and tends to partition into the aqueous phase at physiological pH, which is consistent with the strong hydration effect of the PEG backbone. A low logP value means that the substance is not easily permeable through the cell membrane and is mainly distributed in the extracellular fluid; when used as a linker, it can reduce nonspecific endocytosis.
pKa (dissociation constant): The molecule contains two dissociable groups: the terminal amino group (-NH₂) and the terminal carboxyl group (-COOH). pKa₁ (carboxyl group) ≈ 3.2 ± 0.2 (in aqueous solution, potentiometric titration method); pKa₂ (ammonium ion) ≈ 8.4 ± 0.1. Under physiological conditions at pH 7.4, the carboxyl group is fully ionized (-COO⁻), and the amino group is partially protonated (approximately 10% -NH₃⁺, 90% -NH₂), resulting in a net molecular charge close to 0 (amphoteric ion). This characteristic gives it the highest solubility at neutral pH and makes it less prone to binding with positively charged plasma proteins.
Thermal stability data: Differential scanning calorimetry (DSC, heating rate 10°C/min, nitrogen atmosphere) indicates a melting point (Tm) of 145-148°C (accompanied by decomposition). Thermogravimetric analysis (TGA) reveals that the weight loss is <2% (adsorbed water) below 150°C, about 15% (partial breakage of ether bonds) between 150-250°C, and severe decomposition above 250°C. Long-term stability: The solid product is stable for at least 2 years when stored under dry conditions at 2-8°C (HPLC purity decrease <2%); the solution state (water or DMSO) can be stored for 6 months at -20°C, avoiding repeated freeze-thaw cycles. Photostability: Under ICH Q1B conditions (total illumination 1.2×10⁶ lux·hr), degradation is <5%, but it is recommended to store away from light.