Comparative pH-Metric Investigation of Stepwise Stability Constants of Phenylephrine Hydrochloride Complexes with Transition and Rare Earth Metal Ions

Abstract

A potentiometric investigation of the sympathomimetic drug phenylephrine hydrochloride (PEH) with selected transition and rare-earth metal ions was conducted using the Calvin–Bjerrum pH titration technique as modified by Irving and Rossotti. Proton–ligand dissociation constants and thermodynamic metal–ligand stability constants (log K₁ and log K₂) were determined at a constant temperature (298.15 K) and ionic strength (μ = 0.1 M NaNO₃). The ligand exhibits two distinct protonation constants corresponding to the sequential deprotonation of its secondary amino and phenolic hydroxyl groups, confirming its bidentate (O, N) coordination topology. Stepwise stability constants of coordination complexes formed with Ni(II), Co(II), Mn(II), Cu(II), Zn(II), Fe(III), Cr(III), La(III), Sm(III), and Ce(III) were evaluated concurrently using pointwise calculation and half-integral graphical methods. Comparative equilibrium analysis revealed that the primary coordination step is uniformly more thermodynamically favourable than the secondary step (log K₁ > log K₂). Transition metal ions exhibited an exceptional affinity profile following the order: Mn(II) < Co(II) < Ni(II) < Cu(II) > Zn(II) directly validates the Irving–Williams series, while Fe(III) displayed maximum stability governed by high charge density. Rare earth metal complexes exhibited moderate stabilities regulated by ionic radius contraction and electrostatic dominance. These findings map the solution coordination chemistry profiles of PEH, offering crucial structural parameters for prospective bioinorganic and pharmaceutical chemistry applications.