Crystallographic characterization and polymorphism in a calcium-based porphyrinic MOF with biomedical potential

TL;DR

This paper describes the synthesis and characterization of a calcium-based MOF with TCPP linkers, showing structural polymorphism and improved stability for biomedical uses like cancer therapy.

Contribution

The study reports a novel calcium-based porphyrinic MOF with polymorphic behavior and enhanced stability for biomedical applications.

Findings

A calcium-based MOF with TCPP was synthesized and crystallized in two distinct polymorphic forms.

The second polymorph showed improved water and pH stability, suitable for biological environments.

The structural sensitivity of calcium–porphyrin frameworks to crystallization dynamics was demonstrated.

Abstract

Metal–organic frameworks (MOFs) based on biocompatible metals such as calcium are gaining increasing attention in the biomedical field due to their low toxicity, structural diversity, and potential for drug delivery and photodynamic therapy (PDT) [1]. Despite this, calcium-based MOFs incorporating porphyrinic linkers remain rare in the Cambridge Structural Database (CSD). A recent CSD survey conducted in May 2025 revealed fewer than 10 such structures. Among organic linkers, Tetrakis(4-carboxyphenyl) porphyrin (TCPP) stands out for its strong light absorption, high reactive oxygen species (ROS) generation, intrinsic fluorescence, and ability to coordinate with various metals, features that make it highly effective for synergistic PDT and chemotherapy, especially in the treatment of solid tumors [2, 3, 4]. TCPP-based MOFs, particularly those formed with biocompatible metals like calcium or lanthanum, provide enhanced water solubility, minimize aggregation-induced quenching, and improve biocompatibility, essential characteristics for biomedical applications [1].

In this work, we report the synthesis and characterization of a calcium-based MOF assembled with TCPP under solvothermal conditions. The initially isolated phase crystallized in a monoclinic system, [Ca2(OH)2(TCPP)] (1), with unit cell parameters a = 35.15 Å, b = 6.65 Å, c = 15.97 Å, β = 96.396°, and a volume of 3715.0 Å3. Subsequent syntheses yielded a distinct structure with parameters a = 6.90 Å, b = 23.69 Å, c = 17.02 Å, β = 97.37°, and a volume of 2758 Å3, suggesting the formation of a new polymorph. This observed polymorphism, despite identical synthetic conditions, demonstrates the structural sensitivity of calcium–porphyrin frameworks to subtle changes in crystallization dynamics. Notably, the second polymorph exhibited improved water and pH stability, confirmed by PXRD over 12 days in water and 4 days at pH 7.4, making it more appropriate for biological environments. These findings reinforce the potential of calcium– TCPP MOFs as stable, multifunctional platforms for biomedical applications, particularly in cancer therapy where drug loading, biocompatibility, and controlled release are critical.