Flexible metal–organic frameworks (MOFs) are dynamic materials that combine long-range structural order with reversible stimulus-responsive phase transitions. In this study, we report the synthesis and characterization of two isoreticular flexible MOFs, TPPM-CPW(Me) and TPPM-CPW(Ph), constructed by combining the ligand tetra-4-(4-pyridyl)phenylmethane (TPPM) with specific Cu(II) paddle-wheel (CPW) secondary building units (SBUs). These MOFs exhibit reversible transitions between open- and closed-pore forms triggered by external stimuli, such as temperature- and pressure-induced guest removal and uptake. The stability of these frameworks is influenced by the residual equatorial groups on the Cu(II) SBUs, with phenyl-functionalized TPPM-CPW(Ph) displaying dynamic behavior characteristic of third-generation soft porous crystals. Notably, TPPM-CPW(Ph) exhibited high adsorption affinity toward fluorinated guests, including SF₆ and volatile anesthetics (VAs) such as desflurane and sevoflurane. This material, when used in solid-phase microextraction (SPME) as fiber coating for the preconcentration of these VAs in air, outperformed commercial CAR/PDMS fibers, underscoring the potential of these versatile flexible MOFs in addressing environmental challenges associated with the use of volatile fluorinated compounds.