Based on this comprehensive analysis integrating experimental 1 H NMR data, structural planarity measurements, and multiple computational indicators (NICS, GIMIC, HOMA/HOMAc, and AV1245/AVmin), we determined that the antiaromatic character of these systems decreases in the order 1e > 1d > 1a > 1b (≈ 1f) > 1c. This trend consistently demonstrates the significant influence of meso-substituents on the antiaromaticity of isophlorins, primarily through their effect on macrocycle planarity and the extent of π-conjugation.