We investigate the magnetic resonance properties and exchange kinetics of guest molecules in a series of hetero-bimetallic capsules, [ConFe4-nL6](4-) (n = 1-3), where L2- = 4,4'-bis[(2-pyridinylmethylene)amino]-[1,1'-biphenyl]-2,2'-disulfonate. H bond networks between capsule sulfonates and guanidinium cations promote the crystallization of [ConFe4-nL6](4-). The following four isostructural crystals are reported: two guest-free forms, (C(NH2)(3))(4)[Co1.8Fe2.2L6]center dot 69H(2)O (1) and (C(NH2)(3))(4)[Co2.7Fe1.3L6]center dot 73H(2)O (2), and two Xe- and CFCl3-encapsulated forms, (C(NH2)(3))(4)[(Xe)(0.8)Co1.8Fe2.2L6]center dot 69H(2)O (3) and (C(NH2)(3))(4)[(CFCl3)Co2.0Fe2.0L6]center dot 73H(2)O (4), respectively. Structural analyses reveal that Xe induces negligible structural changes in 3, while the angles between neighboring phenyl groups expand by ca. 3 degrees to accommodate the much larger guest, CFCl3, in 4. These guest-encapsulated [ConFe4-nL6](4-) molecules reveal Xe-129 and F-19 chemical shift changes of ca. -22 and -10 ppm at 298 K, respectively, per substitution of low-spin Fe-II by high-spin Co-II. Likewise, the temperature dependence of the Xe-129 and F-19 NMR resonances increases by 0.1 and 0.06 ppm/K, respectively, with each additional paramagnetic Co-II center. The optimal temperature for hyperpolarized (hp) Xe-129 chemical exchange saturation transfer (hyper-CEST) with [ConFe4-nL6](4-) capsules was found to be inversely proportional to the number of Co-II centers, n, which is consistent with the Xe chemical exchange accelerating as the portals expand. The systematic study was facilitated by the tunability of the [M4L6](4-) capsules, further highlighting these metal-organic systems for developing responsive sensors with highly shifted Xe-129 resonances.