The structural characterization of complexes [(Mn4Mn22III)-Mn-II(pdol)(12)(OCH3)(12)(O)(16)(N-3)(6)] (1) and [Mn-4(II)-Mn-22(III)(pdol)(12)(OCH3)(12)(O)(16)(OH)(2)(H2O)(OCH3)(3)]cen ter dot CIO(4)center dot 5CH(3)OH (2), where pdol(2-) is di-2-pyridyl methanediol, reveals that each has a metallacryptand shell that encapsulates a manganese oxide core. Variable temperature direct current magnetic susceptibility measurements on 2 indicate a paramagnetic ground state that results from an overall antiferromagnetic interaction in the cluster, with chi T values decreasing from 300 K (51.2 cm(3) K mol(-1)) to 2 K (19.8 cm(3) K mol(-1)). Variable-temperature alternating current magnetic susceptibility measurements imply that both 1 and 2 behave as single-molecule magnets. Fitting the frequency-dependent out-of-phase magnetic susceptibility to the Arrhenius equation yields an effective energy barrier, U-eff, to magnetization relaxation of 16.5 +/- 0.7 K (11.5 +/- 0.5 cm(-1)) for 1 and 36.2 +/- 2.0 K (25.1 +/- 1.4 cm(-1)) for 2. The larger value for 2 is in agreement with the lower molecular symmetry, larger magnetoanisotropy, and higher ground spin state of 2 compared to those of 1. This observation suggests a new strategy for increasing the blocking temperatures in high-nuclearity manganese clusters.