The cubic symmetry of octafunctional octaphenylsilsesquioxanes [ROPS, (RC6H4SiO(1.5))8] coupled with a 1 nm diameter offers exceptional potential to assemble materials in three dimensions with perfect control of periodicity and the potential to tailor global properties at nanometer length scales. OPS itself is very inert and insoluble and can only be functionalized via electrophilic reactions with difficulty and with poor substitutional selectivity. However, functionalized OPS products are robust and highly soluble, offering easy purification and processing. In contrast to previous studies, we report here that OPS reacts with ICl at sub-ambient temperatures to provide (following recrystallization) [p-IC6H4SiO(1.5)]8, or I8OPS, in good yields and with excellent selectivity: >99% mono-iodo substitution with >93% para substitution as determined by H2O2/F- cleavage of the Si-C bonds to produce iodophenols. I8OPS in turn can be functionalized using conventional catalytic coupling reactions to provide sets of >93% para-substituted, functionalized compounds (alkynes, alkenes, aryl amines, phosphonates, aryl amines, polyaromatics, etc.), suggesting the potential to develop diverse nano-building blocks for the assembly of a wide variety of materials, some with novel photonic, electronic, and structural properties.