In this work, we studied the effect of connecting units in three generations of two series of dendritic molecules on the structural properties and the complexation behavior based on hydrogen bonding between the dendrimer cores and two different guest molecules. Our molecular simulations revealed that the geometry of the core strongly influences the generational growth of these macromolecules, ultimately resulting in similar, flower-like, shape-consistent macromolecular hosts. The calculations of the free energies of binding between all dendrimers and their guests, obtained by applying the so-called MM/PBSA methodology, are in utter agreement with the corresponding experimental values. Host-guest interactions and clathration in a dendritic architecture are intriguing properties of dendrimers, especially when the location of the guest molecules can be controlled and predetermined by the incorporation of specific binding sites utilizing hydrophobic interactions, hydrogen-bonding, or a metal ion coordination site.