Chemical and physical properties of polymeric species in solution strongly depend on their structure, which can be modulated by covalently linking substituents of different solubility. In this work, the effect of changing the interaction strength and fractional loading of hydrophobic substituents on semi-flexible hydrophilic polymers of varying chain length is studied by means of Monte Carlo simulations and coarse grained model potentials. The latter are chosen in order to provide a more factual representation of a chain in diluted solution, introducing substituent flexibility and realistic torsional and bending potentials. Upon increasing the number and the interaction strength of the substituents, our results indicate a less steep rise of the chain gyration radius and "end to end" distance for the chain length than predicted for an unsubstituted polymer in an almost good solvent. Moreover, a "disordered to compact" structural transition appears. In parallel, the formation of hydrophobic nuclei and the consequent appearance of flexible polymer loops grafted to the semi-rigid cores is witnessed. The core formation resembles a nucleation phenomenon, where the change in the interaction between the substituents modulates the free energy surface for the aggregation process similarly to the change in chemical potential. Interestingly, it has been found that a single chain containing a sufficiently high number of interacting substituents may give rise to the formation of multiple cores, suggesting that the chain stiffness may play a role in defining the structure of the free energy minimum. (C) 2010 Elsevier Ltd. All rights reserved.