The large molecules 1–3 (69, 90, and 102 atoms, respectively), prepared by cyclotrimerization of enantiomerically pure derivatives of (−)-bornyl acetate, show intense ECD spectra, high optical rotation (OR) values (200–1300, in absolute value) dominated in sign and order of magnitude by the lowest-energy Cotton effects, that is, they are the ideal candidates to test the reliability of our “approximate” (TDDFT/B3LYP/6-31G* or smaller basis set) approach to the calculation of chiroptical properties. As a matter of fact, a correct simulation of the OR values and ECD spectra of 1 and 2 can be obtained even using STO-3G basis set and semiempirical or molecular mechanics input geometries: for 1, at the TDDFT/B3LYP/STO-3G level, the OR values are of the order of 500–550, versus an experimental value ranging between 660 and 690, depending on the solvent. On the contrary, the case of 3 (exp. OR between −1330 and −1500) is really complex (for instance, the OR values range between −3216 and −729 (TDDFT/B3LYP/6-31G* calculations) or −1824 and −444 (TDDFT/B3LYP/STO-3G calculations)), making the comparison between calculated and experimental values more difficult. The behavior of 3 is due to its molecular flexibility, whereas 1 is a really rigid molecules and 2 behaves (vide infra) as it were a rigid system. These observations strongly indicate that the conformational freedom constitutes one of the major difficulties for a correct but simple simulation of the chiroptical properties. Chirality 21:E86–E97, 2009. © 2009 Wiley-Liss, Inc.