To gain an extra level of information, we investigated the stability of the intermolecular hydrogen-bonded structures by measuring the temperature dependence of the chemical shifts of the amide protons in the range of 298-328 K in CDCl3. The temperature coefficient Δδ ΔT is primarily affected by alterations in conformational ensembles, which are mainly but not exclusively attributable to changes in hydrogen-bonding patterns. In the vt-NMR experiment performed in CDCl3, small temperature dependencies Δδ ΔT < ± ppb ) can be observed for solvent-exposed NH protons as well as for those that are shielded from solvent and remain shielded over the temperature range of the measurements. Larger temperature dependencies are instead observed if the NH group is shielded from solvent initially but becomes exposed with increasing temperature, thus when intramolecularly hydrogen-bonded conformations unfold as the temperature increases. Variable temperature experiments in CDCl3 for AS4 (Figure , graph) showed Δδ ΔT > -2.4 ppb/K [N(4)-H = -6.67 ppb/K, N(1)-H = -6.00 ppb/K, N(H)-3 = -5.33 ppb/K]. Such values might support the hypothesis of amide protons being initially shielded due to weak IMHB favoured by a cis conformation. In detail, for the amides adjacent to ferrocene, N(4)-H seems to be more initially shielded compared to the counterpart N(3)-H in agreement with the intramolecular pattern of hydrogen bonds discussed above. The temperature coefficient suggests indeed that N(4)-H is more influenced by changes in the local environment compared to N(3)-H, which could be due to the disruption of an additional IMHB in a more stable and populated ensemble. It is reasonable to speculate that N( )-H's potential to form a secondary IMHB with PEG could account for its slightly greater tendency to engage in IMHBs and consequently, this disruption may have a larger effect on its temperature coefficient. In both 14a (Figure ) and AS4, the amide N(2)-Δδ ΔT14a = -1 7 ppb and Δδ ΔTAS4 -2.33 ppb/K) appears to be involved in strong IMHB, as indicated by minimal chemical shift changes and aligned with the small ANMR value. Interestingly, N(1)-H in the methylated analogue of VH032 of AS4 appears to be initially shielded to a greater extent compared to 14a (ANMRAS4 = 0.11 vs ANMR14a 16 and Δδ ΔTAS4 = -6.00 ppb/K vs Δδ ΔT14a = -3.52 ppb/K) possibly due to interactions with the CRBN counterpart in a cis conformation or due to an enhanced shielding effect by the methyl group of MeVH032. Eventually, two-dimensional NOESY spectroscopy was used to gain better insight into the folding patterning of AS4 in CDCl3 and methanol-d4. Table summarises the possible cross-ligand NOEs observed in both solvents as indicated in Figures . The overlap of some peaks, however, hinders the definitive identification of the NOE origins, requiring careful interpretation. Nevertheless, a thorough analysis of the NOESY spectra indicated a higher likelihood of cross-ligand NOEs in CDCl3 than in methanol-d4. This suggests a potential cis configuration of the ferrocene in an apolar environment, but not in a polar one.