Regarding the choice of the controls, we used control conditions (changing the solution pH to unfold the i-motif) and control sequences (mutating bases to thymines, which disrupts base pair interactions). We found caveats in both approaches, indicating that the difference of unfolding voltage alone was also not sufficient to deduce that extra specific intramolecular bonds were present in solution. In practice, one should further investigate how the nature of the acidifying additive influences the gas-phase unfolding even when the solution structure is unchanged. IMS after mass selection and activation in a collision cell might avoid such problem. When designing control sequences, we would recommend changing the base order rather than replacing many bases with thymines. To cope with this base-dependent effect on CCS and unfolding voltage, future work will be devoted to predicticting the "baseline" CIU curve (starting CCS, end CCS, transition voltages) of unstructured control sequences of any composition, length and