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2), in contrast, reflects all nominal differences of the data coordinates to the ideal model function that is implemented in the data evaluation software generally provided with the calorimeter. Since this ideal model excludes all experimentally observed contributions not related to the core supramolecular process, it can lead to massive systematic errors if applied incorrectly. An ideal model, by definition, does not pay attention to any non-ideality inherent in the experimental data. That is why one needs to correct for non-ideality in the data before applying a proposed binding model. Frequently, blank titrations accomplish this only in part. Hence, there is a requirement for, and benefit of, the above adjustments. Another key point to stress is that, in contrast to NMR, calorimetry gives immediate access to the energetics of the system but does so without regard to the structures involved in the supramolecular interaction. Structural information can only be deduced from trend analyses involving the change in energetics that arise from making incremental and well-defined modifications in the host-guest binding system. Thus, in the case of ITC, structural information is inferred far less directly than in the case of NMR, where specific chemical shifts can be monitored, at least in favorable cases. Nonetheless, by using closely related binding partners or varying the solvent while studying the same host-guest combination, ITC can provide a correlation between binding energetics and structure that-at least in theory-complements, rather than rivals, the insights obtained from structure-based NMR spectroscopic analyses.
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