Competing Dispersive Interactions: From Small Energy Differences to Large Structural Effects in Methyl Jasmonate and Zingerone

Abstract

Modern structural studies of biologically relevant molecules require an exhaustive interplay between experiment and theory. In this work, we present two examples where a poor choice of the theoretical method led to a misinterpretation of experimental results. We do that by performing a rotational spectroscopy study on two large and flexible biomolecules: methyl jasmonate and zingerone. The results show the enormous potential of rotational spectroscopy as a benchmark to evaluate the performance of theoretical methods.

Bond Length Alternation Observed Experimentally: The Case of 1H‐Indazole

“…On the other hand, the geometries determined in the gas phase, mainly by rotational spectroscopy, are for molecules free from interactions of any kind (solvent, crystal packing, etc.). Furthermore, rotational spectroscopy results constitute benchmarks for evaluating the performance of theoretical calculations …”

“…Furthermore, rotational spectroscopyr esultsc onstituteb enchmarksf or evaluating the performance of theoretical calculations. [35,36] In the case of indazole, [70] there are two tautomers, the 1Hand the 2H-, as drawn in Figure 1. At the MP2/cc-pVTZ level, the 1H-tautomer is more stable than the 2H-tautomer by 13.6 kJ mol À1 .T his is consistent with, although al ittle lower than, previous calculations: 33.5 kJ mol À1 at 4-21G; [55] 17.2 kJ mol À1 at MP2/6-31G*; [71] 21.4 kJ mol À1 at B3LYP/6-31G*; [72] 20.6 kJ mol À1 at B3LYP/6-311G(d,p); [73] 20.3 kJ mol À1 at G2, [5] and 22.4 kJ mol À1 at QCISD/6-31G(d,p) (present work).…”

Binding Site Switch by Dispersion Interactions: Rotational Signatures of Fenchone–Phenol and Fenchone–Benzene Complexes

“…T he difficulties associated with balancing competing weaki nteractions by theoretical methods have been reported for other molecular systems, including the overestimation of CÀH•••p interactions by MP2 and challenges in describing the dispersion interactions. [35,36] Interestingly,a lthough the primary interaction in the fenchone-phenol and fenchone-benzene complexes is different, the arrangemento fp henol/benzene with respect to fenchone in their respective global minima, FPHE1a nd FBEN1, is very similar,w ith their aromatic rings interacting with one of the C6 hydrogen atoms. This arrangementc ontrasts with the preferred binding site of the 1:1c omplexes of fenchone with water [17] and ethanol.…”

Exploring Caffeine–Phenol Interactions by the Inseparable Duet of Experimental and Theoretical Data

“…[37][38][39][40] Certainly,i th as become very populara mong microwave spectroscopists because it is provent oy ield accurate predictionso nt he structure of stable molecules. [41] As shown below,a lthough all computational levels agreed in the prediction of the mosts table structure, a large dispersion was observed for the relative stabilityo ft he local minima; this complicates the assignment and highlights the difficulty of modeling systems formed by noncovalent interactions.…”

“…The third functional, B3LYP corrected by empirical dispersion (ED=GD3BJ), belongs to a completely different family and was reported to yield outstanding results for systems containing noncovalent interactions . Certainly, it has become very popular among microwave spectroscopists because it is proven to yield accurate predictions on the structure of stable molecules . As shown below, although all computational levels agreed in the prediction of the most stable structure, a large dispersion was observed for the relative stability of the local minima; this complicates the assignment and highlights the difficulty of modeling systems formed by noncovalent interactions.…”