Homogeneous Molecular Systems are Positively Cooperative, but Charged Molecular Systems are Negatively Cooperative

Abstract

Molecular systems bound together through noncovalent interactions are ubiquitous in nature, many of which are involved in essential life processes, yet little is known about the principles governing their structure, stability, and function. Cooperativity as one of the intrinsic properties in these systems plays a key role. In this work, on the basis of our recent quantification scheme of the cooperativity effect, we present a general pattern to identify which systems are positively cooperative and which are negatively cooperative. We show that cooperativity in homogeneous molecular systems is positive, but cooperativity in charged molecular systems is negative. We also employ analytical tools from energetics and information perspectives to appreciate the origin of the cooperativity effect. We find that positive cooperativity is dominated by the exchange–correlation interaction and steric effect, whereas negative cooperativity is governed by the electrostatic interaction. Our results should have strong implications for better understanding molecular recognition, protein folding, signal transduction, allosteric regulation, and other processes.

Information‐theoretic approach in density functional theory and its recent applications to chemical problems

“…Using simple atomic and molecular clusters as examples (Scheme ), we showed that both positive and negative cooperativity are possible. We found that cooperativity in charged molecular systems is negative, whereas that in homogeneous molecular systems is positive (Figure ) . We additionally unveiled that negative cooperativity is dictated by the electrostatic interaction but positive cooperativity is governed by the exchange‐correlation interaction and steric effect.…”

“…For systems with NCI, which are characterized by the cooperativity effect due to the competition and compromise among two or more interactions, we recently quantify the cooperativity effect with the interaction energy and analyzed the nature and origin of the cooperativity effect with ITA and other density‐based quantities . Using simple atomic and molecular clusters as examples (Scheme ), we showed that both positive and negative cooperativity are possible.…”

“…We additionally unveiled that negative cooperativity is dictated by the electrostatic interaction but positive cooperativity is governed by the exchange‐correlation interaction and steric effect. From the ITA perspective, these two categories of cooperativity behaviors were tremendously different …”

“…The optimized structure for six cluster models with n = 20 as illustrative examples. (Reprinted with permission from Reference . Copyright 2019 American Chemical Society)…”

Cooperativity in alkane‐1,2‐ and 1,3‐polyols: NMR, QTAIM, and IQA study of O─H…OH and C─H…OH bonding interactions

“…The term “cooperativity” is widely used in chemistry to indicate the non‐additivity of the effects of generally similar or identical groups or molecules, interacting so as to produce an overall variation in a phenomenon or property which is greater than the sum of their individual effects 1–5 . In the context of hydrogen bonding, this implies that bond strengths should be mutually enhanced, that is, that the strengths of two interacting bonds should be higher than those of the isolated bonds 6 .…”