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44262-AC6
Theoretical Investigations of the Nature of Pi-Pi Interactions
State-of-the-art theoretical methods have been used to probe the fundamental nature of noncovalent interactions involving aromatic groups. Such noncovalent pi interactions are central to protein folding, drug docking, crystal packing of organics, self-assembly, and many other crucial topics. Our goal is to determine the fundamental rules which govern these interactions and, ultimately, to learn how they can be precisely controlled. With partial support from the PRF, we have pursued the following primary questions:
1. What is the fundamental nature of pi-pi interactions? What are their physical origins (electrostatics, dispersion, etc), their geometrical preferences, their strength, etc? To address this question, we have embarked on a thorough, benchmark-quality theoretical study of the benzene dimer and its derivatives. A feature article in J. Phys. Chem. A (Sinnokrot and Sherrill, 2006) explores these and other issues, particularly what level of theory is required to achieve reliable results for these systems. This article is meant to introduce these issues to a wide audience, and it has been well received (leading to subsequent invitations for an invited feature article in Physical Chemistry Chemical Physics and a pedagogical chapter in Annual Reviews in Computational Chemistry). A complementary paper on CH/pi interactions (Ringer et al, 2006) compares and contrasts perpendicular pi-pi interactions (e.g., T-shaped benzene dimer, which might also be considered a type of aromatic CH/pi interaction) to CH/pi interactions as occur in systems like the methane-benzene, methane-phenol, and methane-indole complexes.
We have also taken up the challenge offered by Schweizer and Dunitz, who argue that the lattice energy of crystalline benzene is the next logical target for high-accuracy computations of prototype pi-pi systems. We are just submitting a paper we have very high-quality values [estimated complete basis set CCSD(T)] for the lattice energy of crystalline benzene. Our error analysis and comparison to experiment indicates that we have achieved "chemical accuracy" in our computations, which to our knowledge is the first time this has been accomplished for the lattice energy of any organic crystal.
2. How do substituents tune pi-pi interactions? Here we wish to know the basic rules of the game, which could be used in rational design of drugs or supramolecular architectures, or in crystal engineering. Building upon previous work in our laboratory, student Steve Arnstein has been pursuing potential energy curves of substituted benzene dimers in parallel-displaced (slipped parallel) configurations. Summer student Ed Hohenstein has also been examining heteroatom effects by looking at pyridine dimer and the benzene-pyridine complex.
3. Potential energy surfaces for pi-pi interactions. We are concerned not only with the minimum-energy configurations of pi-pi interactions, but also the general features of their potential energy surfaces. This is important because in actual, complex systems, the fundamental noncovalent interactions may not be able to achieve their "optimal" geometric configurations that would be observed in smaller gas phase complexes due to steric constraints or secondary interactions. In our work on substituted and heteroatom derivatives, and on approximate methods below, we have examined not just minima, but entire potential curves.
4. Additivity of pi-pi interactions. We are also interested in how pi-pi interactions may be adjusted or polarized based on other nearby chemical groups (such as another pi system). We have published a study on benzene trimers and tetramers, and we have carefully examined the effect of three-body effects in our computations of crystalline benzene discussed above.
5. Testing approximate models for pi-pi and other noncovalent interactions. Recognizing that large-basis CCSD(T) computations are very hard to extend to larger systems, we have also been searching for approximate methods which might be applicable to larger systems while still yielding results close to our benchmark results. In one paper by Tait Takatani (submitted to Phys. Chem. Chem. Phys.), we examine Grimme's spin-component-scaled MP2 approach and related methods. We also consider the effect of local correlation approximations, which we find work well in general, but have surprising difficulties for the aug-cc-pVDZ basis set. Ongoing work also considers force-field methods as even less computationally expensive alternatives.
