Cation-π interaction: its role and relevance in chemistry, biology, and material science.

With both catalytic and genetic functions, ribonucleic acid (RNA) is perhaps the most pluripotent chemical species in molecular biology, and its functions are intimately linked to its structure and dynamics. Computer simulations, and in particular atomistic molecular dynamics (MD), allow structural dynamics of biomolecular systems to be investigated with unprecedented temporal and spatial resolution. We here provide a comprehensive overview of the fast-developing field of MD simulations of RNA molecules. We begin with an in-depth, evaluatory coverage of the most fundamental methodological challenges that set the basis for the future development of the field, in particular, the current developments and inherent physical limitations of the atomistic force fields and the recent advances in a broad spectrum of enhanced sampling methods. We also survey the closely related field of coarse-grained modeling of RNA systems. After dealing with the methodological aspects, we provide an exhaustive overview of the ava...

RNA Structural Dynamics As Captured by Molecular Simulations: A Comprehensive Overview.

What are the pKa values of C–H bonds in aromatic heterocyclic compounds in DMSO?

Ab initio (HF, MP2, and CCSD(T)) and DFT (B3LYP) calculations were done in modeling the cation (H(+), Li(+), Na(+), K(+), Ca(2+), Mg(2+), NH(4)(+), and NMe(4)(+)) interaction with aromatic side chain motifs of four amino acids (viz., phenylalanine, tyrosine, tryptophan and histidine). As the metal ion approaches the pi-framework of the model systems, they form strongly bound cation-pi complexes, where the metal ion is symmetrically disposed with respect to all ring atoms. In contrast, proton prefers to bind covalently to one of the ring carbons. The NH(4)(+) and NMe(4)(+) ions have shown N-H...pi interaction and C-H...pi interaction with the aromatic motifs. The interaction energies of N-H...pi and C-H...pi complexes are higher than hydrogen bonding interactions; thus, the orientation of aromatic side chains in protein is effected in the presence of ammonium ions. However, the regioselectivity of metal ion complexation is controlled by the affinity of the site of attack. In the imidazole unit of histidine the ring nitrogen has much higher metal ion (as well as proton) affinity as compared to the pi-face, facilitating the in-plane complexation of the metal ions. The interaction energies increase in the order of 1-M Ca(2+) > Li(+) > Na(+) > K(+) congruent with NH(4)(+) > NMe(4)(+). The variation of the bond lengths and the extent of charge transfer upon complexation correlate well with the computed interaction energies.

Cation [M = H+, Li+, Na+, K+, Ca2+, Mg2+, NH4+, and NMe4+] interactions with the aromatic motifs of naturally occurring amino acids: a theoretical study.

Composite ab initio CBS-Q and G3 methods were used to calculate the bond dissociation energies (BDEs) of over 200 compounds listed in CRC Handbook of Chemistry and Physics (2002 ed.). It was found that these two methods agree with each other excellently in the calculation of BDEs, and they can predict BDEs within 10 kJ/mol of the experimental values. Using these two methods, it was found that among the examined compounds 161 experimental BDEs are valid because the standard deviation between the experimental and theoretical values for them is only 8.6 kJ/mol. Nevertheless, 40 BDEs listed in the Handbook may be highly inaccurate as the experimental and theoretical values for them differ by over 20 kJ/mol. Furthermore, 11 BDEs listed in the Handbook may be seriously flawed as the experimental and theoretical values for them differ by over 40 kJ/mol. Using the 161 cautiously validated experimental BDEs, we then assessed the performances of the standard density functional (DFT) methods including B3LYP, B3P86, ...

Assessment of experimental bond dissociation energies using composite ab initio methods and evaluation of the performances of density functional methods in the calculation of bond dissociation energies.

UB3LYP/6-31G(d) and ROMP2/6-311++G(d,2p) methods were used to calculate the Si-X bond dissociation energies (BDEs) of a number of para-substituted aromatic silanes (4-Y-C(6)H(4)-SiH(2)X, where X = H, F, Cl, or Li). It was found that the substituent effect on the Si-H BDE of 4-Y-C(6)H(4)-SiH(3) was small, as the slope (rho(+)()) of the BDE- regression was only 0.09 kJ/mol. In comparison, the substituent effect on the Si-F BDE of 4-Y-C(6)H(4)-SiH(2)F was much stronger, whose rho(+ )()value was -2.34 kJ/mol. The substituent effect on the Si-Cl BDE of 4-Y-C(6)H(4)-SiH(2)Cl was also found to be strong with a rho(+)() value of -1.70 kJ/mol. However, the substituent effect on the Si-Li BDE of 4-Y-C(6)H(4)-SiH(2)Li was found to have a large and positive slope (+9.12 kJ/mol) against. The origin of the above remarkably different substituent effects on the Si-X BDEs was found to be associated with the ability of the substituent to stabilize or destabilize the starting material (4-Y-C(6)H(4)-SiH(2)X) as well as the product (4-Y-C(6)H(4)-SiH(2)* radical) of the homolysis. Therefore, the direction and magnitude of the effects of Y-substituents on the Z-X BDEs in compounds such as 4-YC(6)H(4)Z-X should have some important dependence on the polarity of the Z-X bond undergoing homolysis. This conclusion was in agreement with that from earlier studies (for example, J. Am. Chem. Soc. 1991, 113, 9363). However, it indicated that the proposal from a recent work (J. Am. Chem. Soc. 2001, 123, 5518) was unfortunately not justified.

Remote substituent effects on bond dissociation energies of para-substituted aromatic silanes.

In the study we tried to answer two questions. First, does X-Z homolytic bond dissociation energy (BDE) of Y-C6H4-X-Z obey the Hammett relationship? Second, if it does what factors determine the ma...

Remote substituent effects on homolytic bond dissociation energies.

The performances of a number of theoretical methods in the calculation of N-H bond dissociation energies and radical stabilization energies associated with the X-NH° radicals were examined. It was found that the UHF, UMP2, and UMP4 methods were not reliable for the nitrogen radicals because of the spin contamination suffered by them. Surprisingly, the ROHF, ROMP2, and ROB3LYP methods were not found to be reliable for the nitrogen radicals either, because they could lead to unrealistic spin-localization of the radical. This unrealistic spin-localization was even seen with the UCCSD(T) method. The only credible modest-level method for the nitrogen radical was found to be UB3LYP, which could provide at least qualitatively correct radical stabilization energies for the nitrogen radicals. The basis set effect on the UB3LYP calculation was also found to be very small. Nevertheless, G3 and CBS-Q methods were found to be able to provide fairly accurate bond dissociation energies and radical stabilization energies for the substituted nitrogen radicals. According to G3 and CBS-Q results, CH 3 , NH 2 , OH, F, Cl, and CN were assigned to be stabilizing substituents for the nitrogen radical, as these groups could effectively delocalize the odd electron on the nitrogen radical. By contrast, COCH 3 , CONH 2 , COOH, and CHO were assigned to be destabilizing substituents for the nitrogen radical, although these groups could also delocalize the odd electron on the nitrogen radical. The origin of the destabilization effect was found to be the loss of the conjugation between the NH 2 lone-pair electrons and the substituent from the neutral X-NH 2 molecule to the X-NH° radical.

Radical Stabilization Energies of Substituted XNH¥ Radicals

Systematic theoretical calculations were performed on the interactions between benzene and a variety of MX+ cations (M = Be2+, Mg2+, and Ca2+; X = H-, F-, Cl-, OH-, SH-, CN-, NH2-, and CH3-) in order to expand the scope of the cation−π interaction. It was found that the basis set and electron correlation effects on the geometry optimization and energy calculation were small. Therefore, the chosen method of this study, MP2/6-311++g(2d,2p)//MP2/6-31+g*, should be sufficiently reliable. Using this method, it was found that the cation−π interaction between benzene and a naked alkaline earth cation is much stronger than the prototypical benzene−alkali cation interaction. In comparison, when a counterion is introduced into the complex, the C6H6...MX+ interaction is very similar to the benzene−alkali cation in many aspects. Further analyses indicated that electrostatic interaction is the major driving force for C6H6...Li+ and C6H6...Na+ complexes, whereas large charge transfer occurs in C6H6...Be2+ and C6H6...Mg...

Counterion effects on the cation-π interaction between alkaline earth cations and benzene

The P–X (X = H, F, and Cl) bond dissociation energies (BDEs) for a number of para- and meta-substituted aromatic phosphines were calculated using R(O)MP2/6-311++g(d, 2p)//(U)B3LYP/6-31g(d) method. The results showed the importance of the radical effect as well as the ground effect on the BDEs. For X = H case, because the substituent affected the neutral phosphine to the same extent as it affected the radical, substituent effects on the P–H BDE were small (ρ+ = 0.28 kJ/mol). In comparison, for X = F or Cl case, because the substituent affected the neutral phosphine much more strongly than it affected the radical, substituent effects on the P–F (ρ+ = −3.25 kJ/mol) or P–Cl (ρ+ = −1.31 kJ/mol) BDEs were significant. Therefore, the substituent effects on BDEs of the Z–X bonds in compounds of the general formula 4-YC6H4Z–X varied when X changed, which meant that a recent proposal (J. Am. Chem. Soc., 123, 5518 (2001)) was unfortunately not supported.

Yu-Hui Cheng

Papers

Remote substituent effects on bond dissociation energies of para-substituted aromatic silanes.

Remote substituent effects on homolytic bond dissociation energies.

Radical Stabilization Energies of Substituted XNH¥ Radicals

Counterion effects on the cation-π interaction between alkaline earth cations and benzene

A Theoretical Study of the Substituent Effects on the P–X (X = H, F, Cl) Bond Dissociation Energies in para- and meta-Substituted Aromatic Phosphines