Substituent Effects on the Hydrogen Bonding Between Phenolate and HF, H2O and NH3

IntroductionSubstituent effects have been well known forthe covalently bonded systems for many years,they have found tremendous applications in medicalchemistry,biochemistry,organic chemistry,andmaterial chemistry[1] . In fact,the studies ofsubstituent effects have greatly contributed to ourunderstanding of chemical mechanisms,and theestablishments of many chemical theories haveheavily relied on the observed substituent effects.However,it turns out that little have beenknown so far the substit…     

A comparison of the role of charge transfer,hyperconjugation, inductive and field interactions in substitutd methyl and silyl substituent effects on benzene π vertical ionization energies

The first two vertical π-ionization energies of MX₃ substituted benzenes as determined by photoelectron spectroscopy are compared with the results of modified CNDO/2 calculations, where M is Si or C and X is H, F, Cl and OCH₃. The major substituent interaction mechanisms of MX₃ are described within the CNDO/2 model. The results for methylorthobenzoate support intramolecular charge transfer stabilization of the benzene radical cation ground state by oxygen lone pair electrons, whereas the dominant interaction of the Si(OCH₃)₃ group is a positive charge stabilising field effect. The first vertical ionization energies of PhSiCl₃ and PhCCl₃ are unexpectedly assigned to ionization from the a′ π orbital rather than the a″ orbital nodal at the substituent site. Carbon-chlorine hyperconjugation is a suggested stabilizing interaction in the PhCCl₃²A′ cation. The shape of the first band in the PE spectrum of phenylsilane is described as a possible example of a pseudo Jahn—Teller effect. Unlike CX₃, SiX₃ substituents except, where X is methoxy, exhibit calculated opposing field and σ-inductive effects.     

Remote substituent effects on N-X (X = H,F, Cl,CH3, Li) bond dissociation energies in para-substituted anilines

UB3LYP/6-311++g**//UB3LYP/6-31+g* and ROMP2/6-311++g**//UB3LYP/6-31+g* methods were used to calculate (i) N-X bond dissociation energies (BDE) in 4-YC6H4NH-X and (ii) N-H BDEs in 4-YC6H4NU-H, where Y = H, Me, OCH3, SMe, NH2, NMe2, SiMe3, F, Cl, CN, COOH, CF3, and NO2, X = H, CH3, F, Cl, and Li, and U = H, F, and CH(3). It was found that N-H BDEs of 4-YC6H4NH2 have a positive correlation with the substituent sigma(p+) constants. The slope (rho+) is about 3.0-4.3 kcal/mol, which is in good agreement with the experimental results. It was also found that the substituent effects on N-X BDEs of 4-YC6H4NH-X change considerably when X changes. rho(+)values for N-CH3, N-F, N-Cl, and N-Li BDEs were calculated to be 3.1-4.6, 1.3-1.9, 1.8-2.6, and 4.9-6.8 kcal/mol, respectively. The reason for the variation of substituent effects was proposed to be the ground-state effect, i.e., the interaction between the intact NH-X moiety and the parasubstituents. Finally, alpha-substitution was found to be able to significantly change the substituent effects. rho(+)values for N-H BDEs of 4-C6H4NCH3(-)H and 4-C6H4NF-H are 2.5-4.0 and 1.7-1.9 kcal/mol, respectively.     

Theoretical ab initio study of the interplay between hydrogen bonding, cation–π and π–π interactions

The interplay among three important non-covalent interactions involving aromatic rings is studied by means of ab initio calculations (RI-MP2/aug-cc-pVTZ//RI-MP2/aug-cc-pVDZ, and RI-MP2/CBS levels of theory). They demonstrate that synergetic effects are present in complexes where hydrogen bonding interactions, cation–π, and π–π interactions coexist. These synergetic effects have been studied using the genuine non-additivity energies and the molecular interaction potential with polarization partition scheme.     

On the Role of Charge Transfer in Many-Body Non-Covalent Interactions**

Charge transfer is one of the mechanisms involved in non-covalent interactions. In molecular dimers, its contribution to pairwise interaction energies has been studied extensively using a variety of interaction energy decomposition schemes. In polar interactions such as hydrogen bonds, it can contribute ten or several tens of percent of the interaction energy. Less is known about its importance in higher-order interactions in many-body systems, mainly because of the lack of methods applicable to this problem. In this work, we extend our method for the quantification of the charge-transfer energy based on constrained DFT to many-body cases and apply it to model trimers extracted from molecular crystals. Our calculations show that charge transfer can account for a large fraction of the total three-body interaction energy. This also has implications for DFT calculations of many-body interactions in general as it is known that many DFT functionals struggle to describe charge-transfer effects correctly.     

How Can Rotaxanes Be Modified by Varying Functional Groups at the Axle?—A Combined Theoretical and Experimental Analysis of Thermochemistry and Electronic Effects

We present theoretically as well as experimentally determined thermochemical data of the non-covalent interactions in different axle-substituted pseudorotaxanes. The overall interaction energy lies in the region of 35 kJ mol(-1), independent of the substitution pattern at the axle. Because rearrangement energies of 7 and 3 kJ mol(-1) are required for wheel and axle, respectively, the sum of the net interactions of individual non-covalent bonds must exceed 10 kJ mol(-1) to achieve a successful host-guest interaction. The geometrical analysis shows three hydrogen bonds, and the close inspection of the individual dipole moments as well as the individual hydrogen bonds reveals trends according to the different functional groups at the axle. The individual trends for the different hydrogen bonds almost lead to a cancellation of the substitution effects. From solvent-effect considerations it can be predicted that the pseudorotaxane is stable in CHCl(3) and CH(2)Cl(2), whereas it would dethread in water. Comparing experimentally and theoretically calculated Gibbs free enthalpies, we find reasonable agreement if an exchange reaction of one solvent molecule instead of the direct formation reaction is considered.     

The performance of ANI-ML potentials for ligand-n(H2O) interaction energies and estimation of hydration free energies from end-point MD simulations

Here, we investigate the performance of “Accurate NeurAl networK engINe for Molecular Energies” (ANI), trained on small organic compounds, on bulk systems including non-covalent interactions and applicability to estimate solvation (hydration) free energies using the interaction between the ligand and explicit solvent (water) from single-step MD simulations. The method is adopted from ANI using the Atomic Simulation Environment (ASE) and predicts the non-covalent interaction energies at the accuracy of wb97x/6-31G(d) level by a simple linear scaling for the conformations sampled by molecular dynamics (MD) simulations of ligand-n(H₂O) systems. For the first time, we test ANI potentials' abilities to reproduce solvation free energies using linear interaction energy (LIE) formulism by modifying the original LIE equation. Our results on ~250 different complexes show that the method can be accurate and have a correlation of R² = 0.88–0.89 (MAE <1.0 kcal/mol) to the experimental solvation free energies, outperforming current end-state methods. Moreover, it is competitive to other conventional free energy methods such as FEP and BAR with 15-20 × fold reduced computational cost.     

Ab initio study of 4-monosubstituted pyrimidines in ground and excited n → π* states

Ab initio SCF and SCF -CI calculations have been performed to investigate substituent effects on ground- and excited-state properties of 4-R-pyrimidines, and to compare these with substituent effects in 2- and 4-R-pyridines, with R including the π donating and σ withdrawing groups CH₃, NH₂, OH, F, and C₂H₃ and the σ and π electron-withdrawing groups CHO and CN. Substitution leads to significant changes in the internal angles of the pyrimidine ring, which are independent of the nature of the substituent. The geometry of the pyrimidine ring is more sensitive to substitution in the 4 position than the pyridine ring geometry is to substitution in either the 2 or the 4 position. The isodesmic reaction energies for substituent transfer from the 4 position of pyrimidine to the 2 or 4 position of pyridine indicate that all R groups except CN have a relative stabilizing effect in pyrimidine. The presence of a π donating group leads to an increase in the n→π* transition energy of 4-R-pyrimidines, while the π withdrawing group CN leads to a decrease in the transition energy relative to pyrimidine. Orbital energy differences and virtual excitation energies tend to correlate with n→π* transition energies of 4-R-pyrimidines with saturated R groups, but such correlations are masked by π conjugation, n orbital interaction, and configurational mixing when the unsaturated groups C₂H₃, CHO, and CN are present. The electronic effects of a π donating group are stronger when the group is bonded to pyrimidine than to pyridine, but those of a π withdrawing group are weaker when the group is bonded to pyrimidine.     

Theoretical Study of Remote Substituent Effects on X-H （X=CH2, NH,O） Bond Dissociation Energies of Azulene

In the study, the X-H （X=CH2, NH, O） bond dissociation energies （BDE） of para-substituted azulene （Y-C10H8X-H） were predicted theoretically for the first time using Density Functronal Theory （DFT） methods at UB3LYP/6-311 ＋ ＋g（2df,2p）//UB3LYP/6-31 ＋g（d） level. It was found that the substituents exerted similar effects on the X-H BDE of azulene as those on benzene, except for 6-substituted 2-methylazulene. Owing to the substituent-dipole interaction, the reaction constants （ρ^＋） of 2- and 6-Y-CIoHsX-H （X=NH and O only） varied violently. The origin of the substituent effects on the X-H BDE of azulene was found, by both GE/RE and SIE theory, to be directly associated with variation of the radical effects, although the ground effects also played a modest role in determining the net. substituent effects.     

Parameterization of a B3LYP specific correction for non-covalent interactions and basis set superposition error on a gigantic dataset of CCSD(T) quality non-covalent interaction energies

A vast number of non-covalent interaction energies at the counterpoise corrected CCSD(T) level have been collected from the literature to build a diverse new dataset. The whole dataset, which consists of 2027 CCSD(T) energies, includes most of the published data at this level. A large subset of the data was then used to train a novel, B3LYP specific, empirical correction scheme for non-covalent interactions and basis set superposition error (abbreviated as B3LYP-MM). Results obtained with our new correction scheme were directly compared to benchmark results obtained with B3LYP-D3(1) and M06-2X(2) (two popular density functions designed specifically to accurately model non-covalent interactions). For non-covalent complexes dominated by dispersion or dipole-dipole interactions all three tested methods give accurate results with the medium size aug-cc-pVDZ(3-6) basis set with MUE's of 0.27 (B3LYP-MM), 0.32 (B3LYP-D3) and 0.47 kcal/mol (M06-2X) (with explicit counterpoise corrections). These results validate both B3LYP-D3 and M06-2X for interactions of this type using a much larger data set than was presented in prior work. However, our new dispersion correction scheme shows some clear advantages for dispersion and dipole-dipole dominated complexes with the small LACVP* basis set, which is very popular in use due to its low associated computational cost: The MUE for B3LYP-MM with the LACVP* basis set for this subset of complexes (without explicit counterpoise corrections) is only 0.28 kcal/mol, compared to 0.65 kcal/mol for M06-2X or 1.16 kcal/mol for B3LYP-D3. Additionally, our new correction scheme also shows major improvements in accuracy for hydrogen-bonded systems and for systems involving ionic interactions, for example cation-π interactions. Compared to B3LYP-D3 and M06-2X, we also find that our new B3LYP-MM correction scheme gives results of higher or equal accuracy for a large dataset of conformer energies of di- and tripeptides, sugars, and cysteine.     

Effects of π bond type,backbone size,and halogen on structural and spectroscopic properties of hydrogen‐bonded complexes of the X?H … π type between alkenes or alkynes and haloacids (HF and HCl)

The effects of CC bond type (double or triple), substituent (H or methyl), and halogen (F and Cl) on three properties of hydrogen‐bonded complexes formed between unsaturated hydrocarbons and HX (X?F, Cl) are studied. The properties comprise hydrogen bond distances (R_H), stabilization energies (SE), and frequency shifts (Δν). A 2³ factorial design technique, along with ab initio (HF and MP2) and DFT (B3LYP and PBE1PBE) calculations, has been employed. All three responses are mainly affected by the halogen, and when it is changed from F to Cl, R_H tends to increase, while SE tends to decrease. Surprisingly, the type of substituent is more important than the type of CC bond, for all three responses. Both effects tend to decrease R_H. Significant interaction effects are obtained for the type of CC bond along with the type of substituent, and for the type of substituent along with the type of halogen. Both interaction effects are smaller than the main effects and also tend to decrease R_H. The greatest SE values are obtained with PBE1 functional (BSSE + ZPE corrected values). Again, the next more important effect is due to the type of substituent, and the replacement of H by CH₃ group tends to increase SE. The effect due to the CC bond type is not significant, at all computational levels. The only interaction effect that is significant for SE (corrected) and Δν is between factors 1 (CC bond type) and 2 (substituent), but only at HF and B3LYP levels, and it tends to increase both properties. As the halogen changes from F to Cl, Δν tends to decrease. In contrast, changing the substituent from H to CH₃ leads to greater values of Δν. The effect of CC bond type is not significant at HF level, and when it is changed from double to triple Δν is decreased, at B3LYP and PBE1 levels. A suggestion as to how the results may point toward a better experimental detection of similar (π‐type) complexes is also given. © 2005 Wiley Periodicals, Inc. Int J Quantum Chem, 2006     

Are calculated enthalpies of formation sometimes more reliable than experimental? A test on alkyl substituted benzoic acids

Energies of 20 alkyl-substituted benzoic acids were calculated at the levels B3LYP/6-311+G(d,p)//B3LYP/6-311+G(d,p) and MP2/6-311+G(d,p)//MP2/6-311+G(d,p); the pertinent enthalpies at 298 K were calculated at the same levels. Comparison with experimental enthalpies of formation Delta(f)H degrees (g)(298) was carried out in terms of isodesmic reactions, that is, in the relative values. Of the four calculated quantities, the DFT enthalpies yielded best correlation with the standard deviation of 2.1 kJ mol(-1), near to the experimental uncertainty; the DFT energies are only slightly worse and the MP2 enthalpies or energies much worse. However, the DFT method overestimated systematically the substituent effects and had to be calibrated. Comparison with the experimental gas-phase acidities was less telling and the fit was worse because both methods overestimated the substituent effects. Extending the base in selected examples did not give better results. Although the systematic deviations are evidently due to the imperfections of the theoretical models, individual big deviations should be attributed to experimental errors or to the abnormal behavior of certain compounds at the experimental conditions. From this point of view, three examples of the so-called long-range effect claimed in the case of different benzoic acid derivatives, always for substituents in the meta position, must be refused as unproven because the experimental energies were not confirmed by calculations.     

The nido-Cage⋅⋅⋅π Bond: A Non-covalent Interaction between Boron Clusters and Aromatic Rings and Its Applications

Non-covalent interactions involving multicenter multielectron skeletons such as boron clusters are rare. Now, a non-covalent interaction, the nido-cage⋅⋅⋅π bond, is discovered based on the boron cluster C₂B₉H₁₂⁻ and an aromatic π system. The X-ray diffraction studies indicate that the nido-cage⋅⋅⋅π bonding presents parallel-displaced or T-shaped geometries. The contacting distance between cage and π ring varies with the type and the substituent of the aromatic ring. Theoretical calculations reveal that this nido-cage⋅⋅⋅π bond shares a similar nature to the conventional anion⋅⋅⋅π or π⋅⋅⋅π bonds found in classical aromatic ring systems. This nido-cage⋅⋅⋅π interaction induces variable photophysical properties such as aggregation-induced emission and aggregation-caused quenching in one molecule. This work offers an overall understanding towards the boron cluster-based non-covalent bond and opens a door to investigate its properties.     

Benchmarking density functional methods against the S66 and S66x8 datasets for non-covalent interactions

Dispersion-corrected density functional theory is assessed on the new S66 and S66x8 benchmark sets for non-covalent interactions. In total, 17 different density functionals are evaluated. Two flavors of our latest additive London-dispersion correction DFT-D3 and DFT-D3(BJ), which differ in their short-range damping functions, are tested. In general, dispersion corrections are again shown to be crucial to obtain reliable non-covalent interaction energies and equilibrium distances. The corrections strongly diminish the performance differences between the functionals, and in summary most dispersion-corrected methods can be recommended. DFT-D3 and DFT-D3(BJ) also yield similar results but for most functionals and intermolecular distances, the rational Becke-Johnson scheme performs slightly better. Particularly, the statistical analysis for S66x8, which covers also non-equilibrium complex geometries, shows that the Minnesota class of functionals is also improved by the D3 scheme. The best methods on the (meta-)GGA or hybrid- (meta-)GGA level are B97-D3, BLYP-D3(BJ), PW6B95-D3, MPW1B95-D3 and LC-ωPBE-D3. Double-hybrid functionals are the most accurate and robust methods, and in particular PWPB95-D3 and B2-PLYP-D3(BJ) can be recommended. The best DFT-D3 and DFT-D3(BJ) approaches are competitive to specially adapted perturbation methods and clearly outperform standard MP2. Comparisons between S66, S22 and parts of the GMTKN30 database show that the S66 set provides statistically well-behaved data and can serve as a valuable tool for, for example, fitting purposes or cross-validation of other benchmark databases.     

Double-hybrid density functionals with long-range dispersion corrections: higher accuracy and extended applicability

The objective of this work is the further systematic improvement of the accuracy of Double-Hybrid Density Functionals (DHDF) that add non-local electron correlation effects to a standard hybrid functional by second-order perturbation theory (S. Grimme, J. Chem. Phys., 2006, 124, 034108). The only known shortcoming of these generally highly accurate functionals is an underestimation of the long-range dispersion (van der Waals) interactions. To correct this deficiency, we add a previously developed empirical dispersion term (DFT-D) to the energy expression but leave the electronic part of the functional untouched. Results are presented for the S22 set of non-covalent interaction energies, the G3/99 set of heat of formations and conformational energies of a phenylalanyl-glycyl-glycine peptide model. We furthermore propose seven hydrocarbon reactions with strong intramolecular dispersion contributions as a benchmark set for newly developed density functionals. In general, the proposed composite approach is for many chemically relevant properties of similar quality as high-level coupled-cluster treatments. A significant increase of the accuracy for non-covalent interactions is obtained and the corrected B2PLYP DHDF provides one of the lowest ever obtained Mean Absolute Deviations (MAD) for the S22 set (0.2-0.3 kcal mol(-1)). Unprecedented high accuracy is also obtained for the relative energies of peptide conformations that turn out to be very difficult. The significant improvements found for the G3/99 set (reduction of the MAD from 2.4 to 1.7 kcal mol(-1)) underline the importance of intramolecular dispersion effects in large molecules. In all tested cases the results from the standard B3LYP approach are also significantly improved, and we recommend the general use of dispersion corrections in DFT treatments.     

Theoretical study on the interactions of halogen‐bonds and pnicogen‐bonds in phosphine derivatives with Br2, BrCl,and BrF

The MP2 ab initio quantum chemistry methods were utilized to study the halogen‐bond and pnicogen‐bond system formed between PH₂X (X = Br, CH₃, OH, CN, NO₂, CF₃) and BrY (Y = Br, Cl, F). Calculated results show that all substituent can form halogen‐bond complexes while part substituent can form pnicogen‐bond complexes. Traditional, chlorine‐shared and ion‐pair halogen‐bonds complexes have been found with the different substituent X and Y. The halogen‐bonds are stronger than the related pnicogen‐bonds. For halogen‐bonds, strongly electronegative substituents which are connected to the Lewis acid can strengthen the bonds and significantly influenced the structures and properties of the compounds. In contrast, the substituents which connected to the Lewis bases can produce opposite effects. The interaction energies of halogen‐bonds are 2.56 to 32.06 kcal·mol^?1; The strongest halogen‐bond was found in the complex of PH₂OH???BrF. The interaction energies of pnicogen‐bonds are in the range 1.20 to 2.28 kcal·mol^?1; the strongest pnicogen‐bond was found in PH₂Br???Br₂ complex. The charge transfer of lp(P) ? σ*(Br? Y), lp(F) ? σ*(Br? P), and lp(Br) ? σ*(X? P) play important roles in the formation of the halogen‐bonds and pnicogen‐bonds, which lead to polarization of the monomers. The polarization caused by the halogen‐bond is more obvious than that by the pnicogen‐bond, resulting in that some halogen‐bonds having little covalent character. The symmetry adapted perturbation theory (SAPT) energy decomposition analysis showes that the halogen‐bond and pnicogen‐bond interactions are predominantly electrostatic and dispersion, respectively.     

Strength and Nature of Host-Guest Interactions in Metal-Organic Frameworks from a Quantum-Chemical Perspective

Metal-organic frameworks (MOFs) offer a convenient means for capturing, transporting, and releasing small molecules. Their rational design requires an in-depth understanding of the underlying non-covalent host-guest interactions, and the ability to easily and rapidly pre-screen candidate architectures in silico. In this work, we devised a recipe for computing the strength and analysing the nature of the host-guest interactions in MOFs. By assessing a range of density functional theory methods across periodic and finite supramolecular cluster scale we find that appropriately constructed clusters readily reproduce the key interactions occurring in periodic models at a fraction of the computational cost. Host-guest interaction energies can be reliably computed with dispersion-corrected density functional theory methods; however, decoding their precise nature demands insights from energy decomposition schemes and quantum-chemical tools for bonding analysis such as the quantum theory of atoms in molecules, the non-covalent interactions index or the density overlap regions indicator.     

Molecular orbital theory of the hydrogen bond. 27. Substituent effects in water: 4-R-pyrimidine complexes

Ab initio SCF calculations with the STO -3G basis set have been performed to investigate substituent effects on the structures and stabilization energies of water:4-R-pyrimidine complexes, with R including CH₃, NH₂, OH, F, C₂H₃, CHO, and CN. Except for the cyclic water:4-aminopyrimidine complex hydrogen bonded at N₃, these complexes have open structures stabilized by a nearly linear hydrogen bond formed through a nitrogen lone pair of electrons. When hydrogen bonding occurs at N₃, the complexes may have planar or perpendicular conformations depending on the substituent, but when hydrogen bonding occurs at N₁, the perpendicular is generally slightly preferred, and there is essentially free rotation of the 4-R-pyrimidine. Primary substituent effects alter the electronic environment at the nitrogens, and tend to make N₃ a poorer site for hydrogen bonding than N₁, primarily because of a stronger π electron-withdrawing effect at N₃. However, the relative stabilities of complexes hydrogen bonded at N₁ and N₃ are also influenced by secondary substituent effects, which may be significant in stabilizing complexes bonded at N₃. Substitutent effects on the structures and stabilization energies of the water:4-R-pyrimidine complexes are similar to substitutent effects in water:2-R-pyridine and water:4-R-pyrimidine complexes are similar to substitutent effects in water:2-R-pyridine and water:4-R-pyridine complexes. Configuration interaction calculations indicate that although absorption of energy by the pyrimidine ring destabilizes the water:4-R-pyrimidine complexes, these may still remain bound in the excited n → π* state. This is in contrast to the fate of open water:2-R-pyridine and water:4-R-pyridine complexes, which dissociate in this state.     

Theoretical Study of the N-NO2 Bond Dissociation Energies for Energetic Materials with Density Functional Theory

The N-NO2 bond dissociation energies （BDEs） for 7 energetic materials were computed by means of accurate density functional theory （B3LYP, B3PW91 and B3P86） with 6-31G＊＊ and 6-311G＊＊ basis sets. By comparing the computed energies and experimental results, we find that the B3P86/6-311G＊＊ method can give good results of BDE, which has the mean absolute deviation of 1.30kcal/mol. In addition, substituent effects were also taken into account. It is noted that the Hammett constants of substituent groups are related to the BDEs of the N-NO2 bond and the bond dissociation energies of the energetic materials studied decrease when increasing the number of NO2 group.     

Effect of substituents on the strength of N-X (X = H, F, and Cl) bond dissociation energies: a high-level quantum chemical study

The effect of substituents on the strength of N-X (X = H, F, and Cl) bonds has been investigated using the high-level W2w thermochemical protocol. The substituents have been selected to be representative of the key functional groups that are likely to be of biological, synthetic, or industrial importance for these systems. We interpreted the effects through the calculation of relative N-X bond dissociation energies (BDE) or radical stabilization energies (RSE(NX)). The BDE and RSE(NX) values depend on stabilizing/destabilizing effects in both the reactant molecule and the product radical of the dissociation reactions. To assist us in the analysis of the substituent effects, a number of additional thermochemical quantities have been introduced, including molecule stabilization energies (MSE(NX)). We find that the RSE(NH) values are (a) increased by electron-donating alkyl substituents or the vinyl substituent, (b) increased in imines, and (c) decreased by electron-withdrawing substituents such as CF(3) and carbonyl moieties or through protonation. A different picture emerges when considering the RSE(NF) and RSE(NCl) values because of the electronegativities of the halogen atoms. The RSE(NX)s differ from the RSE(NH) values by an amount related to the stabilization of the N-halogenated molecules and given by MSE(NX). We find that substituents that stabilize/destabilize the radicals also tend to stabilize/destabilize the N-halogenated molecules. As a result, N-F- and N-Cl-containing molecules that include alkyl substituents or correspond to imines are generally associated with RSE(NF) and RSE(NCl) values that are less positive or more negative than the corresponding RSE(NH). In contrast, N-F- and N-Cl-containing molecules that include electron-withdrawing substituents or are protonated are generally associated with RSE(NF) and RSE(NCl) values that are more positive or less negative than the corresponding RSE(NH).