Functional group corrections to the GFN2-xTB and PM6 semiempirical methods for noncovalent interactions in alkanes and alkenes.

Analytical corrections were developed to improve the accuracy of the PM6 and GFN2-xTB semiempirical quantum mechanical methods for the evaluation of noncovalent interaction energies in alkanes and alkenes. We followed the approach of functional group corrections, wherein the atom-atom pair corrections depend on the nature of the interacting functional groups. The training set includes 21 alkane and 13 alkene complexes taken from the Donchev et al.'s database [Sci. Data 8, 55 (2021)], with interaction energies calculated at the CCSD(T)/CBS level, and our own data obtained for medium-size complexes (of 100 and 112 atoms). In general, for the systems included in the training and validation sets, the errors obtained with the PM6-FGC and xTB-FGC methods are within the chemical accuracy.

Electrostatic penetration effects stand at the heart of aromatic π interactions.

The nature of the interaction in benzene-containing dimers has been analysed by means of Symmetry Adapted Perturbation Theory (SAPT). The total interaction energy and the preference for the dimers to adopt slipped structures are, apparently, consequence of the balance between repulsion and dispersion. However, our results indicate that this only holds when trends are analysed using fixed intermolecular distances. Employing the most favourable separations between rings it turns out that the changes on the total interaction energy are mostly controlled by electrostatics, while repulsion and dispersion cancel each other to a great extent. Most of the electrostatic contribution is accounted for by electrostatic penetration, so a description based on multipoles should not be employed to rationalise the interaction in benzene-containing dimers. The changes on the interaction energy in benzene-containing dimers are steered by electrostatic penetration which, though often overlooked, plays an essential role for the description of aromatic π interactions.

The PM6-FGC Method: Improved Corrections for Amines and Amides.

Recently, we reported a new approach to develop pairwise analytical corrections to improve the description of noncovalent interactions, by approximate methods of electronic structures, such as semiempirical quantum mechanical (SQM) methods. In particular, and as a proof of concept, we used the PM6 Hamiltonian and we named the method PM6-FGC, where the FGC acronym, corresponding to Functional Group Corrections, emphasizes the idea that the corrections work for specific functional groups rather than for individual atom pairs. The analytical corrections were derived from fits to B3LYP-D3/def2-TZVP (reference). PM6 interaction energy differences, evaluated for a reduced set of small bimolecular complexes, were chosen as representatives of saturated hydrocarbons, carboxylic, amine and, tentatively, amide functional groups. For the validation, the method was applied to several complexes of well-known databases, as well as to complexes of diglycine and dialanine, assuming the transferability of amine group corrections to amide groups. The PM6-FGC method showed great potential but revealed significant inaccuracies for the description of some interactions involving the -NH2 group in amines and amides, caused by the inadequate selection of the model compound used to represent these functional groups (an NH3 molecule). In this work, methylamine and acetamide are used as representatives of amine and amide groups, respectively. This new selection leads to significant improvements in the calculation of noncovalent interactions in the validation set.

Papel del aumento de la rigidez arterial central en el daño macro y microvascular en pacientes con enfermedad coronaria / Role of increased central arterial stiffness in macro and microvascular damage in patients with coronary artery disease

Antecedentes: Con frecuencia, los pacientes con cardiopatía tienen disfunción renal manifestada por el descenso del filtrado glomerular (FG) y/o aumento de la albuminuria. Objetivos: El objetivo fue estudiar el papel del aumento de la rigidez aórtica en la presencia y extensión de la enfermedad coronaria (EC) y en la disfunción renal en sujetos con EC. Pacientes y métodos: Estudio observacional transversal de 48 pacientes con sospecha de EC sometidos a coronariografía. Mediante tonometría de aplanamiento sobre la arterial radial y aplicando una función de transferencia, se calcularon los valores de presión arterial central. El estudio de la rigidez aórtica se hizo mediante la determinación de la velocidad de pulso carótida-femoral (Vpc-f). Resultados: De los 48 pacientes, 11 no tenían lesiones coronarias significativas, 24 evidenciaron lesiones significativas en una o dos arterias coronarias y 13 en ≥ tres arterias. El grupo con mayor grado de EC tenía valores de presión de pulso central (PPc) más altos que el grupo sin EC. La Vpc-f aumentaba de forma progresiva y significativa con el grado de EC. La regresión logística mostraba que la VPc-f predecía de forma independiente la presencia de EC. El FG se correlacionaba de forma negativa y significativa con la edad. La Vpc-f se asociaba a la albuminuria. Conclusiones: En pacientes con EC estable, la Vpc-f se relaciona de forma independiente con la existencia y extensión de la EC, así como con la disminución del FG y el aumento de la albuminuria.(AU)

Background: Patients with heart disease frequently have renal dysfunction manifested by a decrease in glomerular filtration rate (GFR) and / or increase of albuminuria. Objectives: The objective was to study the possible role of increased aortic stiffness in the presence and extent of coronary artery disease (CAD) and kidney dysfunction in a group of patients with suspected CAD. Patients and methods: We studied forty-eight patients undergoing coronariography for suspected coronary disease (CAD). Using applanation tonometry on the radial artery and applying a transfer function, central blood pressure values were calculated. The study of aortic stiffness was done by determining the carotid-femoral pulse velocity (Pvc-f). Results: Of the 48 patients, 11 had no significant coronary lesions, 24 showed significant lesions in 1 or 2 coronary arteries and 13 in ≥ 3 arteries. The group with a higher degree of CD had significantly higher cPP values than the group without CD. The Pvc-f increased progressively and significantly with the degree of CD. The logistic regression showed that Pvc-f independently predicted the presence of CD. The relative risk of CD increased 2.5 times for each meter of increase in Pvc-f. The GFR was negatively and significantly correlated with age and Pvc-f was associated with albuminuria. Conclusions: In patients with stable CD, Pvc-f, expression of aortic stiffness, is independently associated with the existence of CD and its degree of extension. The increase in arterial stiffness also participates in the decrease in GFR and in the increase in albuminuria.(AU)

Role of increased central arterial stiffness in macro and microvascular damage in patients with coronary artery disease. / Papel del aumento de la rigidez arterial central en el daño macro y microvascular en pacientes con enfermedad coronaria.

BACKGROUND: Patients with heart disease frequently have renal dysfunction manifested by a decrease in glomerular filtration rate (GFR) and / or increase of albuminuria. OBJECTIVES: The objective was to study the possible role of increased aortic stiffness in the presence and extent of coronary artery disease (CAD) and kidney dysfunction in a group of patients with suspected CAD. PATIENTS AND METHODS: We studied forty-eight patients undergoing coronariography for suspected coronary disease (CAD). Using applanation tonometry on the radial artery and applying a transfer function, central blood pressure values were calculated. The study of aortic stiffness was done by determining the carotid-femoral pulse velocity (Pvc-f). RESULTS: Of the 48 patients, 11 had no significant coronary lesions, 24 showed significant lesions in 1 or 2 coronary arteries and 13 in ≥ 3 arteries. The group with a higher degree of CD had significantly higher cPP values than the group without CD. The Pvc-f increased progressively and significantly with the degree of CD. The logistic regression showed that Pvc-f independently predicted the presence of CD. The relative risk of CD increased 2.5 times for each meter of increase in Pvc-f. The GFR was negatively and significantly correlated with age and Pvc-f was associated with albuminuria. CONCLUSIONS: In patients with stable CD, Pvc-f, expression of aortic stiffness, is independently associated with the existence of CD and its degree of extension. The increase in arterial stiffness also participates in the decrease in GFR and in the increase in albuminuria.

Prognostic value of aortic valve area normalized to body size in native aortic stenosis.

INTRODUCTION AND OBJECTIVES: Although guidelines recommend the use of a cutoff value of 0.60 cm2/m2 for aortic valve area (AVA) normalized to body surface area (BSA) for severe aortic stenosis, there is little evidence of its prognostic value. Our aim was to test the value of AVA normalized to body size for outcome prediction in aortic stenosis. METHODS: One-hundred and ninety patients with at least moderate aortic stenosis (AVA <1.50 cm2) were prospectively enrolled. AVA was normalized to BSA and height. The primary endpoint was cardiovascular death under medical management. A receiver operating characteristic curve was plotted to determine the best cutoff value for predicting cardiovascular death. RESULTS: An AVA/BSA cutoff value of 0.50 had a sensitivity of 96% and specificity of 51%. An AVA/height cutoff value of 0.49 showed a sensitivity of 96% and a specificity of 52%. During a mean follow-up of 247±190 days, there were 24 cardiovascular deaths, with higher cardiovascular mortality in patients with AVA/BSA <0.50 cm2/m2 (21% vs 2.5%, P <.001) and AVA/height <0.49 cm2/m (25% vs 12%, P <.001). Two-year survival was 95±5% in patients with AVA/BSA> 0.50 cm2/m2 and was 37±5% in patients with AVA/BSA <0.50 cm2/m2 (P <.001). Cardiovascular death risk was higher in patients with AVA/BSA <0.50 cm2/m2 (adjusted 10.9 [1.2-103.7], P=.037), but cardiovascular mortality was not significantly higher in multivariate analysis for patients with AVA/height <0.49 cm2/m (2.0 [0.6-6.0], P=.22). CONCLUSIONS: We could identify a subgroup of patients at high risk of cardiovascular death when they were medically treated. Consequently we recommend using an AVA/BSA cutoff value of 0.50 cm2/m2 to identify a subgroup of patients with higher cardiovascular risk.

Curvature and size effects hinder halogen bonds with extended π systems.

Curvature and size effects in halogen interactions with extended aromatic species have been evaluated, employing computational methods, in dimers formed by dihalogens Cl2, Br2 and I2 with both planar (coronene and circumcoronene) and curved (corannulene, sumanene and C60) aromatic systems. The main controlling factor in these interactions is dispersion, so they become stronger as the size of the halogen grows. The nature of the interaction with the halogen changes depending on the curvature and the extension of the aromatic system. As the aromatic species becomes larger, parallel stacked structures are favoured by dispersion increases over halogen bonded ones. Parallel dimers by the concave side are also favoured as the curvature of the aromatic species increases, while the effect is the opposite by the convex side. Overall, halogen bond interactions are not favoured for large planar or curved aromatic systems; only by the convex face of the most curved structures the dispersion contribution decreases enough so as to make halogen bonded structures competitive with parallel stacked ones.

The relative position of π-π interacting rings notably changes the nature of the substituent effect.

The substituent effect in monosubstituted benzene dimers mostly follows changes on electrostatics mainly controlled by the direct interaction of the substituent and the other phenyl ring, whereas the contribution from the interacting rings is smaller. As the substituent is located further away the two contributions become of similar magnitude, so the global result is a combination of both effects. These trends are confirmed in larger systems containing a contact between phenyl rings; at closer distances the interaction of the substituent and the other ring clearly dominates over changes associated with the substituted ring, but as the substituent is located further away its contribution decreases and the contribution from the ring becomes more relevant. Care should be taken in larger systems because the observed energy change can also be affected by interactions with other regions of the molecule not directly involved in the π-π interaction.

Endohedral alkali cations promote charge transfer transitions in complexes of C60 with [10]cycloparaphenylenes.

[10]cycloparaphenylene ([10]CPP) effectively encapsulates ionic endofullerenes M+C60 (M = Li+, Na+, K+) as revealed by dispersion-corrected density functional theory methods. The interaction between [10]CPP and these fullerenes is dominated by dispersion, though it is stronger than with pristine C60 due to a reinforcement of electrostatic and induction contributions to the stability. The C60 carbon cage effectively shields the cations and distributes the charge among all carbon atoms, so the nature of the endohedral cation has no noticeable effect upon the final stability of the complexes. However, the presence of the cation induces important changes in the absorption spectra of the complexes, and new absorption bands near the infrared region appear. These bands are associated with charge transfer transitions from [10]CPP to the fullerene, suggesting the suitability of these complexes for use in organic photovoltaic devices.

Assessment of electronic transitions involving intermolecular charge transfer in complexes formed by fullerenes and donor-acceptor nanohoops.

Complexes formed by fullerenes C60/C70 and substituted cycloparaphenylenes with the capability of acting as donor/acceptor pairs ([10]CPAq and [10]CPTcaq nanohoops) have been studied using density functional theory methods empirically corrected for dispersion. All nanohoops form stable complexes with fullerenes, with complexation energies amounting to around -32 kcal mol-1 with C60 and reaching between -36 and -39 kcal mol-1 in the case of C70. According to DFT calculations, the rings are too large to appropriately accommodate the fullerene, which moves from the centre of the ring to a side region (in most cases located on the side opposite the anthracene unit). In this way, the rings are deformed (the oval is stretched) in order to better accommodate the fullerene. Anyway, the orientation and position of the fullerenes inside the nanohoop have moderate influence on the stability. The preference for a given structure is the result of the combined effect of larger dispersion energies and smaller energy costs associated with the deformation of the ring. The analysis of the electronic transitions of the different complexes suggests that the presence of the anthracene unit promotes the appearance of intermolecular (nanohoop to fullerene) charge transfer transitions, even though no direct participation of the substituent has been observed.

Early recruitment of coronary collateral circulation: impact in late presentation nonreperfused acute coronary occlusion.

BACKGROUND: Debate still remains on whether the presence of early recruited collateral circulation (ERCC) in the setting of an acute coronary occlusion (ACO) has a prognosis benefit. Some previous reports have shown lower mortality and morbidity rates in well-collateralized patients compared with those with poorly recruited collateral circulation (PCC), but others have not. In the primary angioplasty era, the role of collateral circulation in these studies may have been influenced by the effect of early reperfusion. The actual impact of ERCC in ACO can be clarified by studying its effect on nonreperfused patients. OBJECTIVE: This study aimed to compare the 1-year clinical outcome in nonreperfused late presentation ACO in a major coronary artery with ERCC versus PCC. PATIENTS AND METHODS: Between 2008 and 2015, we included 164 patients with a nonreperfused late presentation ACO. The patients were divided according to the presence of angiographic ERCC (Rentrop 2-3) or PCC (Rentrop 0-1). ERCC was present in 54% of patients. Patients with ERCC less often presented with cardiogenic shock (P=0.02) and the right coronary artery was the most frequent culprit vessel (P=0.02). The presence of PCC was associated independently with higher 1-year cardiovascular mortality [hazard ratio (HR): 6.92; 95% confidence interval (95%CI): 1.37-34.7; P=0.019], 1-year total mortality (HR: 5.79; 95%CI: 1.95-17.1; P=0.001), and 1-year major adverse cardiac event (HR: 8.05; 95%CI: 1.73-37.4; P<0.01). CONCLUSION: The presence of angiographically PCC in the setting of late presentation nonreperfused ACO is relatively infrequent (46%) and is associated with worse 1-year major clinical outcomes.

Influence of Multiple Conformations and Paths on Rate Constants and Product Branching Ratios. Thermal Decomposition of 1-Propanol Radicals.

The potential energy surface involved in the thermal decomposition of 1-propanol radicals was investigated in detail using automated codes (tsscds2018 and Q2DTor). From the predicted elementary reactions, a relevant reaction network was constructed to study the decomposition at temperatures in the range 1000-2000 K. Specifically, this relevant network comprises 18 conformational reaction channels (CRCs), which in general exhibit a large wealth of conformers of reactants and transition states. Rate constants for all the CRCs were calculated using two approaches within the formulation of variational transition-state theory (VTST), as incorporated in the TheRa program. The simplest, one-well (1W) approach considers only the most stable conformer of the reactant and that of the transition state. In the second, more accurate approach, contributions from all the reactant and transition-state conformers are taken into account using the multipath (MP) formulation of VTST. In addition, kinetic Monte Carlo (KMC) simulations were performed to compute product branching ratios. The results show significant differences between the values of the rate constants calculated with the two VTST approaches. In addition, the KMC simulations carried out with the two sets of rate constants indicate that, depending on the radical considered as reactant, the 1W and the MP approaches may display different qualitative pictures of the whole decomposition process.

Percutaneous coronary intervention for treating de-novo lesions in small coronary vessels: initial experience with the Essential paclitaxel-coated balloon.

BACKGROUND: Paclitaxel-coated balloon (PCB) coronary angioplasty is an alternative treatment for de-novo coronary lesions in small vessels. This study with the new Essential PCB aimed to evaluate early and mid-term clinical outcomes following angioplasty with the Essential PCB in the treatment of de-novo lesions in small vessels. PATIENTS AND METHODS: We included all patients who underwent PCB angioplasty for treating de-novo coronary lesions in small vessels (reference diameter <2.5 mm) between October 2015 and June 2016 in 2 centres. The primary endpoint was the 12-month target lesion failure (TLF) rate: a composite of cardiac death, target vessel-related myocardial infarction, and target lesion revascularization. The secondary endpoints were rates of target vessel failure and global major adverse cardiac events (MACE). RESULTS: A total of 71 patients (comprising 71 lesions) were included, with a mean age of 66±11 years. A 56% were diabetic and 70% had an acute coronary syndrome as an indication for coronary revascularization. The mean vessel diameter and lesion length were 2.21±0.41 and 20.7±9.2 mm, respectively. Predilatation was performed in 85.9% of patients. The median diameter, length, and inflation pressure of the Essential balloon were 2.0 [interquartile range (IQR): 2.0-2.5] mm, 20 (IQR: 15-30) mm, and 12±2 atmospheres, respectively. Angiographic success was achieved in 97.2% of cases, and bail-out stenting was required in nine (12.7%) cases. The incidence of TLF at the 12-month follow-up was 4.2%, with a target lesion revascularization rate of 4.2%. Target vessel failure and global MACE rates were 4.2 and 9.9%, respectively. CONCLUSION: Use of the Essential PCB for treating de-novo coronary lesions in small vessels was safe, with low TLF and MACE rates at the 12-month follow-up.

On the Nature of σ-σ, σ-π, and π-π Stacking in Extended Systems.

Stacking interactions have been evaluated, employing computational methods, in dimers formed by analogous aliphatic and aromatic species of increasing size. Changes in stability as the systems become larger are mostly controlled by the balance of increasing repulsion and dispersion contributions, while electrostatics plays a secondary but relevant role. The interaction energy increases as the size of the system grows, but it does much faster in π-π dimers than in σ-π complexes and more remarkably than in σ-σ dimers. The main factor behind the larger stability of aromatic dimers compared to complexes containing aliphatic molecules is related to changes in the properties of the aromatic systems due to electron delocalization leading to larger dispersion contributions. Besides, an extra stabilization in π-π complexes is due to the softening of the repulsive wall in aromatic species that allows the molecules to come closer.

Dissecting the concave-convex π-π interaction in corannulene and sumanene dimers: SAPT(DFT) analysis and performance of DFT dispersion-corrected methods.

The characteristics of the concave-convex π-π interactions are evaluated in 32 buckybowl dimers formed by corannulene, sumanene, and two substituted sumanenes (with S and CO groups), using symmetry-adapted perturbation theory [SAPT(DFT)] and density functional theory (DFT). According to our results, the main stabilizing contribution is dispersion, followed by electrostatics. Regarding the ability of DFT methods to reproduce the results obtained with the most expensive and rigorous methods, TPSS-D seems to be the best option overall, although its results slightly tend to underestimate the interaction energies and to overestimate the equilibrium distances. The other two tested DFT-D methods, B97-D2 and B3LYP-D, supply rather reasonable results as well. M06-2X, although it is a good option from a geometrical point of view, leads to too weak interactions, with differences with respect to the reference values amounting to about 4 kcal/mol (25% of the total interaction energy). © 2017 Wiley Periodicals, Inc.

Acceleration Time and Ratio of Acceleration Time to Ejection Time in Aortic Stenosis: New Echocardiographic Diagnostic Parameters.

BACKGROUND: Inconsistencies between gradients and aortic valve area are frequent in the echocardiographic evaluation of aortic stenosis (AS). Assessing AS severity is essential for the correct management of the disease. The aim of this study was to evaluate whether ejection dynamics, particularly acceleration time (AT) and the ratio of AT to ejection time (ET), could be diagnostic parameters in patients with AS. METHODS: Patients with AS (aortic peak velocity > 2 m/sec) were prospectively enrolled. Quantitative echocardiographic Doppler parameters including ejection dynamics (AT, ET, and AT/ET ratio) as well as conventional and clinical parameters were analyzed. AT, ET, and AT/ET ratio were calculated in different stages of AS. A receiver operating characteristic curve was plotted to determine the best cutoff value to identify severe AS. RESULTS: Two hundred sixty-two patients were included (mean age, 75 ± 8 years; 54% women), of whom 109 (42%) had severe AS, 99 (38%) had moderate AS, 22 (8%) had mild AS, 24 (9%) had classical low-flow, low-gradient severe AS, and eight (3%) had paradoxical low-flow, low-gradient severe AS. AT was higher in patients with higher levels of severity of AS (65 ± 16 vs 82 ± 19 vs 109 ± 23 msec, P < .001) as well as AT/ET ratios (0.22 ± 0.05 vs 0.29 ± 0.07 vs 0.37 ± 0.06, P < .001). Using a cutoff of 94 msec, AT had sensitivity of 71% and specificity of 81% for severe AS; using a cutoff of 0.35, the AT/ET ratio had sensitivity of 59% and specificity of 86%. On multivariate analysis, AT was associated with effective orifice area (B = -0.64, P < .001) and ET with heart rate (B = -0.62, P < .001) and age (B = 0.30, P = .04). CONCLUSIONS: Ejection dynamics parameters, such as AT and AT/ET, can help evaluate AS severity.

Platelet-Derived Mitochondria Display Embryonic Stem Cell Markers and Improve Pancreatic Islet ß-cell Function in Humans.

Diabetes is a major global health issue and the number of individuals with type 1 diabetes (T1D) and type 2 diabetes (T2D) increases annually across multiple populations. Research to develop a cure must overcome multiple immune dysfunctions and the shortage of pancreatic islet ß cells, but these challenges have proven intractable despite intensive research effort more than the past decades. Stem Cell Educator (SCE) therapy-which uses only autologous blood immune cells that are externally exposed to cord blood stem cells adhering to the SCE device, has previously been proven safe and effective in Chinese and Spanish subjects for the improvement of T1D, T2D, and other autoimmune diseases. Here, 4-year follow-up studies demonstrated the long-term safety and clinical efficacy of SCE therapy for the treatment of T1D and T2D. Mechanistic studies found that the nature of platelets was modulated in diabetic subjects after receiving SCE therapy. Platelets and their released mitochondria display immune tolerance-associated markers that can modulate the proliferation and function of immune cells. Notably, platelets also expressed embryonic stem cell- and pancreatic islet ß-cell-associated markers that are encoded by mitochondrial DNA. Using freshly-isolated human pancreatic islets, ex vivo studies established that platelet-releasing mitochondria can migrate to pancreatic islets and be taken up by islet ß cells, leading to the proliferation and enhancement of islet ß-cell functions. These findings reveal new mechanisms underlying SCE therapy and open up new avenues to improve the treatment of diabetes in clinics. Stem Cells Translational Medicine 2017;6:1684-1697.

Fibroblasts accelerate islet revascularization and improve long-term graft survival in a mouse model of subcutaneous islet transplantation.

Pancreatic islet transplantation has been considered for many years a promising therapy for beta-cell replacement in patients with type-1 diabetes despite that long-term clinical results are not as satisfactory. This fact points to the necessity of designing strategies to improve and accelerate islets engraftment, paying special attention to events assuring their revascularization. Fibroblasts constitute a cell population that collaborates on tissue homeostasis, keeping the equilibrium between production and degradation of structural components as well as maintaining the required amount of survival factors. Our group has developed a model for subcutaneous islet transplantation using a plasma-based scaffold containing fibroblasts as accessory cells that allowed achieving glycemic control in diabetic mice. Transplanted tissue engraftment is critical during the first days after transplantation, thus we have gone in depth into the graft-supporting role of fibroblasts during the first ten days after islet transplantation. All mice transplanted with islets embedded in the plasma-based scaffold reversed hyperglycemia, although long-term glycemic control was maintained only in the group transplanted with the fibroblasts-containing scaffold. By gene expression analysis and histology examination during the first days we could conclude that these differences might be explained by overexpression of genes involved in vessel development as well as in ß-cell regeneration that were detected when fibroblasts were present in the graft. Furthermore, fibroblasts presence correlated with a faster graft re-vascularization, a higher insulin-positive area and a lower cell death. Therefore, this work underlines the importance of fibroblasts as accessory cells in islet transplantation, and suggests its possible use in other graft-supporting strategies.

A theoretical study of complexes formed between cations and curved aromatic systems: electrostatics does not always control cation-π interaction.

The present work studies the interaction of two extended curved π-systems (corannulene and sumanene) with various cations (sodium, potassium, ammonium, tetramethylammonium, guanidinium and imidazolium). Polyatomic cations are models of groups found in important biomolecules in which cation-π interaction plays a fundamental role. The results indicate an important size effect: with extended π systems and cations of the size of potassium and larger, dispersion is much more important than has been generally recognized for cation-π interactions. In most of the systems studied here, the stability of the cation-π complexes is the result of a balanced combination of electrostatic, induction and dispersion contributions. None of the systems studied here owes its stability to the electrostatic interaction more than 42%. Induction dominates stabilization in complexes with sodium, and in some of the potassium and ammonium complexes. In complexes with large cations and with flat cations dispersion is the major stabilizing contribution and can provide more than 50% of the stabilization energy. This implies that theoretical studies of the cation-π interaction involving large or even medium-size fragments require a level of calculation capable of properly modelling dispersion. The separation between the cation and the π system is another important factor to take into account, especially when the fragments of the cation-π complex are bound (for example, to a protein backbone) and cannot interact at the most favourable distance.