Discovering trends in the Lewis acidity of beryllium and magnesium hydrides and fluorides with increasing clusters size.

We have reported in the last years the strong effect that Be- and Mg-containing Lewis acids have on the intrinsic properties of typical bases, which become acids upon complexation. In an effort to investigate these changes when the Be and Mg derivatives form clusters of increasing size, we have examined the behavior of the (MX2)n (M = Be, Mg; X = H, F; n = 1, 2, 3) clusters when they interact with ammonia, methanimine, hydrogen cyanide and pyridine, and with their corresponding deprotonated forms. The complexes obtained at the M06-2X/aug-cc-pVTZ level were analyzed using the MBIE energy decomposition formalism, in parallel with QTAIM, ELF, NCIPLOT and AdNDP analyses of their electron density. For n = 1 the interaction enthalpy for the different families of monomers, Be (Mg) hydrides and Be (Mg) fluorides, follows the same trend as the intrinsic basicity of the base that interacts with them. This interaction is greatly reinforced after the deprotonation of the base, resulting in a significant enhancement of the intrinsic acidity of the corresponding MX2-Base complex. For (MX2)2 clusters a further reinforcement of the interaction with the base is observed, this reinforcement being again larger for the deprotonated complexes. However, the concomitant increase of their intrinsic acidity is one order of magnitude larger for hydrides than for fluorides. Unexpectedly, the cyclic conformers (MX2)3, which are more unstable than the linear ones, become the global minima after association with the base and the same is true for the deprotonated complex. Accordingly, a further increase of the intrinsic acidity of the (MX2)3-Base complexes with respect to the (MX2)2-Base ones is observed. This effect is maximum for (MgF2)3 clusters, to the point that the (MgF2)3-Base complexes become more acidic than nitric acid, the extreme case being the cluster (MgF2)3-NCH, whose acidity is higher than that of perchloric acid.

Ionization, intrinsic basicity, and intrinsic acidity of unsaturated diols of astrochemical interest: 1,1- and 1,2-ethenediol: A theoretical survey.

The structure, stability, and bonding characteristics of 1,1- and 1,2-ethenediol, their radical cations, and their protonated and deprotonated species were investigated using high-level ab initio G4 calculations. The electron density of all the neutral and charged systems investigated was analyzed using the QTAIM, ELF, and NBO approaches. The vertical ionization potential (IP) of the five stable tautomers of 1,2-ethenediol and the two stable tautomers of 1,1-ethenediol go from 11.81 to 12.27 eV, whereas the adiabatic ones go from 11.00 to 11.72 eV. The adiabatic ionization leads to a significant charge delocalization along the O-C-C-O skeleton. The most stable protonated form of (Z)-1,2-ethenediol can be reached by the protonation of both the anti-anti and the syn-anti conformers, whereas the most stable deprotonated form arises only from the syn-anti one. Both charged species are extra-stabilized by the formation of an O-H···O intramolecular hydrogen bond (IHB) which is not found in the neutral system. (Z)-1,2-ethenediol is predicted to be less stable, less basic, and more acidic than its cis-glycolaldehyde isomer. The most stable protonated species of (E)-1,2-ethenediol comes from its syn-syn conformer, although the anti-anti conformer is the most basic one. Contrarily, the three conformers yield a common deprotonated species, so their acidity follows exactly their relative stability. Again, the (E)-1,2-ethenediol is predicted to be less stable, less basic, and more acidic than its trans-glycolaldehyde isomer. Neither the neutral nor the protonated or the deprotonated forms of 1,1-ethenediol show the formation of any O-H···O IHB. The most stable protonated species is formed by the protonation of any of the two tautomers, but the most stable deprotonated form arises exclusively from the syn-anti neutral conformer. The conformers of 1,1-ethenediol are much less stable and significantly less basic than their isomer, acetic acid, and only slightly more acidic.

Systemic biomarker associated with poor outcome after futile reperfusion.

BACKGROUND: Successful recanalization does not lead to complete tissue reperfusion in a considerable percentage of ischemic stroke patients. This study aimed to identify biomarkers associated with futile recanalization. Leukoaraiosis predicts poor outcomes of this phenomenon. Soluble tumour necrosis factor-like weak inducer of apoptosis (sTWEAK), which is associated with leukoaraiosis degrees, could be a potential biomarker. METHODS: This study includes two cohorts of ischemic stroke patients in a multicentre retrospective observational study. Effective reperfusion, defined as a reduction of ≥8 points in the National Institutes of Health Stroke Scale (NIHSS) within the first 24 h, was used as a clinical marker of effective reperfusion. RESULTS: In the first cohort study, female sex, age, and high NIHSS at admission (44.7% vs. 81.1%, 71.3 ± 13.7 vs. 81.1 ± 6.7; 16 [13, 21] vs. 23 [17, 28] respectively; p < .0001) were confirmed as predictors of futile recanalization. ROC curve analysis showed that leukocyte levels (sensitivity of 99%, specificity of 55%) and sTWEAK level (sensitivity of 92%, specificity of 88%) can discriminate between poor and good outcomes. Both biomarkers simultaneously are higher associated with outcome after effective reperfusion (OR: 2.17; CI 95% 1.63-4.19; p < .0001) than individually (leukocytes OR: 1.38; CI 95% 1.00-1.64, p = .042; sTWEAK OR: 1.00; C I95% 1.00-1.01, p = .019). These results were validated using a second cohort, where leukocytes and sTWEAK showed a sensitivity of 100% and specificity of 66.7% and 75% respectively. CONCLUSIONS: Leukocyte and sTWEAK could be biomarkers of reperfusion failure and subsequent poor outcomes. Further studies will be necessary to explore its role in reperfusion processes.

Precision Medicine for Blood Glutamate Grabbing in Ischemic Stroke.

Glutamate grabbers, such as glutamate oxaloacetate transaminase (GOT), have been proposed to prevent excitotoxicity secondary to high glutamate levels in stroke patients. However, the efficacy of blood glutamate grabbing by GOT could be dependent on the extent and severity of the disruption of the blood-brain barrier (BBB). Our purpose was to analyze the relationship between GOT and glutamate concentration with the patient's functional status differentially according to BBB serum markers (soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) and leukoaraiosis based on neuroimaging). This retrospective observational study includes 906 ischemic stroke patients. We studied the presence of leukoaraiosis and the serum levels of glutamate, GOT, and sTWEAK in blood samples. Functional outcome was assessed using the modified Rankin Scale (mRS) at 3 months. A significant negative correlation between GOT and glutamate levels at admission was shown in those patients with sTWEAK levels > 2900 pg/mL (Pearson's correlation coefficient: -0.249; p < 0.0001). This correlation was also observed in patients with and without leukoaraiosis (Pearson's correlation coefficients: -0.299; p < 0.001 vs. -0.116; p = 0.024). The logistic regression model confirmed the association of higher levels of GOT with lower odds of poor outcome at 3 months when sTWEAK levels were >2900 pg/mL (OR: 0.41; CI 95%: 0.28-0.68; p < 0.0001) or with leukoaraiosis (OR: 0.75; CI 95%: 0.69-0.82; p < 0.0001). GOT levels are associated with glutamate levels and functional outcomes at 3 months, but only in those patients with leukoaraiosis and elevated sTWEAK levels. Consequently, therapies targeting glutamate grabbing might be more effective in patients with BBB dysfunction.

Dismantlement of ammonia upon interaction with Ben (n ≤ 10) clusters.

The interaction of ammonia with Ben (n < 1-10) clusters has been investigated by density functional theory and ab initio calculations. The main conclusion is that, regardless of the size of the Be cluster, neither the structure of ammonia nor that of the Be clusters are preserved due to a systematic dissociation of its NH bonds and a spontaneous H-shift toward the available Be atoms. This H migration not only leads to rather stable BeH bonds, but dramatically enhances the strength of the BeN bonds as well. Accordingly, the maximum stability is found for the interaction with the beryllium trimer, leading to a complex with three NBe and three BeH bonds. Another maximum in stability, although lower than that reached for n = 3, is found for the Be heptamer, since from n = 6, a new NBe bond is formed, so that complexes from n = 6 to n = 10 are characterized by the formation of a NBe4 moiety, whose stability reaches a maximum at n = 7. The bonding characteristics of the different species formed are analyzed by means of AIM, NBO, ELF and AdNDP approaches.

Dispersion, Rehybridization, and Pentacoordination: Keys to Understand Clustering of Boron and Aluminum Hydrides and Halides.

The structure, stability, and bonding characteristics of dimers and trimers involving BX3 and AlX3 (X = H, F, Cl) in the gas phase, many of them explored for the first time, were investigated using different DFT (B3LYP, B3LYP/D3BJ, and M06-2X) and ab initio (MP2 and G4) methods together with different energy decomposition formalisms, namely, many-body interaction-energy and localized molecular orbital energy decomposition analysis. The electron density of the clusters investigated was analyzed with QTAIM, electron localization function, NCIPLOT, and adaptive natural density partitioning approaches. Our results for triel hydride dimers and Al2X6 (X = F, Cl) clusters are in good agreement with previous studies in the literature, but in contrast with the general accepted idea that B2F6 and B2Cl6 do not exist, we have found that they are predicted to be weakly bound systems if dispersion interactions are conveniently accounted for in the theoretical schemes used. Dispersion interactions are also dominant in both homo- and heterotrimers involving boron halide monomers. Surprisingly, B3F9 and B3Cl9 C3v cyclic trimers, in spite of exhibiting rather strong B-X (X = F, Cl) interactions, were found to be unstable with respect to the isolated monomers due to the high energetic cost of the rehybridization of the B atom, which is larger than the two- and three-body stabilization contributions when the cyclic is formed. Another important feature is the enhanced stability of both homo- and heterotrimers in which Al is the central atom because Al is systematically pentacoordinated, whereas this is not the case when the central atom is B, which is only tri- or tetra-coordinated.

Association of periodontitis with cognitive decline and its progression: Contribution of blood-based biomarkers of Alzheimer's disease to this relationship.

AIM: To assess whether periodontitis is associated with cognitive decline and its progression as well as with certain blood-based markers of Alzheimer's disease. MATERIALS AND METHODS: Data from a 2-year follow-up prospective cohort study (n = 101) was analysed. Participants with a previous history of hypertension and aged ≥60 years were included in the analysis. All of them received a full-mouth periodontal examination and cognitive function assessments (Addenbrooke's Cognitive Examination (ACE) and Mini-Mental State Examination [MMSE]). Plasma levels of amyloid beta (Aß)1-40 , Aß1-42 , phosphorylated and total Tau (p-Tau and t-Tau) were determined at baseline, 12 and 24 months. RESULTS: Periodontitis was associated with poor cognitive performance (MMSE: ß = -1.5 [0.6]) and progression of cognitive impairment (hazard ratio [HR] = 1.8; 95% confidence interval: 1.0-3.1). Subjects with periodontitis showed greater baseline levels of p-Tau (1.6 [0.7] vs. 1.2 [0.2] pg/mL, p < .001) and Aß1-40 (242.1 [77.3] vs. 208.2 [73.8] pg/mL, p = .036) compared with those without periodontitis. Concentrations of the latter protein also increased over time only in the periodontitis group (p = .005). CONCLUSIONS: Periodontitis is associated with cognitive decline and its progression in elderly patients with a previous history of hypertension. Overexpression of p-Tau and Aß1-40 may play a role in this association.

Periodontitis is associated with subclinical cerebral and carotid atherosclerosis in hypertensive patients: A cross-sectional study.

OBJECTIVE: To examine the relationship between periodontitis and subclinical intracranial atherosclerosis. The association of periodontitis with preclinical markers of atherosclerosis in other vascular territories was also explored. MATERIAL AND METHODS: This was a cross-sectional study where 97 elderly subjects with a previous history of hypertension received an ultrasonographic evaluation to assess subclinical atherosclerosis in different vascular territories: (1) cerebral [pulsatility (PI) and resistance index (RI) of the middle cerebral artery], (2) carotid [intima-media thickness (IMT)], and (3) peripheral [ankle-brachial index (ABI)]. Additionally, participants underwent a full-mouth periodontal assessment together with blood sample collection to determine levels of inflammatory biomarkers (leukocytes, fibrinogen, and erythrocyte sedimentation rate), lipid fractions (total cholesterol and high- and low-density lipoprotein), and glucose. RESULTS: Sixty-one individuals had periodontitis. Compared to subjects without periodontitis, those with periodontitis showed higher values of PI (1.24 ± 0.29 vs 1.01 ± 0.16), RI (0.70 ± 0.14 vs 0.60 ± 0.06), and IMT (0.94 ± 0.15 vs 0.79 ± 0.15) (all p < 0.001). No statistically significant differences were found neither for ABI or for other clinical and biochemical parameters. An independent association was found between periodontitis and increased intracranial atherosclerosis (ORadjusted = 10.16; 95% CI: 3.14-32.90, p < 0.001) and to a lesser extent with thicker carotid IMT (ORadjusted = 4.10; 95% CI: 1.61-10.48, p = 0.003). CONCLUSIONS: Periodontitis is associated with subclinical atherosclerosis in both intracranial and carotid arteries in elderly subjects with hypertension. CLINICAL RELEVANCE: The association of periodontitis with intracranial atherosclerosis implies that periodontitis patients might have greater chances to develop ischemic stroke in the future.

Influence of Temperature Chronobiology on Stroke Outcome.

The circadian system regulates numerous physiological variables, including body temperature. Additionally, a circadian patter has been described in stroke onset. Considering this, we hypothesised that the chronobiology of temperature may have an impact on stroke onset and functional outcomes. We also studied the variation of blood biomarkers according to stroke onset time. This is a retrospective observational study. Of the patients included, 2763 had a stroke between midnight and 8:00 h; 1571 between 8:00-14:00 h; and 655 between 14:00 h and midnight. Axillary temperature was measured at admission. At this time, blood samples were collected for biomarker analysis (TNF-α, IL-1ß, IL-6, IL-10, and glutamate). Temperature was higher in patients admitted from 8:00 h to midnight (p < 0.0001). However, the percentage of poor outcome at 3 months was highest in patients from midnight to 8:00 h (57.7%, p < 0.001). The association between temperature and mortality was highest during night time (OR: 2.79; CI 95%: 2.36-3.28; p < 0.001). These patients exhibited high glutamate (220.2 ± 140.2 µM), IL-6 (32.8 ± 14.3 pg/mL) and low IL-10 (9.7 ± 14.3 pg/mL) levels. Therefore, temperature chronobiology could have a significant impact on stroke onset and functional outcome. Superficial body hyperthermia during sleep seems to be more dangerous than during wakefulness. Further studies will be necessary to confirm our data.

A Holistic View of the Interactions between Electron-Deficient Systems: Clustering of Beryllium and Magnesium Hydrides and Halides.

In the search for common bonding patterns in pure and mixed clusters of beryllium and magnesium derivatives, the most stable dimers and trimers involving BeX2 and MgX2 (X = H, F, Cl) have been studied in the gas phase using B3LYP and M06-2X DFT methods and the G4 ab initio composite procedure. To obtain some insight into their structure, stability, and bonding characteristics, we have used two different energy decomposition formalisms, namely MBIE and LMO-EDA, in parallel with the analysis of the electron density with the help of QTAIM, ELF, NCIPLOT, and AdNDP approaches. Some interesting differences are already observed in the dimers, where the stability sequence observed for the hydrides differs entirely from that of the fluorides and chlorides. Trimers also show some peculiarities associated with the presence of compact trigonal cyclic structures that compete in stability with the more conventional hexagonal and linear forms. As observed for dimers, the stability of the trimers changes significantly from hydrides to fluorides or chlorides. Although some of these clusters were previously explored in the literature, the novelty of this work is to provide a holistic approach to the entire series of compounds by using chemical bonding tools, allowing us to understand the stability trends in detail and providing insights for a significant number of new, unexplored structures.

Surrogate biomarkers of outcome for wake-up ischemic stroke.

BACKGROUND: Wake-up ischemic stroke (IS) has been usually excluded from acute stroke therapy options for being outside of the safe treatment window. We identified risk factors, and clinical or molecular biomarkers that could be therapeutic targets for wake-up stroke prevention, thus hopefully leading to a decrease in its mortality and disability in medium to long-term outcome. METHODS: 4251 ischemic stroke (IS) patients from a prospectively registered database were recruited; 3838 (90.3%) had known onset-symptom time, and 413 (9.7%) were wake-up strokes. The main endpoint was to analyze the association between different serum biomarkers with wake-up IS episodes and their progression. Leukocytes count, serum levels of C-reactive protein, fibrinogen, interleukin 6 (IL-6), and vitamin D were analyzed as inflammation biomarkers; N-terminal pro-B-type Natriuretic-Peptide and microalbuminuria, used as atrial/endothelial dysfunction biomarkers; finally, glutamate levels as excitotoxicity biomarker. In addition, demographic, clinical and neuroimaging variables associated with the time-evolution of wake-up IS patients and functional outcome at 3 months were evaluated. Good and poor functional outcome were defined as mRS ≤2 and mRS > 2 at 3 months, respectively. RESULTS: Wake-up IS showed a poorer outcome at 3-months than in patients with known on-set-symptom time (59.1% vs. 48.1%; p < 0.0001). Patients with wake-up IS had higher levels of inflammation biomarkers; IL-6 levels at admission (51.5 ± 15.1 vs. 27.8 ± 18.6 pg/ml; p < 0.0001), and low vitamin D levels at 24 h (5.6 ± 5.8 vs. 19.2 ± 9.4 ng/ml; p < 0.0001) are worthy of attention. In a logistic regression model adjusted for vitamin D, OR was 15.1; CI 95%: 8.6-26.3, p < 0.0001. However, we found no difference in vitamin D levels between patients with or without clinical-DWI mismatch (no: 18.95 ± 9.66; yes: 17.84 ± 11.77 ng/mL, p = 0.394). No difference in DWI volume at admission was found (49.3 ± 96.9 ml in wake-up IS patients vs. 51.7 ± 98.2 ml in awake IS patients; p = 0.895). CONCLUSIONS: Inflammatory biomarkers are the main factors that are strongly associated with wake-up IS episodes. Wake-up IS is associated with lower vitamin D levels. These data indicate that vitamin D deficiency could become a therapeutic target to reduce wake-up IS events.

Open questions on toxic heavy metals Cd, Hg and Pb binding small components of DNA and nucleobases. Are there any predictable trends?

In this perspective article, we provide a bibliographic compilation of experimental and theoretical work on Cd, Hg, and Pb, and analyze in detail the bonding of M2+ and CH3M+ (M = Zn, Cd, Hg, Pb) with urea and thiourea as suitable models for larger biochemical bases. Through the use of DFT calculations, we have found that although in principle binding energies decrease according to ionic size (Zn2+ > Cd2+ > Pb2+), Hg2+ largely breaks the trend. Through the use of EDA (Energy Decomposition Analysis) it is possible to explain this behavior, which is essentially due to the strong contribution of polarization to the binding. This conclusion is ratified by the NEDA (Natural Energy Decomposition Analysis) formalism, showing that the charge transfer term is very large in all cases, but particularly in the case of the mercury-thiourea system. The general trends observed for the interactions with CH3M+ monocations show however CH3Hg+ binding energies systematically smaller than the CH3Zn+ ones, likely because the relativistic contraction of the Hg orbitals is very much attenuated by the attachment to the methyl group. Finally, we have investigated the gas-phase reactivity between EtHg+ and uracil to compare it with that exhibited by CH3Hg+ and n-ButHg+ previously described in the literature. This comparison gathers new information that highlights the importance of the length of the alkyl chain attached to the metal on the mechanisms of these reactions. For methyl mercury, only the alkyl transfer process is allowed; for butyl mercury, protonation is clearly favored, and for ethyl mercury, both paths are competitive experimentally.

Disrupting bonding in azoles through beryllium bonds: Unexpected coordination patterns and acidity enhancement.

Although triazoles and tetrazole are amphoteric and may behave as weak acids, the latter property can be hugely enhanced by beryllium bonds. To explain this phenomenon, the structure and bonding characteristics of the complexes between triazoles and tetrazoles with one and two molecules of BeF2 have been investigated through the use of high-level G4 ab initio calculations. The formation of the complexes between the N basic sites of the azoles and the Be center of the BeF2 molecule and the (BeF2)2 dimer leads to a significant bonding perturbation of both interacting subunits. The main consequence of these electron density rearrangements is the above-mentioned increase in the intrinsic acidity of the azole subunit, evolving from a typical nitrogen base to a very strong nitrogenous acid. This effect is particularly dramatic when the interaction involves the (BeF2)2 dimer, that is, a Lewis acid much stronger than the monomer. Although the azoles investigated have neighboring N-basic sites, their interaction with the (BeF2)2 dimer yields a monodentate complex. However, the deprotonated species becomes extra-stabilized because a second N-Be bond is formed, leading to a new five-membered ring, with the result that the azole-(BeF2)2 complexes investigated become stronger nitrogenous acids than oxyacids such as perchloric acid.

Spontaneous bond dissociation cascades induced by Ben clusters (n = 2,4).

High-level single and multireference ab initio calculations show that the Be4 cluster behaves as a very efficient Lewis acid when interacting with conventional Lewis bases such as ammonia, water or hydrogen fluoride, to the point that the corresponding acid-base interaction triggers a sequential dissociation of all the bonds of the Lewis base. Notably, this behavior is already found for the simplest beryllium cluster, the Be2 dimer. However, whereas for Be2 the first dissociation process involves a low activation barrier which is above the reactants, for Be4 all the bond dissociation processes involve barriers below the entrance channel leading to a cascade of successive exothermic processes, which end up spontaneously in a global minimum in which the bonding patterns of both the base and the Lewis acid are completely destroyed. Indeed, the global minimum, in all cases, is stabilized by three-center Be-H-Be bonds and covalent interactions between the Be atoms and the basic center of the base, which replace the initial metallic bond stabilizing the Be4 cluster. As a consequence, in the global minimum the basic atoms (N, O and F) behave as hyper-coordinated centers. Also importantly, the Be4 cluster and its complexes present RHF-UHF instabilities (not reported before for Be4), which require the use of multireference methods to correctly describe them.

Perturbating Intramolecular Hydrogen Bonds through Substituent Effects or Non-Covalent Interactions.

An analysis of the effects induced by F, Cl, and Br-substituents at the α-position of both, the hydroxyl or the amino group for a series of amino-alcohols, HOCH2(CH2)nCH2NH2 (n = 0-5) on the strength and characteristics of their OH···N or NH···O intramolecular hydrogen bonds (IMHBs) was carried out through the use of high-level G4 ab initio calculations. For the parent unsubstituted amino-alcohols, it is found that the strength of the OH···N IMHB goes through a maximum for n = 2, as revealed by the use of appropriate isodesmic reactions, natural bond orbital (NBO) analysis and atoms in molecules (AIM), and non-covalent interaction (NCI) procedures. The corresponding infrared (IR) spectra also reflect the same trends. When the α-position to the hydroxyl group is substituted by halogen atoms, the OH···N IMHB significantly reinforces following the trend H < F < Cl < Br. Conversely, when the substitution takes place at the α-position with respect to the amino group, the result is a weakening of the OH···N IMHB. A totally different scenario is found when the amino-alcohols HOCH2(CH2)nCH2NH2 (n = 0-3) interact with BeF2. Although the presence of the beryllium derivative dramatically increases the strength of the IMHBs, the possibility for the beryllium atom to interact simultaneously with the O and the N atoms of the amino-alcohol leads to the global minimum of the potential energy surface, with the result that the IMHBs are replaced by two beryllium bonds.

Enthalpies of Adduct Formation between Boron Trifluoride and Selected Organic Bases in Solution: Toward an Accurate Theoretical Entry to Lewis Basicity.

The Lewis basicity of selected organic bases, modeled by the enthalpies of adduct formation between gaseous BF3 and bases in dichloromethane (DCM) solution, is critically examined. Although experimental enthalpies for a large number of molecules have been reported in the literature, it may be desirable to estimate missing or uncertain data for important Lewis bases. We decided to use high-level ab initio procedures, combined with a polarized continuum solvation model, in which the solvated species were the clusters formed by specific hydrogen bonding of DCM with the Lewis base and the Lewis base/BF3 adduct. This mode of interaction with DCM corresponds to a specific solvation model (SSM). The results essentially showed that the enthalpy of BF3 adduct formation in DCM solution was clearly influenced by specific interactions, with DCM acting as hydrogen-bonding donor (HBD) molecule in two ways: base/DCM and adduct/DCM, confirming that specific solvation is an important contribution to experimentally determined Lewis basicity scales. This analysis allowed us to conclude that there are reasons to suspect some gas-phase values to be in error by more than the stated experimental uncertainty. Some experimental values in DCM solution that were uncertain for identified reasons could be complemented by the computed values.

Large Stabilization Effects by Intramolecular Beryllium Bonds in Ortho-Benzene Derivatives.

Intramolecular interactions are shown to be key for favoring a given structure in systems with a variety of conformers. In ortho-substituted benzene derivatives including a beryllium moiety, beryllium bonds provide very large stabilizations with respect to non-bound conformers and enthalpy differences above one hundred kJ·mol-1 are found in the most favorable cases, especially if the newly formed rings are five or six-membered heterocycles. These values are in general significantly larger than hydrogen bonds in 1,2-dihidroxybenzene. Conformers stabilized by a beryllium bond exhibit the typical features of this non-covalent interaction, such as the presence of a bond critical point according to the topology of the electron density, positive Laplacian values, significant geometrical distortions and strong interaction energies between the donor and acceptor quantified by using the Natural Bond Orbital approach. An isodesmic reaction scheme is used as a tool to measure the strength of the beryllium bond in these systems in terms of isodesmic energies (analogous to binding energies), interaction energies and deformation energies. This approach shows that a huge amount of energy is spent on deforming the donor-acceptor pairs to form the new rings.

From Very Strong to Inexistent Be-Be Bonds in the Interactions of Be2 with π-Systems.

Isolated Be2 is a typical example of a weakly bound system, but interaction with other systems may give rise to surprising bonding features. The interactions between Be2 and a set of selected neutral Cn Hn (n=2-8) π-systems have been analyzed through the use of G4 and G4MP2 ab initio methods, along with multireference CASPT2//CASPT2 calculations. Our results systematically show that the Cn Hn -Be2 -Cn Hn clusters formed are always very stable. However, the nature of this interaction is completely different when the π-system involved is a closed shell species (n=2, 4, 6, 8), or a radical (n=3, 5, 7). In the first case, the interaction does not occur with the π-system as a whole, but with specific C centers yielding rather polar but strong C-Be bonds. Nonetheless, although the Be-Be distances in these complexes are similar to the ones in compounds with ultra-strong Be-Be bonds, a close examination of their electron density distribution reveals that no Be-Be bonds exist. The situation is totally different when the interaction involves two π-radicals, Cn Hn -Be2 -Cn Hn (n=3, 5, 7). In these cases, a strong Be-Be bond is formed. Indeed, even though Be is electron deficient, the Be2 moiety behaves as an efficient electron donor towards the two π-radicals, so that the different Cn Hn -Be2 -Cn Hn (n=3, 5, 7) clusters are the result of the interaction between Be2 2+ and two L- anions. The characteristics of these two scenarios do not change when dealing with bicyclic π-compounds, such as naphthalene and pentalene, because the interaction with the Be2 moiety is localized on one of the unsaturated cycles, the other being almost a spectator.

Regulatory T cells participate in the recovery of ischemic stroke patients.

BACKGROUND: Recent preclinical studies have shown that regulatory T cells (Treg) play a key role in the immune response after ischemic stroke (IS). However, the role of Treg in human acute IS has been poorly investigated. Our aim was to study the relationship between circulating Treg and outcome in human IS patients. METHODS: A total of 204 IS patients and 22 control subjects were recruited. The main study variable was good functional outcome at 3 months (modified Rankin scale ≤2) considering infarct volume, Early Neurological Deterioration (END) and risk of infections as secondary variables. The percentage of circulating Treg was measured at admission, 48, 72 h and at day 7 after stroke onset. RESULTS: Circulating Treg levels were higher in IS patients compared to control subjects. Treg at 48 h were independently associated with good functional outcome (OR, 3.5; CI: 1.9-7.8) after adjusting by confounding factors. Patients with lower Treg at 48 h showed higher frequency of END and risk of infections. In addition, a negative correlation was found between circulating Treg at 48 h (r = - 0.414) and 72 h (r = - 0.418) and infarct volume. CONCLUSIONS: These findings suggest that Treg may participate in the recovery of IS patients. Therefore, Treg may be considered a potential therapeutic target in acute ischemic stroke.

Are Anions of Cyclobutane Beryllium Derivatives Stabilized through Four-Center One-Electron Bonds?

High-level G4 ab initio calculations allowed us to show that C4H4(BeX)4 (X = H, Cl) derivatives behave as rather efficient electron capturers due to their ability to trap the extra electron through the formation of a four-membered beryllium ring. This finding is in agreement with previous work showing the ability of highly electron-deficient atoms, such as beryllium, to lead to multicenter one-electron bonds. In our particular case, the formation of the four-center bond is characterized, in very good harmony, by different topological methods such as quantum theory of atoms in molecules (QTAIM), the electron localization function (ELF), and the noncovalent interactions (NCI) approach and is accompanied by large electron affinity values, around 300 kJ·mol-1, in the gas phase. Preliminary results may anticipate that the ability of groups of beryllium atoms to trap electrons decays on going to bigger systems.