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Streptococcus agalactiae es una bacteria colonizante que ha emergido en los últimos años como causante de infecciones neonatales, perinatales y en pacientes con compromiso inmunológico. La caracterización del polisacárido capsular, de las proteínas de superficie (c, X, R), así como el análisis de marcadores moleculares, permiten su clasificación en serotipos y genotipos. Esto resulta de utilidad para fines epidemiológicos y para estudios de virulencia de la bacteria. El objetivo de este trabajo fue conocer los serotipos prevalentes y la sensibilidad antimicrobiana de aislamientos provenientes de procesos infecciosos en pacientes de distintas zonas de Argentina. En la muestra analizada se obtuvo predominio de los serotipos Ia y III, seguido de II y IV. Todas las cepas resultaron sensibles a penicilina. Se observó 6% de resistencia a eritromicina y 4,5% a clindamicina. En 3 de las cepas se detectó fenotipo MLS (resistencia a macrólidos, lincosaminas y estreptograminas) constitutiva y en una cepa, resistencia MLS inducible. Los resultados logrados en este estudio destacan la importancia de efectuar un relevamiento de los serotipos más frecuentes en nuestro país en vistas a la prevención de esta infección con una vacuna que realmente sea eficaz, como así también el conocimiento de la sensibilidad antimicrobiana para lograr éxito terapéutico en los tratamientos.Streptococcus agalactiae is an endogenous bacterium that has emerged in the last 20 years as an etiological agent in both neonatal and perinatal infections, and in immunocompromised patients. The differentiation of the capsular polysaccharide, the presence of surface proteins c, X, R, and molecular methods allow classification in serotypes and genotypes. This identification is a useful tool for epidemiological purposes and virulence studies in this bacterium. The objective of this work was to study the serotypes and the antimicrobial susceptibility of isolates recovered from invasive diseases in different areas of Argentina. In the analyzed sample a fair predominance of Ia and III serotypes was recovered, followed by II and IV serotypes. All the isolates were found to be sensitive to penicillin. A 6% of resistance to erythromycin and a 4.5% to clindamycin were detected. In three of the isolates, constitutive MLS phenotype (resistance to macrolides, lincosamins and streptogramins) was founded, while in the remaining one, inducible MLS phenotype was detected. These results stress the importance of conducting a surveillance of the prevalent serotypes in our country with the goal of future prevention of this disease with an effective vaccine. The knowledge of the antimicrobial susceptibility profile will be also important to obtain therapeutic success in the treatment.

Tunneling nanotubes (TNTs) are open actin- and membrane-based channels, connecting remote cells and allowing direct transfer of cellular material (e.g. vesicles, mRNAs, protein aggregates) from the cytoplasm to the cytoplasm. Although they are important especially, in pathological conditions (e.g. cancers, neurodegenerative diseases), their precise composition and their regulation were still poorly described. Here, using a biochemical approach allowing to separate TNTs from cell bodies and from extracellular vesicles and particles (EVPs), we obtained the full composition of TNTs compared to EVPs. We then focused on two major components of our proteomic data, the CD9 and CD81 tetraspanins, and further investigated their specific roles in TNT formation and function. We show that these two tetraspanins have distinct non-redundant functions: CD9 participates in stabilizing TNTs, whereas CD81 expression is required to allow the functional transfer of vesicles in the newly formed TNTs, possibly by regulating docking to or fusion with the opposing cell., Competing Interests: RN, TC, ER, EP, MM, CZ, CB No competing interests declared, (© 2024, Notario Manzano et al.)

Background: The aim of this study was to verify the reproducibility of a resistance training protocol in the bench press (BP) exercise, based on traditional recommendations, analysing the effect of the muscle fatigue of each set and of the whole exercise protocol. Methods: In this cross-sectional study, thirty male physical education students were divided into three groups according to their relative strength ratio (RSR), and they performed a 1RM BP test (T1). In the second session (T2), which was one week after T1, the participants performed a BP exercise protocol of three sets with the maximum number of repetitions (MNR) possible to muscle failure, using a relative load corresponding to 70% 1RM determined through the mean propulsive velocity (MPV) obtained from the individual load−velocity relationship, with 2 min rests between sets. Two weeks later, a third session (T3) identical to the second session (T2) was performed. The MPV of each repetition of each set and the blood lactate level after each set were calculated, and mechanical fatigue was quantified through the velocity loss percentage of the set (% loss MPV) and in a pre-post exercise test with an individual load that could be lifted at ~1 m·s−1 of MPV. Results: The number of repetitions performed in each set was significantly different (MNR for the total group of participants: set 1 = 12.50 ± 2.19 repetitions, set 2 = 6.06 ± 1.98 repetitions and set 3 = 4.20 ± 1.99 repetitions), showing high variation coefficients in each of the sets and between groups according to RSR. There were significant differences also in MPVrep Best (set 1 = 0.62 ± 0.10 m·s−1, set 2 = 0.42 ± 0.07 m·s−1, set 3 = 0.36 ± 0.10 m·s−1), which significantly reduced the % loss MPV of all sets (set 1 = 77.4%, set 2 = 64%, set 3 = 54.2%). The lactate levels increased significantly (p < 0.05) (set 1 = 4.9 mmo·L−1, set 2 = 6 mmo·L−1, set 3 = 6.5 mmo·L−1), and MPV loss at 1 m·s−1 after performing the three sets was 36% in T2 and 34% in T3, with acceptable intrasubject variability (MPV at 1 m·s−1 pre-exercise: SEM ≤ 0.09 m·s−1, CV = 9.8%; MPV at 1 m·s−1 post-exercise: SEM ≤ 0.07 m·s−1, CV = 11.7%). Conclusions: These exercise propositions are difficult to reproduce and apply. Moreover, the number of repetitions performed in each set was significantly different, which makes it difficult to define and control the intensity of the exercise. Lastly, the fatigue generated in each set could have an individual response depending on the capacity of each subject to recover from the preceding maximum effort.

Background : The aim of the study was to analyze the use of variables such as % of one-repetition maximum (1RM) and number of maximal repetitions (xRM) with execution velocity to define and control the intensity of resistance training in bench press exercise. Hence, exercise professionals will achieve better control of training through a greater understanding of its variables. Methods: In this cross-sectional study, fifty male physical education students were divided into four groups according to their relative strength ratio (RSR) and performed a 1RM bench press test (T1). In the second test, participants performed repetitions to exhaustion (T2), using a relative load corresponding to 70% 1RM determined through the mean propulsive velocity (MPV) obtained from the individual load-velocity relationship. This same test was repeated a week later (T3). Tests were monitored according to the MPV of each repetition and blood lactate values (LACT). Results : Regarding MPV, the best (fastest) repetition of the set (MPVrep Best) values were similar between groups (0.62 m·s -1 -0.64 m·s -1 ), with significant differences in relation to the high RSR group ( p < 0.001). The average maximum number of repetitions (MNR) was 12.38 ± 2.51, with no significant differences between the RSR groups. Nonetheless, significant variation existed between groups with regards to MNR (CV: 13-29%), with greater variability in the group corresponding to the lowest RSR values (CV: 29%). The loss of velocity in the MNR test in the different groups was similar ( p > 0.05). Average LACT values (5.72 mmol·L -1 ) showed significant differences between the Medium RSR and Very Low RSR groups. No significant differences were found ( p > 0.05) between T2 and T3 with regards to MNR, MPVrep Best, or MPVrep Last, with little variability seen between participants. Conclusions : The use of variables such as the 1RM, estimated using an absolute load value, or an MNR do not allow an adequate degree of precision to prescribe and control the relative intensity of resistance training. Besides, execution velocity control can offer an adequate alternative to guarantee an accurate prescription of intensity with regard to resistance training.

The aim of this work was to determine the effect of temperature on the formation of acrylamide in cocoa beans during drying treatment by an experimental and computational study, in order to assess the presence of this neoformed compound from postharvest stage. The computational study was conducted on the reaction between fructose, glyoxal from glucose, and on asparagine at the M06-2X/6-31+G(d,p) level, under cocoa bean drying conditions at 323.15 to 343.15 K. The proposed reaction for acrylamide formation consisted of seven steps, which required to progress a via cyclic transition state of the four members. In addition, step III (decarboxylation) was considered to be the rate-determining step. Glucose followed an E1-like elimination and fructose exhibited an E1cb-like elimination. Computational model showed that the reaction of acrylamide formation was favored by fructose rather than glucose. The content of reducing sugars, asparagine and acrylamide in fermented and dried cocoa from two subregions of Antioquia-Colombia, as well as roasted cocoa, were evaluated by UHPLC-C-CAD and UHPLC-QqQ. The concentrations of monosaccharides measured at the end of the fermentation and drying process of cocoa nibs showed greater decreases in the levels of fructose as compared to glucose, supporting the main model hypothesis. Acrylamide formation only occurred in Bajo Cauca due to the presence of both precursors and fast drying time (72 h). Finally, it was possible to find the conditions to which acrylamide can be formed from the drying process and not only from roasting, information that can be used for future control strategies., (© 2020 Published by Elsevier Ltd.)

Anthropogenic mercury (Hg(0)) emissions oxidize to gaseous Hg(II) compounds, before deposition to Earth surface ecosystems. Atmospheric reduction of Hg(II) competes with deposition, thereby modifying the magnitude and pattern of Hg deposition. Global Hg models have postulated that Hg(II) reduction in the atmosphere occurs through aqueous-phase photoreduction that may take place in clouds. Here we report that experimental rainfall Hg(II) photoreduction rates are much slower than modelled rates. We compute absorption cross sections of Hg(II) compounds and show that fast gas-phase Hg(II) photolysis can dominate atmospheric mercury reduction and lead to a substantial increase in the modelled, global atmospheric Hg lifetime by a factor two. Models with Hg(II) photolysis show enhanced Hg(0) deposition to land, which may prolong recovery of aquatic ecosystems long after Hg emissions are lowered, due to the longer residence time of Hg in soils compared with the ocean. Fast Hg(II) photolysis substantially changes atmospheric Hg dynamics and requires further assessment at regional and local scales.

This study reports DFT geometry optimization of the anancomeric (ring conformationally anchored) axial r2-methoxy- trans-4, trans-6-dimethyl- and r-2-cyano- trans-4, trans-6-dimethyl-1,3-dioxanes (1-ax and 3-ax, respectively), the equatorial isomers (2-eq and 4-eq, respectively), the axial r2-methoxy- and r2-cyano- trans-4, trans-6-dimethyl-1,3-dithianes (5-ax and 7-ax, respectively), and the equatorial isomers (6-eq and 8-eq, respectively). The computational results reproduce the anomeric effect in 1-8, and most importantly, Weinhold's NBO analysis supports the contribution of n(X) → σ*(C-Y) stereoelectronic interactions that stabilize the axial isomers. Furthermore, NBO analysis of delocalization energy E(2) of properly aligned filled/empty orbitals in these isomeric 2-polar-substituted heterocycles reveals that n(O) → σ*(C-H ax ) is responsible for the increased charge density at C(2)-H ax in the equatorial isomers, providing an explanation for the computational observation that very recently led Wiberg, Bailey, Lambert, and Stempel ( J. Org. Chem. 2018, 83, 5242-5255) to discard a potential contribution of n(X) → σ*(C-Y) stereoelectronic interactions that stabilize the axial isomers. Interestingly, during the course of this study, two relevant stereoelectronic interactions involving the cyano group were revealed, n(N) → σ*(NC-C) and σ(C(2)-H) → σ*(C-N).

The neurodegenerative disease Friedreich's ataxia is caused by lower than normal levels of frataxin, an important protein involved in iron-sulfur (Fe-S) cluster biogenesis. An important step in designing strategies to treat this disease is to understand whether increasing the frataxin levels by gene therapy would simply be beneficial or detrimental, because previous studies, mostly based on animal models, have reported conflicting results. Here, we have exploited an inducible model, which we developed using the CRISPR/Cas9 methodology, to study the effects of frataxin overexpression in human cells and monitor how the system recovers after overexpression. Using new tools, which range from high-throughput microscopy to in cell infrared, we prove that overexpression of the frataxin gene affects the cellular metabolism. It also leads to a significant increase of oxidative stress and labile iron pool levels. These cellular alterations are similar to those observed when the gene is partly silenced, as occurs in Friedreich's ataxia patients. Our data suggest that the levels of frataxin must be tightly regulated and fine-tuned, with any imbalance leading to oxidative stress and toxicity., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2018. Published by The Company of Biologists Ltd.)

For more than five decades since its original conception, the α-effect has been advocated with arguments based on kinetic reactivity data. The present study was undertaken with the aim of gathering theoretical information on thermodynamic bond energy data in systems that could in principle give rise to intramolecular α-effects. In particular, oxygen-containing six-membered rings oxa-, 1,2-dioxa-, 1,3-dioxa-, 1,2,4-trioxa-, and 1,2,4,5-tetraoxacyclohexane were optimized at the B3LYP/aug-cc-pVTZ level of theory, and the magnitude of all C-H one-bond coupling constants was determined. Furthermore, hyperconjugative interactions were evaluated with Natural Bond Orbital analysis. Analysis of the collected information leads to the conclusion that ether oxygens are apparently better donors than peroxide oxygens; that is, the n(O) → σ*(C-H ax ) two-orbital/two-electron interaction seems to be stronger than the n(O-O) → σ*(C-H ax ) two-orbital/two-electron interaction, and this finding is contrary to expectations in terms of the α-effect.

This paper reports an experimental determination of the gas-phase acidities and basicities of N-benzylalanines, in both their α and β forms, by means of the extended kinetic method (EKM). The experimental gas-phase acidity of β-alanine was also determined. Standard ab initio molecular orbital calculations at the G3 level were performed for alanines, and at the G3(MP2)//B3LYP level for N-benzylalanines. There is a very good agreement between the experimental and the calculated values. The more branched α-amino acids are more acidic and less basic than the linear β-amino acids.

The first systematic study of the intramolecular α-effect, both in the stable ground-state structures and in the high-energy intermediates, was accomplished using the anomeric effect as an internal stereoelectronic probe. Contrary to the expectations based on the simple orbital mixing model, the lone pairs in a pair of neutral directly connected heteroatoms are not raised in energy to become stronger donors toward adjacent σ- and π-acceptors. Instead, the key n (X-Y) →σ* C-F interactions (X,Y = O,N) in the "α-systems" (both acyclic and constrained within a heterocyclohexane frame) are weaker than n X →σ* C-F interactions in "normal" systems. Surprisingly, polar solvent effects increase the apparent magnitude of α-effect as measured via increase in the anomeric stabilization. This behavior is opposite to the solvent dependence of normal systems where the anomeric effect is severely weakened by polar solvents. This contrasting behavior reflects the different balance of electrostatic and conjugative interactions in the two types of anomeric systems: the α-systems suffer less from the unfavorable orientation of bond dipoles in the equatorial conformer, a destabilizing electrostatic effect that is shielded by the polar environments. A weak α-effect is brought to life when the buttressing α-heteroatom bears a negative charge. However, electrostatic components mask the role of stabilizing orbital interactions. In contrast, the increased electron demand in carbocations and related electron-deficient TS- like structures does not lead to activation of the α-effect. As a consequence, we observed that ethers are better radical- and cation-stabilizing groups than peroxides. The latter finding should have significant implications for understanding the mechanistic complexity associated with the interaction of carbonyl compounds with hydroperoxides and H 2 O 2 in acidic media, as such reactions involve α-cationic intermediates.

Background: Neck pain is one of the largest health problems in the military sector., Objective: To assess differences in the strength and endurance of the cervical muscles between military personnel with chronic nonspecific neck pain (CNSNP) with higher level of kinesiophobia (CNSNP-K) and individuals with lower levels of kinesiophobia (CNSNP-NK)., Methods: We used kinesiophobia as a classification method: (1) CNSNP-K and (2) CNSNP-NK. The variables measured were endurance and strength of cervical muscles; range of motion (ROM), disability, pain intensity and psychological factors., Results: Eighty-three military personnel (26 CNSNP-K; 20 CNSNP-NK and 37 asymptomatic). Statistically significant differences in endurance and ROM were only found between the CNSNP-K group and the control group. In strength and disability differences were revealed between both symptomatic groups and the control group [CNSNP-K vs. control (flex-ext p <  0.001); CNSNP-NK vs. control (flex p = 0.003) and (ext p <  0.001)]. For psychological variables, the CNSNP-K group showed differences compared with the CNSNP-NK (pain catastrophizing, p = 0.007; anxiety and depression, p <  0.001) and with the asymptomatic group (pain catastrophizing, p = 0.008; anxiety and depression, p <  0.001)., Conclusions: Military personnel with CNSNP-K have functional limitations and associated psychosocial factors compared with asymptomatic subjects, and showed greater associated psychological factors than CNSNP-NK group. Military personnel with CNSNP-NK only showed decreased strength with respect to those who were asymptomatic.

The electronic states of atmospheric relevant molecules IBr and HgBr 2 are reported, within the UV-Vis spectrum range (170nm≤λ photon ≤600 nm) by means of the complete-active-space self-consistent field/multi-state complete-active-space second-order perturbation theory/spin-orbit restricted-active-space state-interaction (CASSCF/MS-CASPT2/SO-RASSI) quantum-chemical approach and atomic-natural-orbital relativistic-correlation-consistent (ANO-RCC) basis sets. Several analyses of the methodology were carried out in order to reach converged results and therefore to establish a highly accurate level of theory. Good agreement is found with the experimental data with errors not higher than around 0.1 eV. The presented analyses shall allow upcoming studies aimed to accurately determine the absorption cross sections of interhalogen molecules and compounds with Hg that are relevant to better comprehend the photochemical processes taking place in the atmosphere.

In this work we have assessed the ability of a recently proposed three-dimensional integral equation approach to describe the explicit spatial distribution of molecular hydrogen confined in a crystal formed by short-capped nanotubes of C50 H10. To that aim we have resorted to extensive molecular simulation calculations whose results have been compared with our three-dimensional integral equation approximation. We have first tested the ability of a single C50 H10 nanocage for the encapsulation of H2 by means of molecular dynamics simulations, in particular using targeted molecular dynamics to estimate the binding Gibbs energy of a host hydrogen molecule inside the nanocage. Then, we have investigated the adsorption isotherm of the nanocage crystal using grand canonical Monte Carlo simulations in order to evaluate the maximum load of molecular hydrogen. For a packing close to the maximum load explicit hydrogen density maps and density profiles have been determined using molecular dynamics simulations and the three-dimensional Ornstein-Zernike equation with a hypernetted chain closure. In these conditions of extremely tight confinement the theoretical approach has shown to be able to reproduce the three-dimensional structure of the adsorbed fluid with accuracy down to the finest details.

Theoretical calculations on r-1,c-3,c-5-trifluorocyclohexane (1), r-2,c-4,c-6-trifluoro-1,3,5-trioxane (2), and r-2,c-4,c-6-trifluoro-1,3,5-trithiane (3) confirm the importance of n(F) → σ*(C-Y)gem, where Y = H, C, O, S, hyperconjugative interactions; that is, contrary to common wisdom, fluorine is a good lone pair electron donor toward geminal sigma bonds. This conclusion is in line with the recent observations reported by O'Hagan and co-workers, who synthesized and examined all-cis 1,2,3,4,5,6-hexafluoro-cyclohexane (Nat. Chem. 2015, 7, 483-488).

Three decades after the discovery of a strong S-C-P anomeric effect in 2-diphenylphosphinoyl-1,3-dithiane (1) and 2-trimethylphosphonium-1,3-dithiane (4), its definitive interpretation is still lacking. The present study reports DFT geometry optimizations of 1-ax, 1-eq, 4-ax, and 4-eq, which do reproduce the S-C-P anomeric effect in 1 and 4, worth 5.45 and 3.08 kcal/mol, respectively (in chloroform solvent). Weinhold's NBO analysis supports the existence of dominant nX → σ*C-Y stereoelectronic interactions that stabilize the axial conformers.

This paper is concerned with computational and experimental thermochemical studies of azepan and azepan-1-ylacetonitrile, molecules whose flexible ring structure provides several conformational forms with low energy barriers among them. The computational study describes the energetic analysis of the six most stable conformers on the potential energy surfaces and the determination of their gas-phase standard enthalpy of formation at the reference temperature of 298.15 K. The same gas-phase enthalpic parameters are also derived from the enthalpies of formation in the liquid phase and the enthalpies of vaporization, at T = 298.15 K, determined experimentally using the combustion calorimetry and the Calvet microcalorimetry techniques, respectively. The experimental data reported in this work for the two titled compounds together with other available in the literature for related molecules enabled the establishment of an increments scheme, providing a reliable approach on the prevision of gas-phase enthalpy of formation of cyclic/acyclic hydrocarbons and amines. Complementary, natural bond orbital (NBO) calculations were also performed, allowing an advance on the analysis of the structural and reactivity behavior of these type of compounds.

Amino acids play fundamental roles both as building blocks of proteins and as intermediates in metabolism. Proline, one of the 20 natural amino acids, has a primordial function in enzymes, peptide hormones, and proteins. The energetic characterization of these molecules provides information concerning stability and reactivity and has great importance in understanding the activity and behavior of larger molecules containing these structures as fragments. In the present work, parallel experimental and computational studies have been performed. The experimental studies have been based on calorimetric and effusion techniques, from which the enthalpy of formation in the crystalline phase and the enthalpy of sublimation of the sterioisomers L-, D-, and the DL-mixture of proline have been derived. Additionally, vapor pressure measurements have also enabled the determination of the entropies and Gibbs energies of sublimation, at T = 298.15 K. From the former results, the experimental standard (p(o) = 0.1 MPa) molar enthalpies of formation, in the gaseous phase, at T = 298.15 K, of L-proline, D-proline, and DL-proline have been calculated as -388.6 ± 2.3, -391.9 ± 2.0, and -391.5 ± 2.4 kJ·mol(-1), respectively. A computational study at the G3 and G4 levels has been carried out. Conformational analysis has been done and the enthalpy of formation of proline as well as other intrinsic properties such as acidity, basicity, adiabatic ionization enthalpy, electron and proton affinities, and bond dissociation enthalpies have been calculated. There is a very good agreement between calculated and experimental values, when they are available.

Introduction: To evaluate the clinical significance of the isolation of Staphylococcus aureus in urine samples., Methods: A retrospective study was performed on adult patients identified from a microbiology database in a 200-bed general hospital between the years 2000 and 2009. The demographic data, comorbidities, and risk factors, were reviewed, particularly those associated with the concomitant isolation of S.aureus in blood cultures., Results: The frequency of S.aureus found in urine samples was 0.63%. A total of 43 patients (mean age 68.7 years [SD±16], and 58.1% males) were identified in the database. A Charlson comorbidity index >3 was observed in 20.9%. Concurrent bacteremia was seen in 48.8%. Two groups of patients were distinguished: with concomitant bacteremia (n=21) or without (n=22). Intervention in the urinary tract significantly predicted (P=.00004) bacteriuria without bacteremia (81.8%), compared to bacteremia cases (19%). The attributable mortality was 47.6% in patients with bacteremia compared to non-bacteremia (no deaths), even though the appropriate antibiotic treatment was more frequent among patients with bacteremia (92% and 60%, respectively)., Conclusion: The presence of S.aureus in urine was accompanied by bacteremia in half of the cases, but in patients without previous urinary tract intervention such a possibility increased to 81%. Concomitant bacteremia predicts a worse prognosis even with appropriate treatment., (Copyright © 2012 Elsevier España, S.L. All rights reserved.)

A topological analysis of the electron localization function (ELF) of a molecule of hexamethyldisiloxane, (H3C)3-Si-O-Si-(CH3)3, has been carried out, drawing a consistent picture of Si-O-Si bonding both in the linear and angular geometries. The ELF analysis confirms the idea that the O atom, in the linear geometry of (H3C)3-Si-O-Si-(CH3)3, is isolobal with the isoelectronic -CH3(+)- and -BH3- groups, the bonding in the Si-O-Si group being described as a two-electron, three-center (2e, 3c) bond. At the same time, the three oxygen lone pairs mirror the three C-H and B-H bonds, respectively. On the contrary, in the angular geometry the same O atoms form two Si-O bonds and its lone pairs mimic the geometry of the -CH2- group. In this model the O atoms would play the same role as the formally present O(2-) anions in the `so-called' ionic solids, such as in the skeletons of aluminate and silicate polyanions, thereby connecting molecular and solid-state chemistry as formulated by the `fragment formalism' or the `molecular unit-cell approach'. This unifying concept as well as the calculations we have carried out fully agree and also give support to earlier ideas developed by Bragg and Bent, among other authors. Bonding in the series of compounds P4, P4O6, P4O10, N4(CH2)6 (hexamethylenetetramine) and (CH)4(CH2)6 (adamantane) is discussed in the context of the isolobal model.

The formulation of the second-order perturbation approach to the stabilization energy of the A-B interacting species due to charge transfer is revisited. Intrinsic (i.e., electronic) theoretical indices for both relative electrophilicity and nucleophilicity are proposed for any electrophile (A)-nucleophile (B) pairs of combining species. By using the new descriptors, an electronic analogue to the Mayr-Patz linear free relationship has been successfully tested in the context of available experimental evidence reported for reactions of primary and secondary amines with benzhydrylium ions.

Solanum nudum Dunal steroids have been reported as being antimalarial compounds; however, their concentration in plants is low, meaning that the species could be threatened by over-harvesting for this purpose. Swern oxidation was used for hemisynthesis of diosgenone (one of the most active steroidal sapogenin diosgenin compounds). Eighteen structural analogues were prepared; three of them were found to be more active than diosgenone (IC50 27.9 μM vs. 10.1 μM, 2.9 μM and 11.3 μM). The presence of a 4-en-3-one grouping in the A-ring of the compounds seems to be indispensable for antiplasmodial activity; progesterone (having the same functional group in the steroid A-ring) has also displayed antiplasmodial activity. Quantitative correlations between molecular structure and bioactivity were thus explored in diosgenone and several derivatives using well-established 3D-QSAR techniques. The models showed that combining electrostatic (70%) and steric (30%) fields can explain most variance regarding compound activity. Malarial parasitemia in mice became reduced by oral administration of two diosgenone derivatives.

We describe in the current paper an experimental and computational study of three methylated uracils, in particular, the 5,6-dimethyl-, 1,3,5-trimethyl-, and 1,3,5,6-tetramethyl derivatives. The values of the standard (p(0) = 0.1 MPa) molar enthalpies of formation in the gas phase at T = 298.15 K have been determined. The energies of combustion were measured by static bomb combustion calorimetry, and from the results obtained, the standard molar enthalpies of formation in the crystalline state at T = 298.15 K were calculated. The enthalpies of sublimation were determined using the transpiration method in a saturated N(2) stream. Values of -(376.2 ± 2.6), -(355.9 ± 3.0), and -(381.7 ± 2.8) kJ·mol(-1) for the gas-phase enthalpies of formation at T = 298.15 K of 5,6-dimethyluracil, 1,3,5-trimethyluracil, and 1,3,5,6-tetramethyluracil, respectively, were obtained from the experimental thermochemical study. An extended theoretical study with the G3 and the G4 quantum-chemical methods has been carried out for all the possible methylated uracils. There is a very good agreement between experimental and calculated enthalpies of formation for the three derivatives studied. A Free-Wilson analysis on G4-calculated enthalpies of formation has been carried out, and the contribution of methylation in the different positions of the uracil ring has been estimated.