Computational Study of Copper(II) Complexation and Hydrolysis in Aqueous Solutions Using Mixed Cluster/Continuum Models

We use density functional theory (B3LYP) and the COSMO continuum solvent model to characterize the structure and stability of the hydrated Cu(II) complexes [Cu(MeNH_2)(H_2O)_(n−1)]^(2+) and [Cu(OH)_x(H_2O)_(n−x)]^(2−x) (x = 1−3) as a function of metal coordination number (4−6) and cluster size (n = 4−8, 18). The small clusters with n = 4−8 are found to be the most stable in the nearly square-planar four-coordinate configuration, except for [Cu(OH)_3(H_2O)]^−, which is three-coordinate. In the presence of the two full hydration shells (n = 18), however, the five-coordinate square-pyramidal geometry is the most favorable for Cu(MeNH_2)^(2+) (5, 6) and Cu(OH)^+ (5, 4, 6), and the four-coordinate geometry is the most stable for Cu(OH)_2 (4, 5) and Cu(OH)_3^− (4). (Other possible coordination numbers for these complexes in the aqueous phase are shown in parentheses.) A small energetic difference between these structures (0.23−2.65 kcal/mol) suggests that complexes with different coordination numbers may coexist in solution. Using two full hydration shells around the Cu^(2+) ion (18 ligands) gives Gibbs free energies of aqueous reactions that are in excellent agreement with experiment. The mean unsigned error is 0.7 kcal/mol for the three consecutive hydrolysis steps of Cu^(2+) and the complexation of Cu^(2+) with methylamine. Conversely, calculations for the complexes with only one coordination shell (four equatorial ligands) lead to a mean unsigned error that is >6.0 kcal/mol. Thus, the explicit treatment of the first and the second shells is critical for the accurate prediction of structural and thermodynamic properties of Cu(II) species in aqueous solution

Evaluation of B3LYP, X3LYP, and M06-class density functionals for predicting the binding energies of neutral, protonated, and deprotonated water clusters

In this paper we assess the accuracy of the B3LYP, X3LYP, and newly developed M06-L, M06-2X, and M06 functionals to predict the binding energies of neutral and charged water clusters including (H_2O)_n, n = 2−8, 20), H_3O+(H_2O_)n, n = 1−6, and OH−(H_2O)_n, n = 1−6. We also compare the predicted energies of two ion hydration and neutralization reactions on the basis of the calculated binding energies. In all cases, we use as benchmarks calculated binding energies of water clusters extrapolated to the complete basis set limit of the second-order Møller−Plesset perturbation theory with the effects of higher order correlation estimated at the coupled-cluster theory with single, double, and perturbative triple excitations in the aug-cc-pVDZ basis set. We rank the accuracy of the functionals on the basis of the mean unsigned error (MUE) between calculated benchmark and density functional theory energies. The corresponding MUE (kcal/mol) for each functional is listed in parentheses. We find that M06-L (0.73) and M06 (0.84) give the most accurate binding energies using very extended basis sets such as aug-cc-pV5Z. For more affordable basis sets, the best methods for predicting the binding energies of water clusters are M06-L/aug-cc-pVTZ (1.24), B3LYP/6-311++G(2d,2p) (1.29), and M06/aug-cc-PVTZ (1.33). M06-L/aug-cc-pVTZ also gives more accurate energies for the neutralization reactions (1.38), whereas B3LYP/6-311++G(2d,2p) gives more accurate energies for the ion hydration reactions (1.69)

Surgical intervention on uterine fibromyoma in a country with limited resources: case of the gynaecology-obstetrics department of the Communal Medical Centre of Ratoma Conakry - Guinea

Background: In developing countries, treatment of uterine fibromyoma is confronted with numerous problems, namely: financial inaccessibility to the proposed treatments, fear of surgery and the weakness of the technical platform. The objectives of the study were to calculate the frequency of uterine fibromyomas, describe the socio-demographic characteristics of patients, identify the main clinical data and to describe the modalities of surgical management.Methods: It was a mixed descriptive study, cumulative over a period of 5 years (60 months) with data collection in two phases: a 4-year retrospective study from January 1, 2015 to December 31, 2018 and a 1-year prospective study from January 1, 2019 to December 31, 2019.Results: Authors collected 135 cases of uterine fibromyomas operated on out of a total of 260 cases of gynaecological pathologies, i.e. a frequency of 51.92%. Nulliparous women were the most concerned (45.18%), and women who attended school (60%) and those who did not attend school (40%). Women at home and housewives accounted for 42.20% and 54.07% respectively. Clinically, the circumstances of discovery were dominated by menometrorrhagia and menorrhagia respectively 77.77% and 68.14%. The large uterus was the most frequent physical sign found in 96.29% of cases. Uterine fibromyomas were recorded in 86.6% of cases in women with genital activity. The operative indications were dominated by the large polymyomatous uterus (64.44%), followed by hemorrhagic fibroma (18.52%) The surgical treatment was conservative in 92.60%. The total hysterectomy was performed in 7.40. Lethality was 1.4%.Conclusions: The surgical management of fibroids contrasts conservative treatment (myomectomy) with radical treatment (hysterectomy) with multiple possible approaches (hysteroscopy, vaginal surgery, laparoscopy or laparotomy). In this context, only laparotomy was possible due to lack of equipment. Laparoscopy and hysteroscopy equipment are necessary for less invasive surgery

pK_a Calculations of Aliphatic Amines, Diamines, and Aminoamides via Density Functional Theory with a Poisson−Boltzmann Continuum Solvent Model

In order to make reliable predictions of the acid−base properties of macroligands with a large number of ionizable sites such as dendrimers, one needs to develop and validate computational methods that accurately estimate the acidity constants (pK_a) of their chemical building blocks. In this article, we couple density functional theory (B3LYP) with a Poisson−Boltzmann continuum solvent model to calculate the aqueous pK_a of aliphatic amines, diamines, and aminoamides, which are building blocks for several classes of dendrimers. No empirical correction terms were employed in the calculations except for the free energy of solvation of the proton (H^+) adjusted to give the best match with experimental data. The use of solution-phase optimized geometries gives calculated pK_a values in excellent agreement with experimental measurements. The mean absolute error is 0.5 pK_a unit compared to experimental measurements. We find that geometry optimization in solution is essential for making accurate pK_a predictions for systems possessing intramolecular hydrogen bonds

Partitioning of Poly(amidoamine) Dendrimers between n-Octanol and Water

Dendritic nanomaterials are emerging as key building blocks for a variety of nanoscale materials and technologies. Poly(amidoamine) (PAMAM) dendrimers were the first class of dendritic nanomaterials to be commercialized. Despite numerous investigations, the environmental fate, transport, and toxicity of PAMAM dendrimers is still not well understood. As a first step toward the characterization of the environmental behavior of dendrimers in aquatic systems, we measured the octanol−water partition coefficients (logK_(ow)) of a homologous series of PAMAM dendrimers as a function of dendrimer generation (size), terminal group and core chemistry. We find that the logKow of PAMAM dendrimers depend primarily on their size and terminal group chemistry. For G1-G5 PAMAM dendrimers with terminal NH_2 groups, the negative values of their logK_(ow) indicate that they prefer to remain in the water phase. Conversely, the formation of stable emulsions at the octanol−water (O/W) interface in the presence of G6-NH_2 and G8-NH_2 PAMAM dendrimers suggest they prefer to partition at the O/W interface. In all cases, published studies of the cytotoxicity of Gx-NH_2 PAMAM dendrimers show they strongly interact with the lipid bilayers of cells. These results suggest that the logKow of a PAMAM dendrimer may not be a good predictor of its affinity with natural organic media such as the lipid bilayers of cell membranes

Prophylactic and emergency cesareans: a comparative study on 718 observations at the maternity ward of Ignace Deen National hospital

Background: The objective of the study is to compare the frequency, the socio-demographic characteristics, the indications, the fetal maternal prognosis and the Robson classification of prophylactic and emergency caesarean sections.Methods: This was a comparative study of prophylactic and emergency caesarean sections at the maternity of Ignace Deen national hospital. It was a 12 month (July 1, 2016 to June 30, 2017) descriptive and analytical study.Results: Prophylactic caesarean sections accounted for 12, 51% of caesarean sections and 3.96% of deliveries at the ward. Prophylactic caesarean sections involved pregnant women aged from 20 to 29, holder of higher education degrees (51.54%), married (92.76%) employed (56.83%) and whose prenatal visit was provided by the obstetrician (73.54%). While the emergency caesarean section concerned parturient aged between 20 and 34, mostly non-schooled (36.49%), transferred patients (80.22%) and nulliparous (58.5%). Surgical indications were mainly scarred uterus (32.32%) and maternal pathologies (18.11%) prophylaxis; bleeding in the last quarter (25.90%) acute fetal distress (20.33%) in emergency. Groups 6 and 5 of the Robson classification were the most represented with a 2.23% morbidity and a zero maternal lethality in prophylaxis versus groups 5 and 6 with a 10.03% morbidity and a 1.67% maternal lethality in emergency.Conclusions: Improving this prognosis would be achieved through an increase in the frequency of prophylactic caesarean sections

Interactions of Poly(amidoamine) Dendrimers with Human Serum Albumin: Binding Constants and Mechanisms

The interactions of nanomaterials with plasma proteins have a significant impact on their in vivo transport and fate in biological fluids. This article discusses the binding of human serum albumin (HSA) to poly(amidoamine) [PAMAM] dendrimers. We use protein-coated silica particles to measure the HSA binding constants (K_b) of a homologous series of 19 PAMAM dendrimers in aqueous solutions at physiological pH (7.4) as a function of dendrimer generation, terminal group, and core chemistry. To gain insight into the mechanisms of HSA binding to PAMAM dendrimers, we combined ^1H NMR, saturation transfer difference (STD) NMR, and NMR diffusion ordered spectroscopy (DOSY) of dendrimer−HSA complexes with atomistic molecular dynamics (MD) simulations of dendrimer conformation in aqueous solutions. The binding measurements show that the HSA binding constants (K_b) of PAMAM dendrimers depend on dendrimer size and terminal group chemistry. The NMR ^1H and DOSY experiments indicate that the interactions between HSA and PAMAM dendrimers are relatively weak. The ^1H NMR STD experiments and MD simulations suggest that the inner shell protons of the dendrimers groups interact more strongly with HSA proteins. These interactions, which are consistently observed for different dendrimer generations (G0-NH_2vs G4-NH_2) and terminal groups (G4-NH_2vs G4-OH with amidoethanol groups), suggest that PAMAM dendrimers adopt backfolded configurations as they form weak complexes with HSA proteins in aqueous solutions at physiological pH (7.4)

Addition of H_2O and O_2 to Acetone and Dimethylsulfoxide Ligated Uranyl(V) Dioxocations

Gas-phase complexes of the formula [UO_2(lig)]^+ (lig = acetone (aco) or dimethylsulfoxide (dmso)) were generated by electrospray ionization (ESI) and studied by tandem ion-trap mass spectrometry to determine the general effect of ligand charge donation on the reactivity of UO_2^+ with respect to water and dioxygen. The original hypothesis that addition of O_2 is enhanced by strong σ-donor ligands bound to UO_2^+ is supported by results from competitive collision-induced dissociation (CID) experiments, which show near exclusive loss of H_2O from [UO_2(dmso)(H_2O)(O_2)]^+, whereas both H_2O and O_2 are eliminated from the corresponding [UO_2(aco)(H_2O)(O_2)]^+ species. Ligand-addition reaction rates were investigated by monitoring precursor and product ion intensities as a function of ion storage time in the ion-trap mass spectrometer: these experiments suggest that the association of dioxygen to the UO_2^+ complex is enhanced when the more basic dmso ligand was coordinated to the metal complex. Conversely, addition of H_2O is favored for the analogous complex ion that contains an aco ligand. Experimental rate measurements are supported by density function theory calculations of relative energies, which show stronger bonds between UO_2^+ and O_2 when dmso is the coordinating ligand, whereas bonds to H_2O are stronger for the aco complex