Alterations of Nutritional Status in Children and Adolescents with Acute Lymphoblastic Leukemia.

Malnutrition is often observed in pediatric cancer patients and has been recognized as a risk factor for relapse and survival. Maintaining an appropriate nutritional status during anticancer treatment has, therefore, been more and more frequently perceived as an additional requirement for optimal therapy outcomes. The aim of our study was to establish alterations of nutritional status in 26 children and adolescents treated for acute lymphoblastic leukemia (ALL) at the Children's Hospital in Zagreb, Croatia, between 2016 and 2021, by using anthropometric measures and serum albumin levels. The majority of patients (53.8% female, median 4 years, 52.2% intermediate-risk leukemia group) had normal weight at the beginning of chemotherapy. The percentage of overweight/obese patients increased from 4.2% at diagnosis to 37.5% at the end of intensive therapy. Apart from a significant increase in body weight (BW) and body mass index (BMI) for age, a notable decline in body height/body length (BH/BL) for age in the observed period was recorded, especially in high-risk leukemia patients. The alterations in serum albumin values were not significant, nor was their correlation with BMI. Dietary consultation was offered to all patients, while children with a decline in BMI and BH/BL received additional nutritional support.

Bacteriuria in Paediatric Oncology Patients: Clinical Features, Distribution and Antimicrobial Susceptibility of Bacterial Pathogens at University Hospital Centre Zagreb, Croatia over a 4-Year Period.

Bacteriuria in paediatric oncology patients have not been well studied. This retrospective study analysed clinical features, distribution and antimicrobial susceptibility of bacterial pathogens cultured from urine in paediatric oncology patients over a 4-year period (2019-2022). A total of 143 episodes of bacteriuria were documented in 74 patients. Neutropenia was present in 17.5% (25/143), symptoms in 25.9% (37/143) and urinary catheter in 7.0% (10/143) episodes. Symptomatic bacteriuria episodes were statistically significantly more frequent in patients with neutropenia (p = 0.0232). The most common bacterial pathogens were Escherichia coli (n = 49; 32.2%), Klebsiella spp. (n = 34; 22.4%), Pseudomonas aeruginosa (n = 22; 14.5%) and Enterococcus spp. (n = 21; 13.8%). Extended-spectrum ß-lactamases-producing (ESBL) Enterobacterales were found in 11 episodes (11/143; 7.7%) with the highest proportion among Klebsiella pneumoniae isolates (n = 7/34; 20.6%). No carbapenem-resistant Enterobacterales, multidrug-resistant P. aeruginosa or vancomycin-resistant Enterococcus spp. were found. The most important novelties are demonstrating P. aeruginosa as one of the prominent bacteriuria pathogens in this patient population, presence of ESBL isolates and carbapenem-resistant P. aeruginosa later during hospitalization highlights the need for appropriate antimicrobial treatment. However, because of the small number of symptomatic patients, further studies are needed to clarify the importance of including urine culture in the diagnostic process in patients with febrile neutropenia.

Bloodstream Infections in Pediatric Oncology Patients: Bacterial Pathogen Distribution and Antimicrobial Susceptibility at the University Hospital Centre Zagreb, Croatia-A 5-Year Analysis.

The epidemiology of bacterial pathogens causing bloodstream infections (BSIs) in pediatric hematology/oncology patients is changing and resistance to antimicrobial agents is globally spread. We retrospectively assessed demographic, clinical, and microbiologic data of BSIs during a 5-year period at a pediatric hematology/oncology unit from January 1, 2017, to December 31, 2021, at the University Hospital Centre Zagreb, Zagreb, Croatia. In 66 pediatric patients with malignancies, 93 BSI episodes were registered and 97 bacterial isolates were cultured. The Gram-positive versus Gram-negative ratio was 67 (69.1%) versus 30 (30.9%). Coagulase-negative staphylococci (48; 49.6%) were the most frequent isolates, followed by Enterobacterales (17; 17.5%) and Staphylococcus aureus (6; 6.2%). Multidrug resistance isolates included extended spectrum ß-lactamase producers (n=3). Resistance rates to piperacillin/tazobactam, cefepime, and meropenem in Gram-negative isolates were 15.4%, 14.3%, and 0.0%, respectively. Gram-positive bacteria are the most common cause of BSI in our patients. Resistance rates to piperacillin/tazobactam and cefepime in Gram-negative isolates make meropenem a better choice for empirical antimicrobial treatment. As national and hospital data may differ, the surveillance of pathogen distribution and antimicrobial susceptibility in pediatric hematology/oncology wards is necessary to adjust empirical treatment accordingly.

Management of Childhood Iron Deficiency Anemia in a Developed Country-A Multi-Center Experience from Croatia.

Iron deficiency anemia (IDA) continues to be a global public health concern, mostly in the developing countries. However, precise epidemiological data on childhood IDA in Croatia are lacking. In order to establish its frequency, underlying etiologies, the rationale for tertiary care visits, diagnostic practices, and current treatment regimens of IDA, medical records of children referred to pediatric hematologists for iron deficiency in a five-year period at tertiary institutions (Zagreb, Rijeka, Split, Osijek) throughout Croatia were retrospectively analyzed. Eight hundred and sixty-four children, predominately of preschool age, were referred mainly by the primary care pediatricians, who, in general, performed basic diagnostics but failed to initiate oral iron therapy in half of the patients. Approximately one-third of patients were symptomatic, with inadequate nutrition prevailing as underlying etiology. Dextriferron was the preferred iron formulation among hematologists, with a median dose of 5 mg/kg, with acceptable compliance rates (63.5-93.2%). Hospital admission rates varied among the centers (9.4-35%), and so did transfusion policies (6.4-22.9%). The greatest difference was observed in the frequency of parenteral iron administration (0.3-21.5%). In conclusion, the burden of childhood IDA, even in a high-income country, remains substantial, necessitating consistent implementation of national guidelines and additional education of primary health care providers.

Retroperitoneal Paraganglioma Treated With Tumor Resection and Replacement of the Inferior Vena Cava.

Retroperitoneal paragangliomas are tumors of neuroectodermal origin rarely appearing in the pediatric population. We report a case of a large paraganglioma infiltrating the right kidney and inferior vena cava in a 16-year-old boy who initially presented with a right-sided varicocele. Right retroperitoneal paraganglioma was embolized preoperatively, followed by total tumor excision, right nephrectomy, inferior vena cava resection, and reconstruction using a prosthetic vascular graft. Retroperitoneal tumors requiring surgery can successfully be treated by radical resection and replacement of the inferior vena cava in experienced centers.

Case report: Autoimmune hemolytic anemia caused by warm and cold autoantibodies with complement activation-etiological and therapeutic issues.

Introduction: Research on mixed warm and cold autoantibodies in autoimmune hemolytic anemia (AIHA) targeting erythrocytes [red blood cells (RBCs)] and platelets is scarcely reported. Case presentation: In this study, we present the case of a 5-year-old boy with positive direct [anti-IgG (1+), anti-IgG-C3d (3+)], and indirect antiglobulin (Coombs) tests. The RBCs were coated with polyspecific-positive, warm IgG autoantibodies alongside activated complement components. Plasma-containing immunoglobulin M (IgM) class autoantibodies were found in 1:64 titers with a wide temperature range of 4°C-37°C. The platelets were also coated with IgM autoantibodies. There was a reduction in the levels of the classical and alternative complement pathways, such as C3, C4, ADAMTS13 metalloprotease activity, factor H antigen, complement factor B antigen, and C1q antigen alongside the elevated sC5b-9 terminal complement complex. Hematuria and/or proteinuria, reduced diuresis, and elevated levels of serum creatinine were absent. The kidney ultrasound report was normal. A recent combination of Epstein-Barr virus (EBV) and cytomegalovirus (CMV) infection was found. The first-line treatment consisted of intravenous methylprednisolone [4 mg/kg/body weight for the first 72 h (q12 h), followed by 2 mg/kg body weight for 21 consecutive days with a slow steroid reduction until plasmapheresis (PLEX)]. After the patient showed limited response to corticosteroid therapy, rituximab (375 mg/m2) was administered once a week (five doses in total), with vitamins B9 and B12. These strategies also showed limited (partial) therapeutic benefits. Therefore, the treatment was switched to PLEX (five cycles in total) and intravenous immunoglobulin (IVIg) (1 g/kg/5 days). This combination significantly improved RBC count and platelet levels, and C3 and C4 levels returned to normal. A follow-up of 2.5 years after treatment showed no sign of relapse. A genetic analysis revealed a rare heterozygous intronic variation (c.600-14C > T) and heterozygous Y402H polymorphism of the CFH gene. c.600-14C > T mutation was located near the 5' end of exon 6 in the gene encoding the complement C3 protein of unknown significance. We presumed that the complement regulators in our patient were sufficient to control complement activation and that complement blockade should be reserved only for devastating, life-threatening complement-related multiorgan failure. Conclusion: We believe that EBV and CMV triggered AIHA, thus activating the complement cascade. Hence, we used corticosteroids, rituximab, vitamins B9 + B12, PLEX, and fresh frozen plasma (FFP) as treatment. Final remission was achieved with PLEX and FFP. However, an additional late effect of B12 rituximab and the disappearance of long-lived circulating plasma cells should not be completely ignored. Complement activation with a genetic background should be assessed in severe warm and cold hemolytic anemias caused by autoantibodies.

Evaluation of a multimodal pain therapy approach with relapse prophylaxis for back pain (MMS-RFP study): a study protocol for a cluster randomised controlled trial.

INTRODUCTION: The need for an interdisciplinary multimodal approach to the treatment of back pain has already been demonstrated by various studies. However, when considering the periods of incapacity to work in the longitudinal course after the multimodal pain therapy (MPT), limits in terms of its sustainable effect become clear. Patients who receive MPT subsequently return to standard outpatient care, which is associated with a risk of relapse. A 12-month relapse prophylaxis (RP) programme, intended to follow a 4-week MPT, was developed to help patients make the transition to health-conscious and physically active behaviour in everyday life and to identify and prevent impending relapses at an early stage. The evaluation, based on a cluster randomised controlled trial, seeks to provide information on the benefits of early and intensive RP as part of MPT, examine whether it is cost effective, reduces the days of incapacity to work and increases functional capacity, as well as to examine other parameters. METHODS AND ANALYSIS: The study population comprises members of a regional statutory health insurance fund in Germany, who are ≤62 years old, gainfully employed and have been incapacitated for work for at least 21 days due to a diagnosis of back pain. Over a recruitment period of 24 months, a maximum of 368 individuals can potentially be included in the MPT. The intervention group (IG) and control group (CG) will both receive MPT, after randomisation IG will receive RP and CG will receive no further therapy or support as part of the trial. The evaluation is carried out on the following levels: structural, process and results quality. Cost effectiveness is also assessed by means of a health economic evaluation. In addition to the collection of qualitative and quantitative primary data, claims data from the regional health insurance fund are also included in the analysis. ETHICS AND DISSEMINATION: This study has received approval by the ethics committee of the Hannover Medical School (reference number: 8548_BO_S_2019). The study results will be disseminated in national and international journals and conference presentations. TRIAL REGISTRATION NUMBER: DRKS00017654.

Circadian desynchrony disturbs the function of rat spermatozoa.

Decreased male fertility is a growing health problem that requires a better understanding of molecular events regulating reproductive competence. Here the effects of circadian desynchrony on the rat spermatozoa functionality were studied. Circadian desynchrony was induced in rats that lived for 2 months under disturbed light conditions designed to mimic shiftwork in humans (two days of constant light, two days of continual dark, and three days of 14:10 h light:dark schedule). Such a condition abolished circadian oscillations in the rats' voluntary activity, followed by a flattened transcriptional pattern of the pituitary gene encoding follicle stimulating hormone subunit (Fshb), and genes important for germ cell maturation (Tnp1 and Prm2) as well as the clock in seminiferous tubules. However, the number of spermatozoa isolated from the epididymis of the rats suffering from circadian desynchrony did not deviate from the controls. Nevertheless, spermatozoa functionality, estimated by motility and progesterone-induced acrosome reaction, was reduced compared to the control. These changes were associated with the altered level of main markers of mitochondrial biogenesis (Pprgc1a/PGC1A, Nrf1/NRF1, Tfam, Cytc), decreased mitochondrial DNA copy number, ATP content, and clock genes (Bmal1/BMAL1, Clock, Cry1/2, and Reverba). The principal-component-analysis (PCA) points to a positive association of the clock and mitochondrial biogenesis-related genes in spermatozoa from rats suffering circadian desynchrony. Altogether, the results show the harmful effect of circadian desynchrony on spermatozoa functionality, targeting energetic homeostasis.

The cost of the circadian desynchrony on the Leydig cell function.

The increased frequency of different lifestyles that disrupts circadian rhythms, together with a trend in the accretion of male idiopathic infertility, imposes the necessity to understand the contribution of circadian rhythms disruption to fertility regulation. In this study, the effects of circadian desynchrony (CD) on the steroidogenic capacity of adult Leydig cells were studied. Adult rats were housed under a disturbing light regime (2 days of constant light, 2 days of continual dark, and 3 days of 12:12 h light:dark schedule) designed to mimic shiftwork in humans. CD was characterized by changed and decreased rhythmic locomotor activity and reduced blood testosterone. In the Leydig cells changed transcription of the clock genes (Bmal1, Clock, Cry1 and Reverba/b increased while Per1/2 reversed phase) was detected. This was followed by reduced transcription of genes (Star, Cyp11a1, and Hsd3b1/2) primarily involved in mitosteroidogenesis. In parallel, mitochondrial membrane potential (Δψi) and ATP production declined losing their characteristic oscillatory pattern. Also, the main markers of mitochondrial biogenesis (Ppargc1a, Nrf1, Tfam, Cytc), fusion (Mfn2), and mitophagy (Pink1 and Tfeb) were disturbed. Collectively, CD targets mitochondria in Leydig cells by reducing mitosteroidogenesis, mitoenergetics, and disturbing mitochondrial dynamics. These changes contribute to testosterone decline compromising androgen-dependent functions, including reproduction.

Probable Bruxism and Psychological Issues among Dental Students in Serbia during the COVID-19 Pandemic.

The COVID-19 pandemic has drastically changed the routine way of life, having consequences in many segments of life, including dental practice and education. The aim of this study was to evaluate the frequency of probable bruxism in a sample of dental students in Serbia and to estimate the potential association between psychological factors related to the COVID-19 pandemic and the presence of bruxism. A cross-sectional study included 178 dental students in Serbia, who were interviewed using a specially-designed self-administered online questionnaire, which consisted of three sections, and after that, a clinical examination for the presence of bruxism symptoms in the oral cavity. Psychological status was evaluated using the Depression, Anxiety and Stress Scale-21 (DASS-21) and the Fear of COVID-19 Scale (FCV-19S). Saliva samples were taken to analyze salivary cortisol levels. The prevalence of probable bruxism was 34.8%. Respondents with probable bruxism had significantly higher DASS-21 and FCV-19S scores and mean values of salivary cortisol compared to non-bruxers. A history of COVID-19 infection, high stress, and fear of COVID-19 scores were associated with the presence of probable bruxism. The findings suggest that the COVID-19 pandemic has had a great psychological impact and impact on the presence and worsening of bruxism symptoms in a sample of dental students in Serbia.

Analysis of the Impact of Oral Health on Adolescent Quality of Life Using Standard Statistical Methods and Artificial Intelligence Algorithms.

The aim of this study was to determine the impact of oral health on adolescent quality of life and to compare the results obtained using standard statistical methods and artificial intelligence algorithms. In order to measure the impact of oral health on adolescent quality of life, a validated Serbian version of the Oral Impacts on Daily Performance (OIDP) scale was used. The total sample comprised 374 respondents. The obtained results were processed using standard statistical methods and machine learning, i.e., artificial intelligence algorithms-singular value decomposition. OIDP score was dichotomized into two categories depending on whether the respondents had or did not have oral or teeth problems affecting their life quality. Human intuition and machine algorithms came to the same conclusion on how the respondents should be divided. As such, method quality and the need to perform analyses of this type in dentistry studies were demonstrated. Using artificial intelligence algorithms, the respondents can be clustered into characteristic groups that allow the discovery of details not possible with the intuitive division of respondents by gender.

Immunohistochemical expression of cyclin-dependent kinase inhibitors p16 and p57 in rhabdomyosarcoma.

Rhabdomyosarcoma (RMS) is a highly malignant cancer and is the most common soft tissue sarcoma in children and adolescents, but it is rare in adults (<1% of all adult malignancies). Altered expression and molecular abnormalities of cell-cycle-regulatory proteins are one of the most prominent features in RMS. Therefore, we evaluated the expression of cyclin-dependent kinase inhibitors p57 and p16, as well as p16 methylation status, along with clinicopathological characteristics and overall survival (OS) in RMS patients. This analysis was conducted on 23 pediatric and 44 adult patients. There was a male predominance in both groups and extremities were the most frequent tumor site. In adults, alveolar and pleomorphic types were almost equally represented. The majority of pediatric tumors were low grade, whereas, in adults, only one patient had a low-grade tumor. Seven pediatric (30.43%) and eight adult (18.18%) patients had a low p16 expression. The analysis of methylation status of the p16 promoter showed the presence of methylated allele only in one sample with pleomorphic histology. Six (26.1%) pediatric and 15 (34.1%) adult patients had low p57 expression, while in 17 (73.9%) pediatric and 29 (65.9%) adult patients it was assessed as high. Ninetyone percent of the pediatric patients and 32.6% of adults were alive at the end of the observational period. In adults, significant associations were found between OS and age (P = 0.020), gender (P = 0.027), tumor size (P < 0.001), lymph node status (P < 0.001), presence of metastases (P = 0.015), and p57 expression (P = 0.039). Stratification by histological type showed the correlation of low p57 expression (P = 0.030) and worse OS of patients with alveolar RMS. Univariate analysis identified age > 50 yrs. (HR 2.447), tumors > 5 cm (HR 21.31), involvement of regional lymph nodes (HR 3.96), the presence of metastases (HR 2.53), and low p57 expression (HR 2.11) as predictors of lower OS. Tumor size, regional lymph nodes involvement, and metastases were the independent predictors after multivariate analysis, while p57 did not predict OS in an independent way. In summary, although p57 was not confirmed to be an independent predictor of OS, our results indicate that its low expression may be the marker of aggressive phenotype and poor prognosis in adult RMS patients. Also, our findings suggest that epigenetic inactivation of p16 is not important in the pathogenesis of rhabdomyosarcoma.

Low cardiac output syndrome requiring extracorporeal membrane oxygenation following pericardiocentesis in an adolescent with Hodgkin Lymphoma: a case report.

We present a case of a 16-year-old male with large pericardial effusion due to Hodgkin Lymphoma (HL). Shortly after drainage of pericardial effusion he developed a low cardiac output syndrome which had to be treated with extracorporeal membrane oxygenation (ECMO). This 9-day ECMO support helped the patient to recover his cardiac function, and thereafter a remission of his primary disease was successfully achieved with chemotherapy. It is a matter of discussion whether a large pericardial effusion with moderate symptoms in patients with HL should be evacuated or just observed since the effusion should ameliorate with chemotherapy. But based upon our experience in this case of hemodynamic instability due to a large effusion requiring evacuation, we propose that pericardiocentesis procedure should be performed with caution at a slow drainage rate of 0.5-1 ml/kg/hour with a maximum rate of 50 ml/hour, to help avoid the low cardiac output syndrome in patients with similar disease conditions.

Unique mononuclear Mn(II) complexes of an end-off compartmental Schiff base ligand: experimental and theoretical studies on their bio-relevant catalytic promiscuity.

Three new mononuclear manganese(ii) complexes, namely [Mn(HL)2]·2ClO4 (1), [Mn(HL)(N(CN)2)(H2O)2]·ClO4 (2) and [Mn(HL)(SCN)2] (3) [LH = 4-tert-butyl-2,6-bis-[(2-pyridin-2-yl-ethylimino)-methyl]-phenol], have been synthesized and structurally characterized. An "end-off" compartmental ligand (LH) possesses two symmetrical compartments with N2O binding sites but accommodates only one manganese atom instead of two due to the protonation of the imine nitrogen of one compartment. Although all three complexes are mononuclear, complex 1 is unique as it has a 1 : 2 metal to ligand stoichiometry. The catalytic promiscuity of complexes 1-3 in terms of two different bio-relevant catalytic activities namely catecholase and phenoxazinone synthase has been thoroughly investigated. EPR and cyclic voltametric studies reveal that radical formation rather than metal centered redox participation is responsible for their catecholase-like and phenoxazinone synthase-like catalytic activity. A computational approach suggests that imine bond bound radical generation rather than phenoxo radical formation is most likely responsible for the oxidizing properties of the complexes.

Assessment of TD-DFT and LF-DFT for study of d - d transitions in first row transition metal hexaaqua complexes.

Herein, we present the systematic, comparative computational study of the d - d transitions in a series of first row transition metal hexaaqua complexes, [M(H2O)6](n+) (M(2+/3+) = V (2+/3+), Cr(2+/3+), Mn(2+/3+), Fe(2+/3+), Co(2+/3+), Ni(2+)) by the means of Time-dependent Density Functional Theory (TD-DFT) and Ligand Field Density Functional Theory (LF-DFT). Influence of various exchange-correlation (XC) approximations have been studied, and results have been compared to the experimental transition energies, as well as, to the previous high-level ab initio calculations. TD-DFT gives satisfactory results in the cases of d(2), d(4), and low-spin d(6) complexes, but fails in the cases when transitions depend only on the ligand field splitting, and for states with strong character of double excitation. LF-DFT, as a non-empirical approach to the ligand field theory, takes into account in a balanced way both dynamic and non-dynamic correlation effects and hence accurately describes the multiplets of transition metal complexes, even in difficult cases such as sextet-quartet splitting in d(5) complexes. Use of the XC functionals designed for the accurate description of the spin-state splitting, e.g., OPBE, OPBE0, or SSB-D, is found to be crucial for proper prediction of the spin-forbidden excitations by LF-DFT. It is shown that LF-DFT is a valuable alternative to both TD-DFT and ab initio methods.

Magnetic anisotropy in "scorpionate" first-row transition-metal complexes: a theoretical investigation.

In this work we have analyzed in detail the magnetic anisotropy in a series of hydrotris(pyrazolyl)borate (Tp(-)) metal complexes, namely [VTpCl](+), [CrTpCl](+), [MnTpCl](+), [FeTpCl], [CoTpCl], and [NiTpCl], and their substituted methyl and tert-butyl analogues with the goal of observing the effect of the ligand field on the magnetic properties. In the [VTpCl](+), [CrTpCl](+), [CoTpCl], and [NiTpCl] complexes, the magnetic anisotropy arises as a consequence of out-of-state spin-orbit coupling, and covalent changes induced by the substitution of hydrogen atoms on the pyrazolyl rings does not lead to drastic changes in the magnetic anisotropy. On the other hand, much larger magnetic anisotropies were predicted in complexes displaying a degenerate ground state, namely [MnTpCl](+) and [FeTpCl], due to in-state spin-orbit coupling. The anisotropy in these systems was shown to be very sensitive to perturbations, for example, chemical substitution and distortions due to the Jahn-Teller effect. We found that by substituting the hydrogen atoms in [MnTpCl](+) and [FeTpCl] by methyl and tert-butyl groups, certain covalent contributions to the magnetic anisotropy energy (MAE) could be controlled, thereby achieving higher values. Moreover, we showed that the selection of ion has important consequences for the symmetry of the ground spin-orbit term, opening the possibility of achieving zero magnetic tunneling even in non-Kramers ions. We have also shown that substitution may also contribute to a quenching of the Jahn-Teller effect, which could significantly reduce the magnetic anisotropy of the complexes studied.

Synthesis, characterization, DFT calculation and biological activity of square-planar Ni(II) complexes with tridentate PNO ligands and monodentate pseudohalides. Part II.

Three square-planar complexes of Ni(II) with condensation derivative of 2-(diphenylphosphino)benzaldehyde and 4-phenylsemicarbazide and monodentate pseudohalides have been synthesized and characterized on the basis of the results of X-ray, NMR and IR spectroscopy and elemental analysis. Investigated complexes exhibited moderate antibacterial and cytotoxic activity. The most pronounced cytotoxic activity (in the range of cisplatin) to HeLa cell line was observed for ligand and all the complexes. Azido complex and ligand induced concentration dependent cell cycle arrest in the S phase, as well as decrease of percentage of cells in G1 phase, without significant increase of apoptotic fraction of cells. The interaction of the azido complex and ligand with CT-DNA results in changes in UV-Vis spectra typical for non-covalent bonding. The observed intrinsic binding constant of azido complex-CT-DNA and ligand-CT-DNA were 3.22 × 10(5) M(-1) and 2.79 × 10(5) M(-1). The results of DNA cleavage experiments showed that azido complex nicked supercoiled plasmid DNA.

Lipophilicity assessment of ruthenium(II)-arene complexes by the means of reversed-phase thin-layer chromatography and DFT calculations.

The lipophilicity of ten ruthenium(II)-arene complexes was assessed by reversed-phase thin-layer chromatography (RP-TLC) on octadecyl silica stationary phase. The binary solvent systems composed of water and acetonitrile were used as mobile phase in order to determine chromatographic descriptors for lipophilicity estimation. Octanol-water partition coefficient, logK(OW), of tested complexes was experimentally determined using twenty-eight standard solutes which were analyzed under the same chromatographic conditions as target substances. In addition, ab initio density functional theory (DFT) computational approach was employed to calculate logK(OW) values from the differences in Gibbs' free solvation energies of the solute transfer from n-octanol to water. A good overall agreement between DFT calculated and experimentally determined logK(OW) values was established (R(2) = 0.8024-0.9658).

A Practical Computational Approach to Study Molecular Instability Using the Pseudo-Jahn-Teller Effect.

Vibronic coupling theory shows that the cause for spontaneous instability in systems presenting a nondegenerate ground state is the so-called pseudo-Jahn-Teller effect, and thus its study can be extremely helpful to understand the structure of many molecules. While this theory, based on the mixing of the ground and excited states with a distortion, has been long studied, there are two obscure points that we try to clarify in the present work. First, the operators involved in both the vibronic and nonvibronic parts of the force constant take only into account electron-nuclear and nuclear-nuclear interactions, apparently leaving electron-electron repulsions and the electron's kinetic energy out of the chemical picture. Second, a fully quantitative computational appraisal of this effect has been up to now problematic. Here, we present a reformulation of the pseudo-Jahn-Teller theory that explicitly shows the contributions of all operators in the molecular Hamiltonian and allows connecting the results obtained with this model to other chemical theories relating electron distribution and geometry. Moreover, we develop a practical approach based on Hartree-Fock and density functional theory that allows quantification of the pseudo-Jahn-Teller effect. We demonstrate the usefulness of our method studying the pyramidal distortion in ammonia and its absence in borane, revealing the strong importance of the kinetic energy of the electrons in the lowest a2″ orbital to trigger this instability. The present tool opens a window for exploring in detail the actual microscopic origin of structural instabilities in molecules and solids.

Substrate stereocontrol in the intramolecular organocatalyzed Tsuji-Trost reaction: enantioselective synthesis of allokainates.

Organocatalyzed Tsuji-Trost cyclization of 3b proceeds with asymmetric induction and allows for stereoselective synthesis of (+)-allokainic acid. The stereochemical outcome of the cyclization was predicted by calculations.