Supramolecular synthons in hydrates and solvates of lamotrigine: a tool for cocrystal design.

The molecule of anti-epileptic drug lamotrigine [LAM; 3,5-diamino-6-(2,3-dichlorophenyl)-1,2,4-triazine] is capable of the formation of multicomponent solids. Such an enhanced tendency is related to the diverse functionalities of the LAM chemical groups able to form hydrogen bonds. Two robust synthons are recognized in the supramolecular structure of LAM itself formed via N-H...N hydrogen bond: homosynthon, so-called aminopyridine dimer or synthon 1 [R22(8)] and larger homosynthon 2 [R32(8)]. The synthetic procedures for a new hydrate and 11 solvates of LAM (in the series: with acetone, ethanol: two polymorphs: form I and form II, 2-propanol, n-butanol, tert-butanol, n-pentanol, benzonitrile, acetonitrile, DMSO and dioxane) were performed. The comparative solid state structural analysis of a new hydrate and 11 solvates of LAM has been undertaken in order to establish robustness of the supramolecular synthons 1 and 2 found in the crystal structure of LAM itself as well as LAM susceptibility to build methodical solid state supramolecular architecture in the given competitive surrounding of potential hydrogen bonds. The aminopyridine dimer homosynthon 1 [R22(8)] has been switched from para-para (P-P) topology to ortho-ortho (O-O) topology in all crystal structures, except in LAM:n-pentanol:water solvate where it remains P-P. Homosynthon 2 [R32(8)] of the LAM crystal structure imitates in the LAM solvates as a heterosynthon by replacing the triazine nitrogen proton acceptor atoms of LAM with the proton acceptors of solvates molecules.

Ligand-Modulated Nuclearity and Geometry in Nickel(II) Hydrazone Complexes: From Mononuclear Complexes to Acetato- and/or Phenoxido-Bridged Clusters.

The propensity of 4-hydroxybenzhydrazone-related ligands derived from 3-methoxysalicylaldehyde (H2L3OMe), 4-methoxysalicylaldehyde (H2L4OMe), and salicylaldehyde (H2LH) to act as chelating and/or bridging ligands in Ni(II) complexes was investigated. Three clusters of different nuclearities, [Ni3(L3OMe)2(OAc)2(MeOH)2]∙2MeOH∙MeCN (1∙2MeOH∙MeCN), [Ni2(HL4OMe)(L4OMe)(OAc)(MeOH)2]∙4.7MeOH (2∙4.7MeOH), and [Ni4(HLH)2(LH)2(OAc)2]∙4MeOH·0.63H2O·0.5MeCN·HOAc (3∙4MeOH·0.63H2O·0.5MeCN·HOAc), were prepared from Ni(OAc)2∙4H2O and the corresponding ligand in the presence of Et3N. The hydrazones in these acetato- and phenoxido-bridged clusters acted as singly or doubly deprotonated ligands. When pyridine was used, mononuclear complexes with the square-planar geometry seemed to be favoured, as found for complexes [Ni(L3OMe)(py)] (4), [Ni(L4Ome)(py)] (5) and [Ni(LH)(py)] (6). Ligand substituent effects and the stability of square-planar complexes were investigated and quantified by extensive quantum chemical analysis. Obtained results showed that standard Gibbs energies of binding were lower for square-planar than for octahedral complexes. Starting from [MoO2(L)(EtOH)] complexes as precursors and applying the metal-exchange procedure, the mononuclear complexes [Ni(HL3OMe)2]∙MeOH (7∙MeOH) and [Ni(HLH)]∙2MeOH (9∙2MeOH) and hybrid organic-inorganic compound [Ni2(HL4OMe)2(CH3OH)4][Mo4O10(OCH3)6] (10) were achieved. The octahedral complexes [Ni(HL)2] (7-9) can also be obtained by the direct synthesis from Ni(Oac)2∙4H2O and the appropriate ligand under specific reaction conditions. Crystal and molecular structures of 1∙2MeOH∙MeCN, 2∙4.7MeOH, 3∙4MeOH∙0.63H2O∙0.5MeCN∙HOAc, 4, 5, 9∙2MeOH, and 10 were determined by the single-crystal X-ray diffraction method.

Effective methods for the synthesis of hydrazones, quinazolines, and Schiff bases: reaction monitoring using a chemometric approach.

Synthesis of hydrazones (1a-4a and 1b-4b), quinazolines (3c·MeOH and 3d·MeOH), and hydrazone-Schiff bases (4c and 4d) is achieved by combining suitable aldehydes (2,3- or 2,4-dihydroxybenzaldehyde) with four hydrazides (isonicotinic, nicotinic, and 2- or 4-aminobenzoic acid hydrazide). A suite of approaches for their preparation is described: solution-based synthesis, mechanosynthesis, and solid-state melt reactions. The mechanochemical approach is generally a better choice for the quinazolines, while the solid-state melt reaction is more efficient for derivatives of (iso)nicotinic based hydrazones. Crystalline amine-functionalised hydrazones 4a and 4b undergo post-synthetic modifications in reactions with 3- or 4-pyridinecarbaldehyde vapours to form hydrazone-Schiff bases 4a-3py, 4b-3py, 4a-4py, and 4b-4py. Mechanochemical and vapour-mediated reactions are followed by ex situ powder X-ray diffraction and IR-ATR methods, respectively. The chemometric analysis of these data using principal component analysis provided an insight into the reaction profiles and reaction times. Azines (5a and 5b), achieved from aldehydes and hydrazine, reversibly change colour in response to temperature changes. The structures of all products are ascertained by a combined use of spectroscopic and X-ray diffraction methods. The cytotoxic and antimicrobial activities of all compounds against selected human cancer cell lines and bacterial strains are evaluated.

Assessment of Haemostasis in patients undergoing emergent neurosurgery by rotational Elastometry and standard coagulation tests: a prospective observational study.

BACKGROUND: Rotational elastometry (ROTEM) has been shown useful to monitor coagulation in trauma patients and in major elective surgery. In this study, we aimed to evaluate the utility of ROTEM to identify hemostatic disturbances and to predict the need for transfusion, compared with standard coagulation tests (SCTs) in patients undergoing emergent neurosurgery. METHODS: Over a four-year period, adult patients who met criteria for emergent neurosurgery lasting more than 90 min were included in the study. Blood was collected preoperatively and analyzed with SCTs (international normalized ratio [INR], fibrinogen concentration, prothrombin time [PT or Quick], partial thromboplastine time [PTT], fibrinogen concentration and platelet count), and ROTEM assays. Correlations between SCTs and ROTEM parameters as well as receiver operating characteristic curves were performed to detect a coagulopathic pattern based on standard criteria and the need for transfusing at least 3 units of packed red blood cells (PRBCs). RESULTS: In a cohort of 92 patients, 39 (42%) required ≥3 PRBCs and a coagulopathic pattern was identified in 32 patients based on SCTs and in 19 based on ROTEM. There was a strong correlation between PTT and INTEM coagulation time (R = 0.76) as well as between fibrinogen concentrations and FIBTEM maximal clot firmess (R = 0.70). The need for transfusion (≥ 3 PRBCs) was best predicted by the maximal clot firmess of EXTEM and FIBTEM (AUC of 0.72 and 0.71, respectively) and by fibrinogen concentration (AUC of 0.70). CONCLUSIONS: In patients undergoing emergent neurosurgery, ROTEM analysis provides valid markers of early coagulopathy and predictors of blood transfusion requirements.

A tetra-nuclear cubane-like nickel(II) complex with a tridentate salicyl-idene-imine Schiff base ligand: tetra-kis-[µ3-4-methyl-N-(2-oxidophen-yl)salicylideneiminato]tetra-kis-[methano-lnickel(II)] methanol 0.8-solvate.

The tetra-nuclear title complex, [Ni4(C14H11NO2)4(CH3OH)4]·0.8CH3OH, has a distorted cubane topology shaped by four Schiff base ligands. The cubane [Ni4(µ3-O4)] core is formed via the O atoms from the Schiff base ligands. The octa-hedrally coordinated NiII ions occupy alternating vertices of the cube. Each NiII ion is coordinated by one O,N,O'-tridentate dianionic ligand, two O atoms of oxidophenyl groups from adjacent ligands and the O atom of a coordinating methanol mol-ecule. The cubane core is stabilized via an intra-molecular O-H⋯O hydrogen bond between the hy-droxy group of the coordinating methanol mol-ecules and the phenolate O atom of the aldehyde Schiff base fragment. Additional stabilization is obtained via intra-molecular C-H⋯O hydrogen bonds involving aromatic C-H groups and the oxygen atoms of adjacent methanol mol-ecules. In the crystal, complex mol-ecules are linked into chains parallel to the c axis via weak C-H⋯O hydrogen bonds. The partial-occupancy disordered methanol solvent mol-ecule has a site occupancy of 0.8 and is linked to the tetra-nuclear unit via an inter-molecular C-H⋯O hydrogen bond involving a phenolate O atom.

Impact of early haemodynamic goal-directed therapy in patients undergoing emergency surgery: an open prospective, randomised trial.

Haemodynamic goal-directed therapies (GDT) may improve outcome following elective major surgery. So far, few data exist regarding haemodynamic optimization during emergency surgery. In this randomized, controlled trial, 50 surgical patients with hypovolemic or septic conditions were enrolled and we compared two algorithms of GDTs based either on conventional parameters and pressure pulse variation (control group) or on cardiac index, global end-diastolic volume index and stroke volume variation as derived from the PiCCO monitoring system (optimized group). Postoperative outcome was estimated by a composite index including major complications and by the Sequential Organ Failure Assessment (SOFA) Score within the first 3 days after surgery (POD1, POD2 and POD3). Data from 43 patients were analyzed (control group, N = 23; optimized group, N = 20). Similar amounts of fluid were given in the two groups. Intraoperatively, dobutamine was given in 45 % optimized patients but in no control patients. Major complications occurred more frequently in the optimized group [19 (95 %) versus 10 (40 %) in the control group, P < 0.001]. Likewise, SOFA scores were higher in the optimized group on POD1 (10.2 ± 2.5 versus 6.6 ± 2.2 in the control group, P = 0.001), POD2 (8.4 ± 2.6 vs 5.0 ± 2.4 in the control group, P = 0.002) and POD 3 (5.2 ± 3.6 and 2.2 ± 1.3 in the control group, P = 0.01). There was no significant difference in hospital mortality (13 % in the control group and 25 % in the optimized group). Haemodynamic optimization based on volumetric and flow PiCCO-derived parameters was associated with a less favorable postoperative outcome compared with a conventional GDT protocol during emergency surgery.

Erythromycin for Gastric Emptying in Patients Undergoing General Anesthesia for Emergency Surgery: A Randomized Clinical Trial.

IMPORTANCE: Patients undergoing emergency procedures under general anesthesia have impaired gastric emptying and are at high risk for aspiration of gastric contents. Erythromycin has strong gastric prokinetic properties. OBJECTIVE: To evaluate the efficacy of erythromycin lactobionate in gastric emptying in patients undergoing emergency surgery. DESIGN, SETTING, AND PARTICIPANTS: The Erythro-Emerge trial was a single-center, randomized, double-blinded, placebo-controlled clinical trial in patients undergoing emergency surgery under general anesthesia at Geneva University Hospitals. We included 132 patients from March 25, 2009, through April 10, 2013, and all patients completed the study. Randomization was stratified for trauma and nontrauma procedures. The randomization code was opened on April 23, 2013, and analyses were performed through July 26, 2013. We performed an intention-to-treat analysis. INTERVENTIONS: Patients were randomized to intravenous erythromycin lactobionate, 3 mg/kg, or placebo 15 minutes before tracheal intubation. Patients were followed up for 24 hours. MAIN OUTCOMES AND MEASURES: The primary outcome was a clear stomach, defined as less than 40 mL of liquids and no solids and identified through endoscopy immediately after intubation. The secondary outcome was the pH level of residual gastric content. RESULTS: A clear stomach was diagnosed in 42 of 66 patients (64%) receiving placebo compared with 53 of 66 patients (80%) receiving erythromycin (risk ratio, 1.26 [95% CI, 1.01-1.57]). In the population undergoing surgery for nontrauma, the association between receipt of erythromycin and having a clear stomach (adjusted odds ratio [95% CI]) was statistically significant (13.4 [1.49-120]; P = .02); in the population undergoing surgery for trauma, it was not (1.81 [0.64-5.16]; P = .26). Median (interquartile range) pH of the residual gastric liquid was 2 (1-4) in 36 patients receiving placebo and 6 (3-7) in 16 receiving erythromycin (P = .002). Patients receiving erythromycin had nausea (20 [30%] vs 4 [6%]) and stomach cramps (15 [23%] vs 2 [3%]) more often than those receiving placebo. One patient receiving erythromycin vomited before induction of anesthesia. CONCLUSIONS AND RELEVANCE: In patients undergoing general anesthesia for emergency procedures, erythromycin administration increased the proportion with a clear stomach and decreased the acidity of residual gastric liquid. Erythromycin was particularly efficacious in the nontrauma population. Adverse effects were minor. Further large-scale studies are warranted to confirm the potential of erythromycin to reduce the incidence of bronchoaspiration in patients undergoing emergency surgery. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00827216.

Goal-directed hemostatic therapy using the rotational thromboelastometry in patients requiring emergent cardiovascular surgery.

AIMS AND OBJECTIVES: We assessed the clinical impact of goal-directed coagulation management based on rotational thromboelastometry (ROTEM) in patients undergoing emergent cardiovascular surgical procedures. MATERIALS AND METHODS: Over a 2-year period, data from 71 patients were collected prospectively and blood samples were obtained for coagulation testing. Administration of packed red blood cells (PRBC) and hemostatic products were guided by an algorithm using ROTEM-derived information and hemoglobin level. Based on the amount of PRBC transfused, two groups were considered: High bleeders (≥5 PRBC; HB) and low bleeders (<5 PRBC; LB). Data were analyzed using Chi-square test, unpaired t-test and analysis of variance as appropriate. RESULTS: Pre-operatively, the HB group (n = 31) was characterized by lower blood fibrinogen and decreased clot amplitude at ROTEM compared with the LB group (n = 40). Intraoperatively, larger amounts of fibrinogen, fresh frozen plasma and platelets were required to normalize the coagulation parameters in the HB group. Post-operatively, the incidence of major thromboembolic and ischemic events did not differ between the two groups (<10%) and the observed in-hospital mortality was significantly less than expected by the Physiological and Operative Severity Score for the enumeration of Mortality and Morbidity (POSSUM score, 22% vs. 35% in HB and 5% vs. 13% in LB group). CONCLUSIONS: ROTEM-derived information is helpful to detect early coagulation abnormalities and to monitor the response to hemostatic therapy. Early goal-directed management of coagulopathy may improve outcome after cardiovascular surgery.

[Treatment of septic shock by removing blood endotoxin]. / Traitement du choc septique par epuration extracorporelle de l'endotoxine circulante.

Sepsis and its complications remain the principal cause of death in intensive care units, and is associated with high costs. Protocolized care of septic shock has however lately been associated with decreased death rates, but to date there is still no specific treatment for sepsis. Pharmacologic therapies aiming at blocking the action of bacterial endotoxin or its receptor have been largely disappointing. Epuration of circulating endotoxin using hemoadsorption on polymyxin columns is a new treatment in septic shock showing encouraging preliminary results. Studies reporting such results, and hypotheses for a potential beneficial effect of this type of therapy are discussed in this article.

Antiproliferative potency of novel benzofuran-2-carboxamides on tumour cell lines: cell death mechanisms and determination of crystal structure.

In this manuscript the synthesis and biological activity of novel heterocyclic derivatives of benzofuran-2-carboxamides 3a-j and 6a-f is presented. Biological evaluation in vitro revealed that only few compounds exerted concentration-depended antiproliferative effects on tumour cell lines at micromolar concentrations. In particular, 2-imidazolynyl substituted compound 6f showed selectivity on SK-BR-3 cell line while 2-N-acetamidopyridyl substituted 3h and 2-imidazolynyl substituted amide 3i showed selective concentration-dependent antiproliferative effects on SW620 cell line. Compounds 3h and 6f induced apoptosis while compound 3i acted through a cell death mechanism other than apoptosis.

Benzimidazole derivatives related to 2,3-acrylonitriles, benzimidazo[1,2-a]quinolines and fluorenes: synthesis, antitumor evaluation in vitro and crystal structure determination.

A synthesis and biological evaluation of new benzimidazole derivatives, related to 2,3-disubstituted acrylonitriles, benzimidazo[1,2-a]quinoline-6-carbonitriles and heteroaromatic fluorenes was described. The molecular and crystal structures of three compounds 4, 16 and 17 reveal that non-fused fluoro derivative, 4, deviates from planarity by 13.11(2) degrees, while fused methyl, 16, and fluoro, 17, derivatives are planar within 4 degrees exhibiting a planar aromatic surface capable to intercalate into double-stranded DNA. Compound 4 exists as E-isomer. The crystal structures confirmed that hydrogen bonding patterns are characterized dominantly by the weak C-H...N(F) bonds, except in the case of 4 where the presence of ethanol molecule of crystallization resulted in the N-H...O and O-H...N hydrogen bonds formation. In the crystal structures of 16 and 17 cyano group participates in hydrogen bonding formation, while in 4 this is not the case. All compounds, except 16 and 14 exerted pronounced antiproliferative activity on five tumor cell lines, whereby 2-benzimidazolyl-3-N-methylpyrolyl-acrylonitrile 13 and its fused analogue 23 exerted the highest activity on all cell lines (IC50=0.8-30 microM) and showed a special selectivity toward HeLa cells. There is no major difference in the biological activity between non-fused and fused analogues. Similarly, all compounds showed significant interaction with ct-DNA, supporting the fact that their antitumor activity could partially be the consequence of DNA-binding. The cyano moiety is important for the activity, but not the selectivity of tested compounds.

Novel cyano- and amidinobenzothiazole derivatives: synthesis, antitumor evaluation, and X-ray and quantitative structure-activity relationship (QSAR) analysis.

Synthesis of a series of novel cyano- and amidinobenzothiazole derivatives 3-31 is described. All studied amidino derivatives showed noticeable antiproliferative effect on several tumor cell lines. Cyano derivatives 11-17 showed considerably less pronounced activity because of their poor solubility in aqueous cell culture medium, which was confirmed by the principal components (PC) analysis. Compounds 21, 22, 28, and 29 were tested for their effects on the cell cycle and apoptosis, whereby 22 and 29, having methyl group at the C-6 position in pyridine ring, showed drastic cell cycle perturbations that were both concentration- and time-dependent and induced apoptosis. The QSAR modeling, based on the physicochemical descriptors and on the measured biological activities, indicated the relevance of molecular polarizability and particular distribution of pharmacophores on the molecular surface for activity. In conclusion, benzothiazoles containing either isopropylamidino or imidazolyl groups will be considered as starting compounds for further investigation on lead identification.

S-2-Amino-5-(dimethyl-ammonio)phenyl sulfothio-ate.

The title compound, C(8)H(12)N(2)O(3)S(2), has been isolated as an inter-mediate in the synthesis of methyl-ene blue dye, the best known phenothia-zine dye, and structurally characterized as a zwitterion. The crystal structure is dominated by inter-molecular N-H⋯O hydrogen bonds between the amine and sulfothio-ate groups, with graph-set motif C(9)R(2) (2)(8), involving anti-parallel chains and a centrosymmetric eight-membered ring. A hydrogen bond with graph-set motif R(2) (2)(14) between the ammonium and sulfothio-ate groups completes the two-dimensional network in the ab plane. Inter-molecular C-H⋯O hydrogen bonds are also present in the crystal.

S-5-Amino-2-(dimethyl-ammonio)phenyl sulfothio-ate.

The title compound, C(8)H(12)N(2)O(3)S(2), has been isolated as a by-product in the synthesis of methyl-ene blue dye. The compound crystallizes with four independent mol-ecules in the unit cell (Z'= 4). The zwitterionic form of the mol-ecule was established on the basis of the hydrogen atom located at the dimethyl-amino group. The crystal structure is dominated by inter-molecular hydrogen bonds of the N-H⋯O type formed between amino and ammonio N-H groups and O atoms from the sulfothio-ate group. There are in addition two weak inter-molecular N-H⋯N inter-actions and some non-conventional C-H⋯O hydrogen bonds.

A new coordination mode of 6-methylnicotinic acid in trans-tetraaquabis(6-methylpyridine-3-carboxylato-kappaO)cobalt(II) tetrahydrate.

The title compound, [Co(C7H6NO2)2(H2O)4] x 4 H2O, contains a Co(II) ion lying on a crystallographic inversion centre. The Co(II) ion is octahedrally coordinated by two 6-methylpyridine-3-carboxylate ligands in axial positions [Co-O = 2.0621 (9) A] and by four water molecules in the equatorial plane [Co-O = 2.1169 (9) and 2.1223 (11) A]. There are also four uncoordinated water molecules. The 6-methylpyridine-3-carboxylate ligands are bound to the Co(II) ion in a monodentate manner through a carboxylate O atom. There is one strong intramolecular O-H...O hydrogen bond, and six strong intermolecular hydrogen bonds of type O-H...O and one of type O-H...N in the packing, resulting in a complex three-dimensional supramolecular structure.

A one-dimensional CdII coordination polymer: catena-poly[cadmium(II)-bis(mu-6-methylpicolinato)].

In the title compound, [Cd(C(7)H(6)NO(2))2]n, the Cd(II) ion has a distorted octahedral geometry. The 6-methylpyridine-2-carboxylate anions are perpendicular to one another and act as bidentate and bridging ligands. Two carboxylate O atoms bridge the Cd(II) ions, forming centrosymmetric dinuclear units. These units are further connected via carboxylate O atoms into a one-dimensional polymeric chain which extends in the [100] direction.

trans-Bis(dimethyl sulfoxide-kappaO)bis(3-oxo-3,4-dihydroquinoxaline-2-carboxylato-kappa2N1,O2)copper(II).

The title compound, [Cu(C(9)H(5)N(2)O(3))(2)(C(2)H(6)OS)(2)], consists of octahedrally coordinated Cu(II) ions, with the 3-oxo-3,4-dihydroquinoxaline-2-carboxylate ligands acting in a bidentate manner [Cu-O = 1.9116 (14) A and Cu-N = 2.1191 (16) A] and a dimethyl sulfoxide (DMSO) molecule coordinated axially via the O atom [Cu-O = 2.336 (5) and 2.418 (7) A for the major and minor disorder components, respectively]. The whole DMSO molecule exhibits positional disorder [0.62 (1):0.38 (1)]. The octahedron around the Cu(II) atom, which lies on an inversion centre, is elongated in the axial direction, exhibiting a Jahn-Teller effect. The ligand exhibits tautomerization by H-atom transfer from the hydroxyl group at position 3 to the N atom at position 4 of the quinoxaline ring of the ligand. The complex molecules are linked through an intermolecular N-H...O hydrogen bond [N...O = 2.838 (2) A] formed between the quinoxaline NH group and a carboxylate O atom, and by a weak intermolecular C-H...O hydrogen bond [3.392 (11) A] formed between a carboxylate O atom and a methyl C atom of the DMSO ligand. There is a weak intramolecular C-H...O hydrogen bond [3.065 (3) A] formed between a benzene CH group and a carboxylate O atom.

Methyl 4-(1'-carboxyferrocen-1-yl)butyrate.

The title compound, [Fe(C6H5O2)(C10H13O2)], contains a heteroannularly substituted ferrocene unit, with the two substituents, viz. 3-(methoxycarbonyl)propyl and carboxyl, both capable of forming O-H...O hydrogen bonds. The keto ester group is stereochemically hindered by the trimethylene spacer and does not participate in intramolecular hydrogen-bond formation. Instead, the carboxy groups form self-complementary intermolecular hydrogen bonds [O...O = 2.650 (2) A], which join the molecules into centrosymmetric dimers with a graph-set descriptor R(2)2(8).

Iodo(picolinato-kappa(2)N,O)(picolinic acid-kappa(2)N,O)mercury(II).

The title compound, [Hg(C(6)H(4)NO(2))I(C(6)H(5)NO(2))], has twofold symmetry along the Hg-I bond. The Hg(II) ion coordinates one I atom [at 2.6045 (4) Angstrom], two N and two O atoms [at 2.298 (3) and 2.481 (2) Angstrom] from one picolinate ion, and one picolinic acid molecule in a very irregular trigonal-bipyramidal coordination. The single hydroxy H atom required for chemical neutrality is both statistically (by crystal symmetry) and structurally disordered, and is involved in an intermolecular O-H...O hydrogen bond [O...O = 2.455 (4) Angstrom], connecting the molecules into one-dimensional infinite chains along the [101] direction.

Chemical and radiological profile of the coal ash landfill in Kastel Gomilica.

The objective of this study was to determine the chemical, radiological and leaching properties of slag and ash produced by a thermoelectric unit of a former factory Adriavinil and deposited in the area of Kasktel Gomilica near Split, Croatia. A total of 33 samples were analysed. The bioavailable fraction of the slag and ash was estimated using different leaching tests. The waste material was characterized by a high activity of naturally occurring radionuclides 238U, 235U and 226Ra and by elevated concentrations of heavy metals. The concentrations of most heavy metals were three to four times as high as in the common soil. Uranium slag and ash concentration was almost 40 times higher than in control soil. More than 37% of the total U could be removed from the slag and ash with the sea water.