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Two isostructural complexes Ln(DOTAM)(H 2 O)(triflate) 3 ·3H 2 O (Ln = Eu, Nd) have been characterized by neutron diffraction analysis at different temperatures by means of two techniques, white-beam Laue at 65 K and monochromatic at 20 K, 65 K and 220 K. The high accuracy in the hydrogen-atom localization revealed the H-bonds network formed by the metal-coordinated water, the water molecules, the anions, and the macrocycle, as well as the non-symmetric orientation of the coordinated water with respect to the Ln-O w (w = water) axis. The accurate determination of Nd-H and Eu-H distances allows derivation of an averaged Gd-H value (2.974 A at 220 K) that is in the range of the smaller values commonly used in relaxivity calculations for Gd-based contrast agents.

The crystal structure of the complex (α R ,6 R )-Na[Gd(H 2 O)-AAZTA-C 2 H 4 COOBn]·3H 2 O·EtOH was determined by single crystal X-ray diffraction; the complex represents a bifunctional derivative of Gd-AAZTA, previously reported as original scaffold for the development of efficient contrast agents for MRI. The Gd(III) ion is nine coordinated with three nitrogens, five carboxylate oxygens and one water oxygen in a monocapped distorted square antiprism coordination polyhedron. Three of the five carboxylic groups are monodentate while a fourth is bidentate bridging an adjacent Gd ion with the formation of a polymeric structure. The influence on the overall structure of the propionate side arm introduced for conjugation purposes was discussed, and a computational approach to predict the structure of its (α R ,6 S ) isomer is presented and compared with the X-ray structure of the (α R ,6 R ) epimer.

New N-methyl and N-ethyl substitutions in the indazole nucleus are reported by reacting 3-(2-aminobenzamido)indazole and the appropriate trimethyl/triethyl orthobenzoate. Single crystal X-ray analysis confirms the N-ethylation position for the 3-(1-ethyl-1H-indazol-3-yl)-2-phenylquinazolin-4(3H)-one derivative 3f. Compounds 11a-d and 3a-d were tested to evaluate their antimicrobial, their antiproliferative activity and their COX inhibitory activities showing scarce or moderately antiproliferative activity and some inhibitory activity against COX-1 and COX-2.

The availability of drug affecting neuronal nicotinic acetylcholine receptors (nAChRs) may have important therapeutic potential for the treatment of several CNS pathologies. Pursuing our efforts on the systematic structural modification of cytisine and N-arylalkyl and N-aroylalkyl cytisines were synthesized and tested for the displacement of [(3)H]-epibatidine and [(125)I]-alpha-bungarotoxin from the most widespread brain nAChRs subtypes alpha(4)beta(2) and alpha(7), respectively. While the affinity for alpha(7) subtype was rather poor (K(i) from 0.4 to50 microM), the affinity for alpha(4)beta(2) subtype was very interesting, with nanomolar K(i) values for the best compounds. The N-substituted cytisines were docked into the rat and human alpha(4)beta(2) nAChR models based on the extracellular domain of a molluscan acetylcholine binding protein. The docking results agreed with the binding data, allowing the detection of discrete amino acid residues of the alpha and beta subunits essential for the ligand binding on rat and human nAChRs, providing a novel structural framework for the development of new alpha(4)beta(2) selective ligands.

Three cytisine derivatives, (-)-(7R,9S)-1-phenyl-3-(cytisin-12-yl)propan-1-one (1), (-)-(7R,9S)-1-phenyl-2-(cytisin-12-yl)ethane (2), and (-)-(7R,9S)-1,2-bis(cytisin-12-yl)ethane (3), with different electronic and steric features have been characterized by X-ray analysis and theoretical calculations in order to evaluate how structural modulations affect the intrinsic binding affinity at the neuronal nicotinic receptors (nAChRs). The crystal structures of 1 and 2, which display comparable affinities, are characterized by the same conformation of the cytisine moiety with different orientations of the substituent at N2. In 3, two independent molecules have the pyridinone rings diversely oriented. This compound has a lower affinity with respect to 1 and 2, but it increases the expression of neuronal nAChRs. Compounds 1, 2, and 3 retain the key prerequisite of the classical pharmacophoric models, with sp(3)-N-atom--HBA distances close to the expected value, both in solid state and in solution (theoretical calculations), where, in contrast with the extended in the crystal state, a curled-up conformation has been found, though maintaining the N-substituent in equatorial position.

The crystal structures of the ligand AAZTA (6-amino-6-methylperhydro-1,4-diazepine tetraacetic acid) and of its Gd complex Na[Gd(H 2 O)AAZTA] · 3H 2 O have been determined by single crystal X-ray diffraction. The AAZTA ligand crystallizes in a zwitterion form with two deprotonated carboxylic groups and two protonated tertiary nitrogen atoms. Two independent molecules of about a similar conformation and three water molecules as asymmetric units, are present in the crystal. In the solid state the gadolinium complex is a centrosymmetric dimer with a bicapped square antiprismatic coordination geometry around each metal ion. Two symmetric bridging carboxylate groups determine the dimer formation with Gd–O(2) and Gd–O(2)′ bond distances rather comparable of 2.526(4) and 2.548(4) A, respectively, while the Gd–O(1) (inner sphere water) bond distance is 2.443(5) A. A network of hydrogen bonds between the water of inner and outer spheres and the AAZTA carboxylic groups is present in the crystal structure.

The synthesis and characterization of new polynuclear lanthanide(III) ionic clusters of general formula [Ln 9 (acac) 16 (OH) 10 ] + [Mo 2 (CO) 10 (μ-H)]- (Ln = Sm, Eu, Gd, Dy, Yb) and [Sm 9 (acac) 16 OH) 10 ] + [CrW(CO) 10 (μ-H)] - is reported. The polynuclear complexes, prepared under pure nitrogen atmosphere by interaction of the hydridic metal carbonyls with the β-dichetonate Ln(acac) 3 ·3H 2 O (Ln=Sm, Eu, Gd, Dy, Yb). The new clusters were characterized by elemental analysis, complexometric titration for Ln, atomic absorption for Cr, W and Mo, gas-volumetric analysis for CO, FTIR spectroscopy and single crystal X-ray structure determination of [Sm 9 (acac) 16 (OH) 10 ][Mo 2 (CO) 10 (μ-H)]. The Eu and Yb complexes are isostructural to the Sm one for which, similarly to their homonuclear chromium and tungsten derivative analogues, a square antiprismatic arrangement of eight Sm ions with the ninth at the center of the antiprism has been found.

The two diastereomeric amino acid derivatives 8 (3a S ,5 R ,6a S )-5- tert -butoxycarbonylamino-4,5,6,6a-tetrahydro-3a H -cyclopenta[ d ]isoxazole-3,5-dicarboxylic acid diethyl ester, its epimer 9 (3a S ,5 S ,6a S ), and carboxylic acid 10 obtained by hydrolysis of 9 , which are intermediates in the synthesis of novel NMDA receptor antagonists 6 and 7 (Fig. 1), have been characterized by X-ray studies at 293 K for 8 and 10 , and at 100 K for 9 . The configuration of the carbon binding the 5- tert -butoxycarbonylamino moiety (BOC) determines the different molecular complexity: the chain structure for 8 , dimeric for 9 , and chain dimers for 10 . The pharmacophoric parameters in compound 8 (from which the active 7 is derived) are comparable with those observed for NMDA receptor antagonism, while 9 and 10 do not present the structural features, which match these pharmacophoric characteristics.

The diazonium salt derived from 4-amino-N,1,3-trimethyl-N-(3-methyl-1-phenyl-1H-pyrazol-5-yl)-1H-pyrazole-5-carboxamide (14) was reacted with a mixture of CuSO4 and NaCl, with ascorbic acid as an initiator to afford the planar derivative 4,6-dihydro-1,4,6,8-tetramethyl-3-phenyldipyrazolo[3,4-b:4′,3′-d]pyridin-5(3H)-one (16) and its unexpected isomer 4,6-dihydro-3,4,6,8-tetramethyl-1-phenyldipyrazolo[4,3-b:4′,3′-d]pyridin-5(1H)-one (17), as well as the epimers (3S,4S)- (or (3S,4R)-) and (3S,4R)- (or (3S,4S)-) 4-chloro-2,4-dihydro-1′,3′,5,5′-tetramethyl-2-phenylspiro[pyrazole-3,4′(1′H)-pyrrolo[3,4-c]pyrazol]-6′(5′H)-one (18a and b, respectively). Epimers 18a and b were converted under basic conditions to 4′-chloro-N,1,3,3′-tetramethyl-1′-phenyl-[4,5′-bi-1H-pyrazole]-5-carboxamide (19). The structures of isomers 16 and 17 determined by single-crystal X-ray analysis are also reported. Linear dichroism (LD) measurements for the above isomers suggest that 17 intercalates into DNA, and 17 exhibited antiproliferation activity against human NCI-H460 pulmonary carcinoma cells.

The crystal structures of the salts of (S)- and (R)-1,4-benzodioxane-2-carboxylic acid with (S)-1-phenylethylamine and its p-methyl and p-nitro substituted analogues were determined in order to correlate the differences in solubility between diastereomeric salts with their solid state structures. A common characteristic of the six structures is the presence of hydrogen bond interactions, which always involve the ammonium group NH3+ and the carboxylic oxygens of three adjacent acid molecules with the formation of molecular chains in the direction of the binary screw crystallographic axis (unique axis in the monoclinic system and, in the orthorhombic space group, coincident with the direction of the shortest cell axis). A determinant factor for the high inter diastereomer solubility difference of the two pairs of p-methyl and p-nitro substituted amine salts seems, in the case of the p-methyl derivatives, to be the different mutual disposition of the acid and amine aromatic rings at the boundaries of the molecular chains and, for the p-nitro derivatives, the prevalence, in the same region, of the nitro groups or of the acid aromatic moieties. A morphologic study at SEM revealed some correlation between the crystal habit and solubility. Theoretical calculations, based on the LSER model, account for the observed solubilities in methanol.

A 2.0 ns unrestrained Molecular Dynamics was used to elucidate the geometric and dynamic properties of the HSA binding sites. The structure is not stress affected and the rmsds calculated from the published crystallographic data are almost constant for all the simulation time, with an averaged value of 2.4A. The major variability is in the C-terminus region. The trajectory analysis of the IIA binding site put in evidence fast oscillations for the Cgamma@Leu203...Cgamma@Leu275 and Cgamma@Leu219...Cgamma@Leu260 distances, with fluctuations around 250 ps, 1000 ps and over for the first, while the second is smoothly increasing with the simulation time from 7 to 10A. These variations are consistent with a volume increase up to 20% confirmed by the inter-domain contacts analysis, in particular for the pair O@Pro148...Ogamma@Ser283, representing the change of distance between IB-h9 and IIA-h6, O@Glu149...Ogamma@Ser189 for sub-domains IB-h9/IIA-h1 and N@Val339...Odelta2@Asp447 sub-domains IIB-h9/IIIA-h1. These inter-domain motions confirm the flexibility of the unfatted HSA with possible binding site pre-formation.

The crystal structure of Acetylcholine Binding Protein (AChBP), homolog of the ligand binding domain of nAChR, has been used as model for computational investigations on the ligand-receptor interactions of derivatives of 6-chloropyridazine substituted at C3 with 3,8-diazabicyclo[3.2.1]octane, 2,5-diazabicyclo[2.2.1]heptane and with piperazine and homopiperazine, substituted or not at N4. The ligand-receptor complexes have been analyzed by docking techniques using the binding site of HEPES complexed with AChBP as template. The good relationship between the observed binding affinity and the calculated docking energy confirms that this model provides a good starting point for understanding the binding domain of neuronal nicotinic receptors. An analysis of the possible factors significant for the ligand recognition has evidenced, besides the cation-pi interaction, the distance between the chlorine atom of the pyridazinyl group and the carbonylic oxygen of Leu B112 as an important parameter in the modulation of the binding energy.

The reaction of 2-PySK with [Pt(dppf)Cl 2 ] [dppf=1,1 ′ -bis(diphenylphosfinoferrocene and 2-PyS=2-mercaptopyridine] produced Pt(dppf)(2-SPy) 2 ( 1 ) and its subsequent reaction with SnBu 2 (BF 4 ) 2 or SnBu 3 (BF 4 ) yielded [{Pt(dppf)(2-SPy)}{BF 4 }] ( 2 ). Compounds 1 and 2 were fully characterised by multinuclear NMR [ 1 H, 13 C{ 1 H}, 31 P{ 1 H} and 195 Pt{ 1 H}] and 57 Fe Mossbauer spectroscopies. In addition the structure of 2 was determined by X-ray crystallographic studies, which can be summarised as follows: monoclinic P 2 1 / c , a =9.9291(9) A, b =22.270(4) A, c =16.919(2) A, γ =103.6(9)°, V =3636.2(8) A 3 and Z =4. Finally, a thermal decomposition study was carried out with 2 in three different atmosphere: oxygen, nitrogen or hydrogen. The residues were characterised by X-ray powder diffraction (XRD), X-ray electron probe microanalysis (EPMA), scanning electron microscopy (SEM) and 57 Fe Mossbauer spectroscopy. The results have shown the formation of a disordered Pt 1 − x Fe x based alloy when the pyrolysis process was performed in H 2 , simultaneously with small amount of Fe(II) and Fe(III) phosphides. Furthermore, in oxygen and nitrogen the thermal decomposition of 2 produced metallic agglomerates of Pt dispersed in a combination of Fe(II) and Fe(III) phosphates in O 2 , and an intricate mixture of sulphides and phosphides in N 2 .

The reactions of iodoflavone with 3-methyl-3-hydroxybut-1-yne and 3-methylbut-3-en-2-yne are described and the antimicrobial and cytotoxic activities of the obtained compounds have been tested. The molecular structures of 6-(3-hydroxy-3-methylbut-1-ynyl)-flavone (1a) and 6-(3-methylbut-3-en-1-ynyl) flavone (1b) have been determined by X-ray crystallography. The planar configuration of the two compounds has been attributed to intramolecular hydrogen bond interactions. In 1a, the presence of the hydroxyl group determines a dimeric arrangement of the molecules. In both compounds in the crystal state, molecular stacking has been observed.

Four new estrone derivatives were isolated after treatment of estrone 3-methyl ether (3-methoxyestra-1,3,5(10)-trien-17-one (3) with tert-butyl hydroperoxide and cobalt acetate. Three of the four steroidal compounds − the 9α-(tert-butylperoxy)-6-one 4, the 9α-hydroxy-6-one 5, and the 9β-hydroxy-6-one 7 − originated from oxidation at the 6- and 9-positions. In contrast, oxidation of 3 to a 9β-(tert-butylperoxy) compound afforded the 8-hydroxy-9-cyclodecanone derivative 6 through a molecular rearrangement involving the cleavage of the 8−9 bond. The structures of the compounds were secured by spectroscopic evidence including COSY, HSQC, and NOESY experiments combined with X-ray crystallographic analysis and molecular modeling studies. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)

Lanthanide(III) complexes with composition Ln(nic)(H 2 O) n (pic) 3 (nic) (Ln=Pr, Nd n =8; Tm n =7) (pic=picrate, nic=nicotinamideN-O) were obtained by reaction of the hydrated lanthanide picrate with nicotinamideN-oxide in ethanol. They were characterized by elemental analysis and IR spectra. The molecular structures of Pr, Nd and Tm complexes were established by X-ray crystallography. Different triclinic phases have been detected for the isostructural Nd and Pr derivatives. They are nine coordinated to eight water molecules and a monodentate nic ligand while the apparently isomorphous Tm derivative looses a water molecule with a eight coordination number and a coordination geometry changing from tricapped trigonal prism (Pr, Nd) to square antiprismatic.

The lanthanide derivatives present important interactions with the biological system. In particular the peculiar stereochemical properties of the Ln 3+ complexes with DOTA and DOTA-substituted ligands, responsible for their thermodynamic stability and kinetic inertness, make them suitable for biomedical applications. Specifically, the Gd(DOTA) complexes, as they are among the most relevant contrast agents for MRI. The study of their interactions with HSA protein in particular, indicates the importance of the molecular shape of the complexes in addition to the suggested hydrophobic, van der Waals and electrostatic contributions.

3-[(3-Aminopropyl)amino]-1-oxo-1H-naphtho[2,1-b]pyran-2-carbaldehyde (10) was synthesized by nucleophilic substitution reaction of 2-(3-dimethylamino)-1-oxo-1H-naphtho[2,1-b]pyran-2-carbaldehyde (9) and the monoprotected propane-1,3-diamine. The reaction with the unprotected reagent led to the unexpected 1-(2-hydroxynaphthalen-1-yl)-2-(tetrahydropyrimidin-2(1H)-ylidene)ethanone (6). Extension of this reaction to chromone 16 gave 1-(2-hydroxy-3-isopropyl-6-methylphenyl)-2-(tetrahydropyrimidin-2(1H)-ylidene)ethanone (7). The X-ray crystal structures of 6 and 7 were also determined.

Lanthanide(III) complexes of six-nitrogen-donor macrocyclic ligands carrying a benzyl-type group, CH2C6H4X (X=H, OH, or NH2), at each di-imine side chain were synthesized by the metal-templated, cyclic Schiff-base condensation of 2,6-diacetylpyridine with substituted S- or R,S-1,2-diaminopropanes. The complexes were obtained as mixtures of constitutional isomers and stereoisomers, which were identified by 1H NMR spectra and separated by fractional crystallization. The molecular structure of the 11-coordinate complex [La(NO3)2(H2O)(C36H38N6)](NO3)(H2O) was established by X-ray crystallography.

The reactions of cis-[PtCl2(NCMe)2] with a fivefold excess of the primary aliphatic amines RNH2 (R=Me, Et, Pri, But) in CH2Cl2 at −10 °C afford in high yield the bis-amidine complexes cis-[PtCl2{ZN(H)C(NHR)Me}2], where both amidine ligands assume the Z configuration. The corresponding reactions of trans-[PtCl2(NCMe)2] with RNH2 (R=Me, Et, But) give a mixture of the bis-amidine trans-[PtCl2{ZN(H)C(NHR)Me}2] and the mono-amidine trans-[PtCl2(NCMe){ZN(H)C(NHR)Me}] derivatives, which could be isolated as pure products operating with a platinum nitrile complex:amine molar ratio of 1:50 or 1:1, respectively. The reaction of trans-[PtCl2(NCMe)2] with a 50-M excess of PriNH2 affords the bis-amidine bis-amine dicationic complex trans-[Pt(H2NPri)2{ZN(H)C(NHPri)Me}2]Cl2, which has been characterized also by X-ray diffraction analysis. The reactions of cis- and trans-[PtCl2(NCMe)2] with the secondary aliphatic amines R′R″NH yield the bis-amidine complexes cis- and trans-[PtCl2{EN(H)C(NR′R″)Me}2] (R′, R″=Et) and/or cis- and trans-[PtCl(NCMe){EN(H)C(NR′R″)Me}2] (R′, R″=Et; R′=Me, R″=But), where the amidine ligands have the E configuration. The compound trans-[PtCl2(NCMe){EN(H)C(NMeBut)Me}] has been characterized by single crystal X-ray diffraction. All the complexes have been characterized by IR, 1H and 13C NMR spectroscopies. The Z or E configuration of the amidine ligand can be readily deduced by 1H NMR data.

Complexes of Ca(II) and Sr(II) with six-nitrogen-donor macrocyclic ligands carrying a methyl group at each diimine side-chain were synthesized by the metal-templated condensation of 2,6-diacetylpyridine with R-, S-, or R,S-1,2-diaminopropane. The complexes exist as stereoisomers as well as constitutional isomers, which can be identified by 1H NMR spectra and separated by fractional crystallization. The molecular structure of the eight-coordinate complex [Sr(CF3SO3)2(C24H30N6)] was established by X-ray crystallography.

Synthesis and reactions of 6-chloro-7-fluoro-4-oxo-4H-chromene-3-carboxylic acid are described. The molecular structure of its achiral heterotopic 3-diethoxy-methyl precursor has been determined by NMR spectroscopy and X-ray crystallography. C14H14ClFO4 is monoclinic, space group P21/a, with unit cell dimensions a = 14.923(5), b = 6.615(2), c = 14.921(5) Å, β = 101.44(3)°, V = 1443.7(8) Å3, Z = 4, D calc. = 1.383 g/cm3.

X-ray diffraction analyses of 2-substituted cyclohexanone oximes C5H9(X)C=NOH [X = SMe (1), NMe2 (2)] and of the parent compound [X = H (3)] showed that their cyclohexyl rings are in a slightly distorted chair conformation. These compounds assume in the solid state the (E) configuration bearing the 2-substituents in the axial conformation. Compounds (1) and (2) exist as dimeric and polymeric hydrogen-bond associates, respectively. Low-temperature X-ray analysis of the cyclohexanone oxime (3) showed that the molecules are associated forming two independent trimers. The dimer in (1) and the trimer in (3) are built up via [O—H...N=C] hydrogen bonds, while the polymer of (2) is via the [OH...NMe2] hydrogen bond. The comparative IR νOH and νC=N analysis of the title compounds, in the solid state and in CCl4 solution, fully supports the nature of the associates for (1)–(3) obtained by X-ray diffraction. The IR azomethyne frequency shift analysis (ΔνC=N) also suggests the occurrence of the πC=N/σ*C—X orbital interaction which stabilizes the axial conformations of (1) and (2).

Lanthanide trifluoroacetate complexes (Ln=La, Pr, Nd, Sm, Tb, Gd, Tb, Er) with 2-azacyclononanone (AZA) were synthesized and characterized. Complexometric analysis with EDTA and microanalytical procedures agree with the general formula Ln(TFA) 3 · 3AZA; thermogravimetric curves in N 2 dynamic atmosphere show their thermal stability until about 100 °C. The europium emission spectrum indicates more than one Eu 3+ symmetry centre. The X-ray structure of the samarium complex consists of dimeric species where the metal atoms are connected through four TFA bridges, a monodentate TFA, two O-bonded AZA ligands and a water molecule complete the coordination sphere about each samarium.

The compounds [quinolinium]4[Bi2Cl10] (1), [isoquinolinium]4[Bi2Cl10].2H2O (2) and [8-hydroxyquinolinium]4[BiCl6]·Cl·2H2O (3) have been obtained by reacting bismuthate oxide and the appropriate base in HCl acid medium. The crystal structures of 1 and 2 consist of quinolinium and isoquinolinium cations, respectively, interacting through hydrogen bonding with [Bi2Cl10]4− dimers. The different degree of interactions in the two derivatives causes significant differences in the bond distances of the anions. The crystal structure of 3 is made of [BiCl6]3− and Cl− anions and 8-hydroxyquinolinium cations. Hydrogen bond interactions including the N-bonded and O-bonded H atoms together with an interstitial chlorine atom stabilize the entire crystal structure.

The reaction of cis-[PtCl2(NCMe)2] with a 5-fold excess of Me2NH in CH2Cl2 at −10°C affords in high yield the bis-amidine complex cis-[PtCl2{E-N(H)C(NMe2)Me}2] (E,E-2), where both the amidine ligands assume the E configuration. E,E-2 was characterized by X-ray structure analysis, NMR spectroscopy and electrospray ionization mass spectrometry (ESI-MS). The corresponding reactions of trans-[PtCl2(NCMe)2] with Me2NH gave the bis-amidine complex trans-[PtCl2{E-N(H)C(NMe2)Me}2] (E,E-3) and the mono-amidine derivative trans-[PtCl2{E-N(H)C(NMe2)Me}(NCMe)] (E-4).

The complexes trans-[FeH(NCR)(dppe)2][BF4] (1) (R=NH2, NMe2, NEt2 or NC(NH2)2; dppe=Ph2PCH2CH2PPh2) and trans-[FeL(NCR)(depe)2]Yn (R=NH2, NMe2, NEt2 or NC(NH2)2; depe=Et2PCH2CH2PEt2; Y=BF4 or BPh4; (2), L=Br, n=1; (3), L=NCR, n=2) have been prepared by treatment of trans-[FeHCl(dppe)2] (in THF and in the presence of Tl[BF4]) or trans-[FeBr2(depe)2] (in MeOH and in the presence of [NBu4][BF4] or Na[BPh4]), respectively, with the appropriate cyanamide. NMR and Mossbauer spectral, as well as FAB mass spectrometric data are reported. Mossbauer partial isomer shift (PIS) and partial quadrupole splitting (PQS) parameters have been estimated for the cyanamide and dppe ligands and rationalised, with the overall IS and QS, in terms of π- and σ-electronic effects, the cyanamides behaving as more effective σ-donors and weaker π-acceptors than organonitriles. FAB MS fragmentation patterns are also proposed. The crystal structures of 1 (R=NH2) and 3 (R=NEt2, Y=BF4) are reported.

The crystal and molecular structures of [(phenH)2Cl][Cr2(CO)10(μ-H)] (1) and [K(phen)2][Cr2(CO)10(μ-H)] (2) have been determined by single crystal X-ray diffraction. The availability of the potassium cation for the carbonyl oxygens coordination influences the conformation of the anion in 2 as demonstrated by the comparison with the non-coordinating [(phenH)2Cl] cation in 1 and with literature data.

The two isomorphous compounds [Ln2(pic)4(TDTD)3(H2O)2](pic)2(H2O)2 Ln = Tm, Lu; pic = picrate; TDTD = trans-1,4-dithiane-S,S′-dioxide) were synthesized and characterized by IR spectra and X-ray single-crystal structure analysis. The two independent metal cations have subtly different coordination spheres. One is eight coordinated with a square antiprismatic coordination geometry resulting from the bonding of two chelating picrate ligands, three oxygens of the TDTD ligands and water molecules. For the other the eight LnO(NO) contact is considerably longer, giving a seven coordinate endcapped trigonal prism. The sharing of the TDTD moieties among adjacent units results in the formation of polymeric structures in which uncoordinated picrate anions and water molecules are clathrated.

Pyrolysis of 4-aryl-5-amino-v-triazolines affords, generally, amidines and/or benzanilides. Pyrolysis of 4-aryl-5-morpholino-v-triazolines 6, together with the expected amidines 7 and/or aryanilides 8, produced the morpholinopyrroles 9. The reaction mechanism of this unusual transformation is discussed. Influence of solvent dipole moment in pyrrole formation is suggested. Pyrrole 9a [i.e. 2-(3-morpholin-4-yl-2,4-pyrrol-1-yl)-benzonitrile] has been fully characterized and its molecular structure has been determined by X-ray diffraction analysis.

3,3′-(1,2-ethanediyl)bis[2-substituted-1,3-thiazolidin-4-one] derivatives display different biological activities depending on the configuration of the 2,2′ centers and on the substitution at C2, C2′. In this context, 3,3′-(1,2-ethanediyl)bis[2-(2′-(5′-methyl)thienyl)-1,3-thiazolidin-4-one] (6b) and 3,3′-(1,2-ethanediyl)bis[2-(3′-pyridyl)-1,3-thiazolidin-4-one] (8b) have been prepared. Their structural and conformational features, which can be related to the biological activity, have been investigated by X-ray diffraction and molecular modeling techniques.

IR νCO and νSO frequencies of some α-sulfinylacetophenones [PhC(O)CH2S(O)R: R = Me 1, Et 2, Pri 3, Ph 4 and But 5] have been measured and their conformations are estimated with the help of ab initio 6-31G** calculations and X-ray diffraction analyses. The anomalous negative carbonyl frequency shifts for the cis2 rotamer together with the decrease of the cis∶gauche population ratio in solvents of increasing polarity for compounds 1–4 support the existence of a strong intramolecular interaction between CO and SO dipoles, which stabilizes the cis2 rotamer more than the πCO–σ*C–SO and π*CO–σC–SO orbital interactions stabilize the gauche3 rotamer. The stability of the cis2 rotamer is discussed in terms of the electrostatic attraction between the CO and SO dipoles along with the π*SO←nO(CO) charge transfer which lead to an O(CO)· · ·S(SO) contact shorter than the sum of the corresponding van der Waals radii. The gauche2 rotamer of 5 is more stable than the cis2 one in which steric strain between the carbonyl oxygen atom and the tert-butyl group is present.

The reaction between bismuthate oxide and phen (1,10-phenanthroline) in acid medium led to the isolation of the unusual [(PhenH)(PhenH2)][BiCl6]·2H2O derivative, which has been characterized by X-ray analysis and IR spectroscopy. The compound crystallizes in the triclinic space group \([\text[P\bar 1]]\) with a = 8.313(2), b = 9.349(2), c = 9.807(3) A, α = 86.39(3), β = 110.27(3) and γ = 106.48(3)°. The crystal structure is made of [BiCl6]3− anions and [(PhenH)(PhenH2)]3+ cations. A network of hydrogen bond interactions involving the two clathrated water molecules, the phenanthroline moiety and the chlorines characterizes the entire structure.

The diazonium salts obtained from 2-amino-N-methyl-N-(1-phenyl-3-methylpyrazol-5-yl)benzamide were reacted with cuprous oxide or copper at 5 or 25 °C under different pH conditions. Cuprous oxide at 25 °C and pH 6.25 yielded the racemic epimers (3′SR,4′RS)- and (3′SR,4′SR)-4′-hydroxy-2′,4′-dihydro-2,5′-dimethyl-2′-phenylspiro[isoindoline-1,3′-3′H-pyrazol]-3-ones 2 and 10 respectively, (RS)-2′,4′-dihydro-2,5′-dimethyl-2′-phenylspiro[isoindoline-1,3′-3′H-pyrazole]-3,4′-dione 9 and N-methylphthalimide 8. The thermal transformation of 2 and 10 into the potentially pharmacologically active 3-methyl-1-phenyl[2]benzopyrano[4,3-c]pyrazol-5(1H)-one 4 was strongly dependent on the structure of the two epimers. When 1 was reacted with cuprous oxide or copper sulfate and sodium halide (chloride or bromide), in the presence of ascorbic acid as initiator, a mixture of epimers (3′SR,4′RS)- and (3′SR,4′SR)-4′-chloro(or bromo)-2′,4′-dihydro-2,5′-dimethyl-2′-phenylspiro[isoindoline-1,3′-3′H-pyrazol]-3-ones 6b and 7b (or 6c and 7c) was obtained. The same epimers were obtained when the diazonium halides (chloride and bromide) 1b,c obtained from 2-amino-N-methyl-N-(1-phenyl-3-methyl-1H-pyrazol-5-yl)benzamide were treated with the appropriate classical Sandmeyer catalysts. The formation of the spiro compounds is based on consecutive Pschorr and Sandmeyer reactions. The X-ray crystal structures of the epimers 2 and 10 have been determined, confirming the given formulations.

The cyanoguanidine complex cis-[Pt(NCNC(NH2)2)2(PPh3)2][BPh4]2, prepared by reacting cis-[PtCl2(PPh3)2] with cyanoguanidine in the presence of Na[BPh4], readily reacts with methanol to give cis-[(PPh3)2PtNHC(OMe) = NC(NH2) = NH)] [BPh4] containing a novel type of azametallcycle whose molecuar structure is established by X-ray crystallography. Its formation involves metal-promoted nucleophilic addition of the alcohol to the cyano group of a cyanoguanidine ligand, combined with deprotonation of the guanidine unit which then chelates the Pt(II) centre.

This paper summarizes the results of recent studies on two important classes of lanthanide(III) complexes containing macrocyclic ligands. One class results from the ability of lanthanide(III) metal ions to promote the Schiff base condensation of appropriate diamine and dicarboxyl precursors, with the formation of unique macrocyclic ligands. The other class includes complexes obtained by reaction of the “free” lanthanide(III) ions with l,4,7,10-tetraazacyclododecane-N,N′,N″,N″′-tetraacetic acid (H4DOTA). The factors affecting the structural characteristic of these two classes of lanthanide macrocycles are discussed through a comparison of the relevant X-ray crystal structures.

The interaction of several β-diketones [pentane-2,4-dione, 1,3-diphenylpropane-1,3-dione, 1,1,1-trifluoro-4(2-thienyl)butane-2,4-dione] and their sodium salts with complexes of the type [ML(CH3COO)2]X·n(H2O), where M is LaIII, EuIII or YIII, L is the macrocyclic ligand C22H26N6, X is Cl− or CH3COO− and n is 4–9, was investigated in solution by NMR and luminescence spectroscopy. A number of crystalline ∗ML∗-(β-diketonate) complexes were isolated and characterized; the structure of one member of the series, [EuL(CH3COO)∗(C6H5CO)2CH∗](CH3COO) · 6(H2O), was established by X-ray crystallography. The structure is ionic; the 10-coordinate EuIII is bonded to the six nitrogens of the macrocyclic ligand, two oxygens of a bidentate acetate and two oxygens of the chelating β-diketonate. The coordinated acetate and the β-diketonate are situated on opposite sides of the ∗EuL∗ macrocycle; an uncoordinated acetate provides charge neutrality.

The syntheses of the ligand bis(benzylamide)diethylenetriaminepentaacetic acid (BBA-DTPA) and its Gd(III) and Lu(III) complexes are reported. The solid state structure of Lu(III) BBA-DTPA was determined in a single crystal X-ray diffraction study. The lutetium ion adopts a mine-coordinate geometry, which is best described as a distorted tricapped prism. Eight coordination sites are occupied by the ligand (three nitrogen atoms, two carboxamide oxygens and three carboxylate oxygens) and the ninth site is occupied by the oxygen atom of a water molecule. The VT 13 C NMR spectra of Lu(III) BBA-DTPA are consistent with the presence of three isomers in solution. Water proton relaxation rates have shown that Gd(III) BBA-DTPA displays an analogous behaviour to that observed for other Gd(III) complexes of related bisamide derivatives of DTPA. The solubility of Gd(III) BBA-DTPA has been markedly improved by the presence of an excess of hydroxypropyl-β-cyclodextrin. The thermodynamic stability of the inclusion complex has been evaluated by measuring the proton relaxation enhancement upon addition of β-cyclodextrin.

The cyclic five-membered platinum(II) oxycarbene complex trans-[Pt(Me){CCH(p-tolyl)CH2CH2O}(PPh3)2][BF4] (1) can be prepared in good yield under very mild conditions either by reaction of trans-[Pt(Me)(C⋮C-p-tolyl)(PPh3)2] with oxirane in the presence of 1 equiv of HBF4 or by reaction of the cationic solvato complex trans-[Pt(Me)(PPh3)2(solv)][BF4] with oxirane and 1.5 equiv of p-tolylacetylene. The X-ray crystal structure of 1 is reported.

White prismatic crystals of formula Sb(dpk.OCH 3 )(O 2 C 6 H 4 ) were synthesized from the reaction of Sb(O 2 C 6 H 4 )F and dpk in methanol solution. The complex has been characterized by X-ray crystallography and Mossbauer spectroscopy. The crystal structure is characterized by a previously unknown O⊃N coordinating mode of the dpk. OCH 3 ligand. The Sb ion coordination geometry is of the AX 4 Y 2 E type, with four primary bonds due to the chelation of the dpk. OCH 3 and of the catecholato ligands, while the two secondary contacts with the oxygens of a catecholate and two dpk. OCH 3 ligands of adjacent molecules determine the chain formation.

In the course of the reaction catalyzed by rhodanese, the enzyme cycles between two catalytic intermediates, the sulfur-free and the sulfur-substituted (persulfide-containing) forms. The crystal structure of sulfur-free rhodanese, which was prepared in solution and then crystallized, is highly similar to that of sulfur-substituted enzyme. The inactivation of sulfur-free rhodanese with a small molar excess of hydrogen peroxide relies essentially on a modification limited to the active site, consisting of the oxidation of the essential sulfhydryl to sulfenyl group (-S-OH). Upon reaction of the sulfur-free enzyme with monoiodoacetate in the crystal, the Cys-247 side chain with the bound carboxymethyl group is forced into a conformation that allows favorable interactions of the carboxylate with the four peptide NH groups that participate in hydrogen bonding interactions with the transferable sulfur atom of the persulfide group in the sulfur-substituted rhodanese. It is concluded that active site-specific chemical modifications of sulfur-free rhodanese do not lead to significant changes of the protein structure, consistent with a high degree of similarity of the structures of the sulfur-free and sulfur-substituted forms of the enzyme both in solution and in the crystal.

The TDCO thiocyanate complexes Eu(NCS)3 TDCO and Yb(NCS)3TDCO (TDCO = 1,7,10,16-tetraoxa-4,13-diazacyclooctadecane) have been synthesised and their X-ray structure determined. Both are monoclinic with 4 neutral molecules in the unit cell of dimensions a = 16.438(4), b = 15.211(3), c = 9.334(2) A , β = 90.37(3)°, V = 2333.8(9) A 3 , space group P2t/n for Eu and a = 17.481(3), b = 8.020(2), c = 18.056(3) A , β = 118.12(3)°, V = 2232.6(9) A 3 , space group P2t/c for Yb. They consist of nine-coordinated metal centres linked to six donor atoms of the macrocyclic ligand and to three monodentate isothiocyanate ligands situated on opposite sides of the macrocycle. The two structures present different conformations of the TDCO ligand. The mean bond lengths are EuO 2.56(2), YbO 2.498(9), EuN(ring) 2.60(1); YN(nng) 2.518(8) and EuN(CS) 2.44(1), YbN(CS) 2.365(9) A consistent with the difference in the Eu and Yb ionic radii.

The crystal and molecular structure of the [5S,15S] isomer of the [LaL(NCS)3] complex (L=C26H30N6) was determined by single crystal X-ray diffraction analysis. The compound crystallizes in the orthorhombic space group P212121 witha=13.647(4),b=19.504(4),c=11.606(4)A. The 9-coordinate La(III) is bound to the N atoms of three monodentate isothiocyanates and to the six N atoms of the macrocycle ligand L, which has an 18-membered, six-nitrogen donor cavity and two peripheral −CH3 substituents.

Summary A number of new 4-diazopyrazole derivatives were prepared by the reaction of 1- R -3-methyl-5(R 1 -substituted)benzamidopyrazoles with a sevenfold excess of nitrous acid in acetic medium. The compounds were tested for activity against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus faecalis, Listeria monocytogenes, Candida albicans, Candida tropicalis and Paecilomyces varioti . The highest microbial susceptibility was shown by Gram-positive bacteria, with minimum inhibitory concentrations (MIC) in the range 0.5–12.5 μg/mL. For S aureus the R 1 substituents were screened utilizing the Topliss operational scheme. The 4-nitro group was found to be the best substituent. We also tested the compounds 41,o,p , found to be the most active in the test against S aureus ATCC 25923, on ten clinical S aureus strains, five of which were sensitive and five resistant to methicillin. The above compounds were active in the range 2–8 μg/mL against methicillin-resistant S aureus strains. An X-ray analysis of compounds 4i and 4q is reported.

The chloro complexes trans-[Pt(Me)(Cl)(PPh3)2], after treatment with AgBF4, react with 1-alkynes HCCR in the presence of NEt3 to afford the corresponding acetylide derivatives trans-[Pt(Me) (CCR) (PPh3)2] (R = p-tolyl (1), Ph (2), C(CH3)3 (3)). These complexes, with the exception of the t-butylacetylide complex, react with the chloroalcohols HO(CH2)nCl (n = 2, 3) in the presence of 1 equiv. of HBF4 to afford the alkyl(chloroalkoxy)carbene complexes trans-[Pt(Me) {C[O(CH2)nCl](CH2R) } (PPh3)2][BF4] (R = p-tolyl, n = 2 (4), n = 3 (5); RPh, n = 2 (6)). A similar reaction of the bis(acetylide) complex trans-[Pt(CCPh)2(PMe2Ph)2] with 2 equiv. HBF4 and 3-chloro-1-propanol affords trans-[Pt(CCPh) {C(OCH2CH2CH2Cl)(CH2Ph) } (PMe2Ph)2][BF4] (7). T alkyl(chloroalkoxy)-carbene complex trans-[Pt(Me) {C(OCH2CH2Cl)(CH2Ph) } (PPh3)2][BF4] (8) is formed by reaction of trans-[Pt(Me)(Cl)(PPh3)2], after treatment with AgBF4 in HOCH2CH2Cl, with phenylacetylene in the presence of 1 equiv. of n-BuLi. The reaction of the dimer [Pt(Cl)(μ-Cl)(PMe2Ph)]2 with p-tolylacetylene and 3-chloro-1-propanol yields cis-[PtCl2{C(OCH2CH2CH2Cl)(CH2C6H4-p-Me}(PMe2Ph)] (9). The X-ray molecular structure of (8) has been determined. It crystallizes in the orthorhombic system, space group Pna21, with a = 11.785(2), b = 29.418(4), c = 15.409(3) A, V = 4889(1) A3 and Z = 4. The carbene ligand is perpendicular to the Pt(II) coordination plane; the PtC(carbene) bond distance is 2.01(1) A and the short C(carbene)-O bond distance of 1.30(1) A suggests extensive electronic delocalization within the PtC(carbene)O moietry.