Stereoselective Asymmetric Syntheses of Molecules with a 4,5-Dihydro-1H-[1,2,4]-Triazoline Core Possessing an Acetylated Carbohydrate Appendage: Crystal Structure, Spectroscopy, and Pharmacology.

A new series of chiral 4,5-dihydro-1H-[1,2,4]-triazoline molecules, featuring a ß-ᴅ-glucopyranoside appendage, were synthesized via a 1,3-dipolar cycloaddition reaction between various hydrazonyl chlorides and carbohydrate Schiff bases. The isolated enantiopure triazolines (8a-j) were identified through high-resolution mass spectrometry (HRMS) and vibrational spectroscopy. Subsequently, their solution structures were elucidated through NMR spectroscopic techniques. Single-crystal X-ray analysis of derivative 8b provided definitive evidence for the 3-D structure of this compound and revealed important intermolecular forces in the crystal lattice. Moreover, it confirmed the (S)-configuration at the newly generated stereo-center. Selected target compounds were investigated for anti-tumor activity in 60 cancer cell lines, with derivative 8c showing the highest potency, particularly against leukemia. Additionally, substituent-dependent anti-fungal and anti-bacterial behavior was observed.

Ternary Phenolate-Based Thiosemicarbazone Complexes of Copper(II): Magnetostructural Properties, Spectroscopic Features and Marked Selective Antiproliferative Activity against Cancer Cells.

The new diprotic ligand 3,5-di-tert-butylsalicylaldehyde 4-ethyl-3-thiosemicarbazone, abbreviated H2(3,5-t-Bu2)-sal4eT, exists as the thio-keto tautomer and adopts the E-configuration with respect to the imine double bond, as evidenced by single-crystal X-ray analysis and corroborated by spectroscopic characterisation. Upon treatment with Cu(OAc)2·H2O in the presence of either 2,9-dimethyl-1,10-phenanthroline (2,9-Me2-phen) or 1,10-phenanthroline (phen) as a co-ligand in MeOH, this thiosemicarbazone undergoes conformational transformation (relative donor-atom orientations: syn,anti → syn,syn) concomitantly with tautomerisation and double deprotonation to afford the ternary copper(II) complexes [Cu{(3,5-t-Bu2)-sal4eT}(2,9-Me2-phen)] (1) and [Cu2{3,5-t-Bu2)-sal4eT}2(phen)] (2). Crystallographic elucidation has revealed that complex 1 is a centrosymmetric dimer of mononuclear copper(II) complex molecules brought about by intermolecular H-bonding. The coordination geometry at the copper(II) centre is best described as distorted square pyramidal in accordance with the trigonality index (τ = 0.14). The co-ligand adopts an axial-equatorial coordination mode; hence, there is a disparity between its two Cu-N coordinate bonds arising from weakening of the apical one as a consequence of the tetragonal distortion. The axial X-band ESR spectrum of complex 1 is consistent with retention of this structure in solution. Complex 2 is a centrosymmetric dimer of dinuclear copper(II) complex molecules exhibiting intermolecular H-bonding and π-π-stacking interactions. The two copper(II) centres, which are 4.8067(18) Å apart and bridged by the thio-enolate nitrogen of the quadridentate thiosemicarbazonate ligand, display two different coordination geometries, one distorted square planar (τ4 = 0.082) and the other distorted square pyramidal (τ5 = 0.33). Such dinuclear copper(II) thiosemicarbazone complexes, which are crystallographically characterised, are extremely rare. In vitro, complexes 1 and 2 outperform cisplatin as antiproliferative agents in terms of potency and selectivity towards HeLa and MCF-7 cancer cell lines.

Unusual Magneto-Structural Features of the Halo-Substituted Materials [FeIII (5-X-salMeen)2 ]Y: a Cooperative [HS-HS]↔[HS-LS] Spin Transition.

X-ray structures of the halo-substituted complexes [FeIII (5-X-salMeen)2 ]ClO4 (X=F, Cl, Br, I) [salMeen=N-methyl-N-(2-aminoethyl)salicylaldiminate]at RT have revealed the presence of two discrete HS complex cations in the crystallographic asymmetric unit with two perchlorate counter ions linking them by N-Hamine ⋅⋅⋅Operchlorate interactions. At 90 K, the two complex cations are distinctly HS and LS, a rare crystallographic observation of this coexistence in the FeIII -salRen (R=alkyl) spin-crossover (SCO) system. At both temperatures, crystal packing shows dimerization through C-Himine ⋅⋅⋅Ophenolate interactions, a key feature for SCO cooperativity. Moreover, there are noncovalent contacts between the complex cations through type-II halogen-halogen bonds, which are novel in this system. The magnetic profiles and Mössbauer spectra concur with the structural analyses and reveal 50 % SCO of the type [HS-HS]↔[HS-LS] with a broad plateau. In contrast, [FeIII (5-Cl-salMeen)2 ]BPh4 ⋅2MeOH is LS and exhibits a temperature-dependent crystallographic phase transition, exemplifying the influence of lattice solvents and counter ions on SCO.

Tuning a single ligand system to stabilize multiple spin states of manganese: a first example of a hydrazone-based manganese(III) spin-crossover complex.

A series of bis-chelate pseudo-octahedral mononuclear coordination complexes of manganese with the chromophore [MnN4 O2 ](n+) (n=0, 1) have been generated in all three principal oxidation states of this transition-metal center under ambient conditions by utilizing a readily tunable, versatile phenolic pyridylhydrazone ligand system (i.e., H2 (3,5-R(1) ,R(2) )-L; L=ligand). Strategic combinations of the nature and position of a variety of substituent groups afforded selective, spontaneous stabilization of multiple spin states of the manganese center, which, upon close crystallographic scrutiny, appears to be in part due to the occurrence or absence of hydrogen-bonding interactions that involve the phenolate/phenolic oxygen atom. The divalent complexes are isolable in two forms, namely, molecular [Mn(II) {H(3,5-R(1) ,R(2) )-L}2 ] and ionic [Mn(II) {H2 (3,5-R(1) ,R(2) )-L}{H(3,5-R(1) ,R(2) )-L}]ClO4 , with the latter complex converting easily into the former complex on deprotonation. Accessibility of the higher-valent states is achievable only when the phenolate oxygen atom is sterically hindered from participation in hydrogen bonding. The [Mn(III) {H(3,5-tBu2 )-L}2 ]ClO4 complex is the first example of a hydrazone-based Mn(III) complex to exhibit spin crossover. Formation of the tetravalent complexes [Mn(IV) {(3,5-R(1) ,R(2) )-L}2 ] (R(1) =tBu, R(2) =H; R(1) =R(2) =tBu) necessitates base-assisted abstraction of the hydrazinic proton.

Accessibility and selective stabilization of the principal spin states of iron by pyridyl versus phenolic ketimines: modulation of the 6A1 ↔ 2T2 ground-state transformation of the [FeN4O2]+ chromophore.

Several potentially tridentate pyridyl and phenolic Schiff bases (apRen and HhapRen, respectively) were derived from the condensation reactions of 2-acetylpyridine (ap) and 2'-hydroxyacetophenone (Hhap), respectively, with N-R-ethylenediamine (RNHCH(2)CH(2)NH(2), Ren; R = H, Me or Et) and complexed in situ with iron(II) or iron(III), as dictated by the nature of the ligand donor set, to generate the six-coordinate iron compounds [Fe(II)(apRen)(2)]X(2) (R = H, Me; X(-) = ClO(4)(-), BPh(4)(-), PF(6)(-)) and [Fe(III)(hapRen)(2)]X (R = Me, Et; X(-) = ClO(4)(-), BPh(4)(-)). Single-crystal X-ray analyses of [Fe(II)(apRen)(2)](ClO(4))(2) (R = H, Me) revealed a pseudo-octahedral geometry about the ferrous ion with the Fe(II)-N bond distances (1.896-2.041 Å) pointing to the (1)A(1) (d(π)(6)) ground state; the existence of this spin state was corroborated by magnetic susceptibility measurements and Mössbauer spectroscopy. In contrast, the X-ray structure of the phenolate complex [Fe(III)(hapMen)(2)]ClO(4), determined at 100 K, demonstrated stabilization of the ferric state; the compression of the coordinate bonds at the metal center is in accord with the (2)T(2) (d(π)(5)) ground state. Magnetic susceptibility measurements along with EPR and Mössbauer spectroscopic techniques have shown that the iron(III) complexes are spin-crossover (SCO) materials. The spin transition within the [Fe(III)N(4)O(2)](+) chromophore was modulated with alkyl substituents to afford two-step and one-step (6)A(1) ↔ (2)T(2) transformations in [Fe(III)(hapMen)(2)]ClO(4) and [Fe(III)(hapEen)(2)]ClO(4), respectively. Previously, none of the X-salRen- and X-sal(2)trien-based ferric spin-crossover compounds exhibited a stepwise transition. The optical spectra of the LS iron(II) and SCO iron(III) complexes display intense d(π) → p(π)* and p(π) → d(π) CT visible absorptions, respectively, which account for the spectacular color differences. All the complexes are redox-active; as expected, the one-electron oxidative process in the divalent compounds occurs at higher redox potentials than does the reverse process in the trivalent compounds. The cyclic voltammograms of the latter compounds reveal irreversible electrochemical generation of the phenoxyl radical. Finally, the H(2)salen-type quadridentate ketimine H(2)hapen complexed with an equivalent amount of iron(III) to afford the µ-oxo-monobridged dinuclear complex [{Fe(III)(hapen)}(2)(µ-O)] exhibiting a distorted square-pyramidal geometry at the metal centers and considerable antiferromagnetic coupling of spins (J ≈ -99 cm(-1)).

Coordination versatility of tridentate pyridyl aroylhydrazones towards iron: tracking down the elusive aroylhydrazono-based ferric spin-crossover molecular materials.

The two potentially tridentate and monoprotic Schiff bases acetylpyridine benzoylhydrazone (HL(1)) and acetylpyridine 4-tert-butylbenzoylhydrazone (HL(2)) demonstrate remarkable coordination versatility towards iron on account of their propensity to undergo tautomeric transformations as imposed by the metal centre. Each of the pyridyl aroylhydrazone ligands complexes with the ferrous or ferric ion under strictly controlled reaction conditions to afford three six-coordinate mononuclear compounds [Fe(II)(HL)(2)](ClO(4))(2), [Fe(II)L(2)] and [Fe(III)L(2)]ClO(4) (HL = HL(1) or HL(2)) displaying distinct colours congruent with their intense CT visible absorptions. The synthetic manoeuvres rely crucially on the stoichiometry of the reactants, the basicities of the reaction mixtures and the choice of solvent. Electrochemically, each of these iron compounds exhibits a reversible metal-centred redox process. By all appearances, [Fe(III)(L(1))(2)]ClO(4) is one of only two examples of a crystallographically elucidated iron(III) bis-chelate compound of a pyridyl aroylhydrazone. Several pertinent physical measurements have established that each of the Schiff bases stabilises multiple spin states of iron; the enolate form of these ligands exhibits greater field strength than does the corresponding neutral keto tautomer. To the best of our knowledge, [Fe(III)(L(1))(2)]ClO(4) and [Fe(III)(L(2))(2)]ClO(4) are the first examples of ferric spin crossovers of aroylhydrazones. Whereas in the former the spin crossover (SCO) is an intricate gradual process, in the latter the (6)A(1)↔(2)T(2) transition curve is sigmoidal with T(½)∼280 K and the SCO is virtually complete. As regards [Fe(III)(L(1))(2)]ClO(4), Mössbauer and EPR spectroscopic techniques have revealed remarkable dependence of the spin transition on sample type and extent of solvation. In frozen MeOH solution at liquid nitrogen temperature, both iron(III) compounds exist wholly in the doublet ground state.

Spectrofluorimetric determination of aluminium using 2-hydroxy-1-naphthylidene-(8-aminoquinoline).

A sensitive and selective spectrofluorimetric method has been developed for the rapid determination of aluminium. This method is based on the complex formation between aluminium and 2-hydroxy-1-naphthylidene-(8-aminoquinoline) (HNAQ). The optimum conditions for the complex formation were a metal-to-ligand (M : L) stoichiometric ratio of 1:1, a pH of 5.5 and a 0.20 m acetate buffer. The fluorescence of the complex was monitored at an emission wavelength of 502 nm with excitation at 438 nm. Under these conditions, linear calibration curves were obtained in the ranges 0.05-1 and 1-5 ppm. The detection limit was 3.4 ppb for the former and 13.5 ppb for the latter. The maximum relative standard deviation of the method for an aluminium standard of 200 ppb was 1.5% (n = 5). This method was successfully applied for the determination of aluminium in drinking water, pharmaceutical antacid tablets and suspension samples.

Thermally induced two-step, two-site incomplete 6A1<-->2T2 crossover in a mononuclear iron(III) phenolate-pyridyl Schiff-base complex: a rare crystallographic observation of the coexistence of pure S=5/2 and 1/2 metal centers in the asymmetric unit.

The six-coordinate mononuclear iron(III) complexes [Fe(salpm)2]ClO(4).0.5EtOH, [Fe(salpm)2]Cl, [Fe{(3,5-tBu2)-salpm}2]X (X=ClO4- or Cl-), and [Fe{(3,5-tBu2)-salpm}2]NO(3).2H2O [Hsalpm=N-(pyridin-2-ylmethyl)salicylideneamine; H(3,5-tBu2)-salpm=N-(pyridin-2-ylmethyl)-3,5-di-tert-butylsalicylideneamine] have been synthesized and isolated in crystalline form; their chemical identities have been ascertained by elemental analyses, FAB mass spectrometry, and infrared spectroscopy. The room-temperature effective magnetic moments [(8chiMT)1/2 approximately 5.85-5.90 microB] of these complexes are consistent with the high-spin (S=5/2) ground state. These complexes are intensely colored on account of the strong ppi-->dpi* LMCT visible absorptions. Definitive evidence for the structures of [Fe(salpm)2]ClO(4).0.5EtOH and [Fe{(3,5-tBu2)-salpm}2]NO(3).2H2O has been provided by single-crystal X-ray crystallography. The monomeric complex cations in both compounds comprise two uninegative phenolate-pyridyl tridentate Schiff-base ligands coordinated meridionally to the iron(III) to afford a distorted octahedral geometry with a trans,cis,cis-[FeO2N4] core. Whereas [Fe(salpm)2]ClO(4).0.5EtOH undergoes a thermally induced 6A1<-->2T2 crossover, [Fe{(3,5-tBu2)-salpm}2]NO(3).2H2O retains its spin state in the solid state down to 5 K. However, EPR spectroscopy reveals that the latter complex does exhibit a spin transformation in solution, albeit to a much lesser extent than does the former. The spin crossover in [Fe(salpm)2]ClO(4).0.5EtOH has resulted in an unprecedented crystallographic observation of the coexistence of high-spin and low-spin iron(III) complex cations in equal proportions around 100 K. At room temperature, the two crystallographically distinct ferric centers are both high spin; however, one [Fe(salpm)2]+ complex cation undergoes a complete spin transition over the temperature range approximately 200-100 K, whereas the other converts very nearly completely between 100 and 65 K; approximately 10% of the complex cations in [Fe(salpm)2]ClO(4).0.5EtOH remain in the high-spin state down to 5 K.

Iron(III) complexes with a biologically relevant aroylhydrazone: crystallographic evidence for coordination versatility.

Complexation of iron(III) with the heterodonor chelating agent 3,5-di-tert-butylsalicylidene benzoylhydrazine, H2(3,5-tBu2)salbh, in the absence or presence of a base affords the complex cation [Fe{H(3,5-tBu2)salbh}2]+ or the neutral compound [Fe{H(3,5-tBu2)salbh}{(3,5-tBu2)salbh}], respectively, as revealed by single-crystal X-ray analyses. Such a synthetic and crystallographic demonstration of the coordination versatility of an aroylhydrazone toward iron is uncommon. The oxidation and spin states of the iron have been verified with magnetic and spectroscopic measurements.

Unprecedented [V2O]6+ core of a centrosymmetric thiosemicarbazonato dimer: spontaneous deoxygenation of oxovanadium(IV).

The complex cation [{V(daptsc)(MeOH)}2(mu-O)]2+ [daptsc(2-) = 2,6-diacetylpyridine bis(thiosemicarbazonate)] is the first crystallographically elucidated dimer to possess a [V2O]6+ core, the [V(IV)-O-V(IV)]6+ structural unit, formed by cleavage of the multiple bond in the oxo-cation VO2+, is linear with the oxo group residing on a crystallographic center of inversion, and the temperature dependence of the magnetic data of the dimer is consistent with weak antiferromagnetic coupling of the d1-d1 centers.

Bis[(2-pyridyl)(2-pyridylamino)methanolato]cobalt(III) perchlorate: a consequence of cobalt ion-assisted oxidative deamination of a tris(pyridyl)aminal ligand.

The title compound, [Co(C11H10N3O)2]ClO4, designated [Co(L2)2]ClO4, was synthesized by reaction of Co(II) with two molar equivalents of (2-pyridyl)bis(2-pyridylamino)methane (L1) under ambient conditions, whereby the divalent metal ion was oxidized concomitantly with oxygenation and deamination of the aminal polydentate ligand to generate the tridentate ligand anion (2-pyridyl)(2-pyridylamino)methanolate, L2-. In the X-ray crystal structure of the complex cation, [Co(L2)2]+, the two L2- ligands are coordinated to the central cobalt(III) metal ion in a facial mode to afford a pseudo-octahedral geometry. The four pyridyl N atoms constitute the equatorial plane on which the cobalt(III) ion lies; the methanolate O atoms occupy the axial positions.

A phenolate-induced trans influence: crystallographic evidence for unusual asymmetric coordination of an alpha-diimine in ternary complexes of iron(III) possessing biologically relevant hetero-donor N-centered tripodal ligands.

Three mononuclear ternary complexes of iron(III) with an alpha-diimine (bipy or phen) and a derivative of N,N-bis(2-hydroxybenzyl)glycinate (L3-) have been synthesized and characterized by magnetic susceptibility measurements, electron paramagnetic resonance (EPR) spectroscopy, vibrational spectroscopy, and electronic absorption spectroscopy. Single-crystal X-ray structure determinations of the pseudo-octahedral complexes [Fe(bipy)L] x MeCN [L = (3,5-Br2)-L3- or (5,3-Cl,Me)-L3-] revealed a considerable and consistent distortion in the coordination of bipy to iron(III) attributable largely to electronic effects. In both crystal structures, the Fe-N(pyridyl) bond trans to the phenolate oxygen is 0.133 A longer than the other one positioned trans to the tertiary amine nitrogen, a relatively weaker donor. This coordination behavior of bipy is of structural interest and has not been observed previously for iron(III). The electronic and EPR spectra of the compounds [Fe(L'-L')L] x MeCN (L'-L' = bipy or phen) are consistent with the spin state of the central metal atom (S = 5/2). The charge-transfer transitions arising from the strong interactions of the phenolate moieties with the ferric ion have been identified as phenolate (p(pi)) --> iron(III) (d(pi*)) (lambda(max) approximately 500 nm, epsilon approximately 3000 M(-1) cm(-1)) and phenolate (p(pi)) --> iron(III) (d(sigma*) (lambda(max) approximately 320 nm, epsilon approximately 5200 M(-1) cm(-1)). The presence of the phenolate moieties in the quadridentate hetero-donor tripodal ligands, H3L, lends these iron(III) ternary complexes the potential to model the specific metal-coordination, metal-substrate interactions, and physicochemical behaviors of several iron-tyrosinate proteins.

Synergistic anion-directed coordination of ferric and cupric ions to bovine serum transferrin--an inorganic perspective.

A series of new iron(III) and copper(II) complexes of bovine serum transferrin (BTf), with carbonate and/or oxalate as the synergistic anion, are presented. The complexes [Fe(2)(CO(3))(2)BTf], [Fe(2)(C(2)O(4))(2)BTf], [Cu(2)(CO(3))(2)BTf] and [Cu(C(2)O(4))BTf] were prepared by standard titrimetric techniques. The oxalate derivatives were also obtained from the corresponding carbonate complexes by anion-displacement. The site-preference of the transition metal-oxalate synergism has facilitated the preparation and isolation of the mononuclear complex [Cu(C(2)O(4))BTf], the mixed-anion complexes [Cu(2)(CO(3))(C(2)O(4))BTf] and [Fe(2)(CO(3))(C(2)O(4))BTf] and the mixed-metal complex [FeCu(C(2)O(4))(2)BTf]. The sensitivity of electron paramagnetic resonance (EPR) spectroscopy to the nature of the synergistic anions at the specific-binding sites of the transferrins has made this physical technique particularly indispensable to this study. None of the other members of the transferrin family of proteins has ever been demonstrated to bind the ferric and cupric ions one after the other, each occupying a separate specific-binding site of the same transferrin molecule, as a response to the coordination restrictions imposed by the oxalate ion. The bathochromic shift of the visible p(pi)-d(pi*) CT band for iron(III)-BTf and the hypsochromic shift of the p(pi)-d(sigma*) CT band for copper(II)-BTf, on replacing carbonate by oxalate as the associated anion, are consistent with the relative positions of these anionic ligands in the spectrochemical series and the nature of the d-type acceptor orbitals involved in the CT transitions. The binding and spectroscopic properties of bovine serum transferrin--a serum transferrin--very nearly mirror those of human serum transferrin, but differ significantly from those of human lactoferrin.