Pyrene-based dyad and triad leading to a reversible chemical and redox optical and magnetic switch.

Two new pyrene-polychlorotriphenylmethyl (PTM) dyads and triads have been synthesized and characterized by optical, magnetic, and electrochemical methods. The interplay between the different electronic states of the PTM moiety in the dyads and triads and the optical and magnetic properties of the molecules have been studied. The electronic spectra of the radicals 5(.) and 6(.) show the intramolecular charge-transfer transition at around 700 nm due to the acceptor character of the PTM radical. In the diamagnetic protonated derivatives 3 and 4 the fluorescence due to the pyrene is maintained, whereas in the radicals 5(.) and 6(.) and the corresponding anions 5(-) and 6(-) there is a clear quenching of the fluorescence, which is more efficient in the case of radicals. The redox activity of PTM radicals that are easily reduced to the corresponding carbanion has been exploited to fabricate electrochemical switches with optical and magnetic response.

Tris(triazole) tripodal receptors as selective probes for citrate anion recognition and multichannel transition and heavy metal cation sensing.

The three-armed pyrenyl-triazole receptor 1 behaves as a highly selective fluorescent molecular sensor for citrate anions over similar carboxylates such as malate or tartrate. In addition, this receptor senses Cu(2+) cations through absorption and emission channels even in the presence of Hg(2+) metal cations. The related three-armed ferrocenyl-triazole receptor 2 behaves as a highly selective dual (redox and chromogenic) chemosensor molecule for Pb(2+) metal cations.

A novel N,P,C cage complex formed by rearrangement of a tricyclic phosphirane complex: on the importance of non-covalent interactions.

The reaction of Li/Cl P-CPh3 phosphinidenoid tungsten(0) complex 2 with dimethylcyanamide afforded tricyclic phosphirane complex 4, an unprecedented rearrangement of which led to the novel N,P,C cage complex 6. On the basis of DFT calculations, formation and intramolecular [3+2] cycloaddition of the transient nitrilium phosphane ylide complex 3 to a phenyl ring of the triphenylmethyl substituent to give 4 is proposed. Furthermore, theoretical evidence for terminal N-amidinophosphinidene complex 7, formed by [2+1] cycloelimination from 4, is provided, and the role of the electronic structure and non-covalent interactions of intermediate 7 discussed.

Oxaphosphirane-borane complexes: ring strain and migratory insertion/ring-opening reactions.

DFT-based HSAB-related parameters predict most favorable P- versus O-complexation of parent oxaphosphirane (1) with a variety of borane reagents BR3 (2). In general, strong P-B bonds are formed, especially for R: H (3a), Cl (3d), and C6F5 (3g), in agreement with large dissociation energies, whereas O-B bonds are usually weaker. A remarkable increase in ring strain is observed upon P-complexation of phosphirane or oxaphosphiranes, especially in the case of 3g and 3d, whereas a moderate decrease occurs in the case of O-complexation for both oxirane and oxaphosphiranes. Stronger P-B bonds also correlate with larger charge transfer from the oxaphosphirane to the borane units. This in turn increases electron density at the boron center and weakens all B-R bonds, thus enabling migratory insertion/ring-opening reactions in which a substituent from the borate center shifts to a ring atom; these reactions are additionally driven by release of the high ring strain of P-complexes 3.

Nitrogen-rich multinuclear ferrocenophanes as multichannel chemosensor molecules for transition and heavy-metal cations.

[m.n] Multinuclear ferrocenophanes prepared by aza-Wittig reaction of bisiminophosphoranes derived from 1,1'-diazidoferrocene and isophthaladelhyde or 2,5-diformylthiophene, behave as efficient electrochemical and chromogenic chemosensor molecules for Zn2+, Pb2+, and Hg2+ metal cations. Whereas the OSWV of receptor 3, bearing two m-phenylene units in the bridges, display one oxidation peak, receptor 4 incorporating two thiophene rings in the bridges, exhibits two well-separated oxidation peaks. In both receptors only the addition of Zn2+, Pb2+, and Hg2+ metal cations induced a remarkable anodic shift of ferrocene/ferrocenium redox couple. Likewise, in the absorption spectra of these receptors the low energy band is red-shifted by Δλ = 165 - 209 nm, and these changes promoted a significant color changes which could be used for the naked eye detection of these metal cations. The coordination modes for two representative cases were unveiled by DFT calculations that show an unsual coordination in the [42Pb]2+ complex with the Pb2+ cation in a distorted cubic N4S4 donor cage.

Bis(carbazolyl)ureas as selective receptors for the recognition of hydrogenpyrophosphate in aqueous media.

Recognition properties of the novel bis(carbazole) tris-ureidic-based receptors 1 and 2 toward different anions have been studied by (1)H NMR and absorption and emission spectroscopy, as well as by DFT calculations. Receptor 1, in which the two urea-functionalized arms are decorated with p-nitrophenyl rings, behaves as a highly selective chromogenic molecular probe for hydrogenpyrophosphate anion in a competitive medium (acetonitrile/water, 70/30). Receptor 2, bearing two urea arms decorated with photoactive pyrenyl rings, acts as a highly selective fluorescent molecular probe for hydrogenpyrophosphate anion in either acetonitrile or an aqueous mixture (acetonitrile/water, 85/15). Receptor 2 exhibits a dual monomer-excimer emission spectrum and undergoes a remarked ratiometry in acetonitrile in the presence of hydrogenpyrophosphate: the excimer band disappears, whereas the monomer band is slightly increased. However, in the aqueous mixture, a strong increase of the excimer emission band was observed, while the monomer emission bands remained almost unaffected. The resulting binding modes and spectroscopic features are explained by suitable structures of model complexes for both receptors. In such complexes, a peripheral cooperative effect was found, alleviating the excess of negative charge in the guest toward the outer surface of the host, as well as the required enlargement on its internal cavity.

Exocyclic bond cleavage in oxaphosphirane complexes?

A first computational insight into the intrinsic strength of exocyclic bonds to phosphorus in oxaphosphirane κP-pentacarbonylmetal(0) complexes 1a-f (M=Cr, Mo) is provided using a set of P-R derivatives (R=Me, tBu, CPh(3)). Whereas homolytic cleavage of the exocyclic P-R bond was found to be always unfavored (for neutral complexes), heterolytic cleavage leading to a carbocation R(+) moiety and the oxaphosphiranide complex 2(-) constitutes the lowest-energy process, especially if R is bulky and can stabilize the positive charge, that is, triphenylmethyl (trityl), efficiently. The energies required for P-M bond cleavage are about 30 kcal mol(-1), and decrease with the increasing bulk of the R substituent (from Me to trityl) and ongoing from Cr to Mo. The reactivities of complexes 1a-f towards oxidative and reductive single electron transfer (SET) reactions were analyzed using the facile variation of bond-strength-related descriptors (VBSD) methodology, thus enabling the design of synthetically useful strategies addressing decomplexation and P-functionalization. Reductive SET reactions with sodium naphthalenides enable selective P-M bond cleavage (i.e., decomplexation) for the case of P-Me and P-tBu substitution, whereas reductive P-R bond cleavage is favored in the case of the P-trityl complexes 1c,f, and results in the formation of the (anionic) oxaphosphiranide complex 2(-), which may be regarded as a potential key intermediate for further P-functionalization.

Ion pair recognition receptor based on an unsymmetrically 1,1'-disubstituted ferrocene-triazole derivative.

The ferrocene-triazole derivative 4, available from 1,1'-bis(diazido)ferrocene by sequential functionalization through click-type chemistry and the Staudinger reaction, is elaborated as a lab-on-a-molecule for the selective sensing of HP(2)O(7)(3-) and Hg(2+). Receptor 4 behaves as a ratiometric fluorescent probe for HP(2)O(7)(3-) with a good selectivity over other anions, whereas in the presence of Hg(2+) it modifies the fluorescent emission of the pyrene unit, acting as a selective on-off fluorescent sensor for Hg(2+) with a low detection limit. The most salient feature of compound 4 is its behavior as an excellent electrooptical ion pair recognition receptor able to simultaneously recognize Pb(2+) cations in the presence of HP(2)O(7)(3-) anion through multichannel perturbations of the redox potential of the ferrocene unit, the emission spectrum, and a noticeable color change from yellow to green.

Synthesis and reactions of the first room temperature stable Li/Cl phosphinidenoid complex.

P-Trityl substituted Li/Cl phosphinidenoid tungsten(0) complex (OC)5W{Ph3CP(Li/12-crown-4)Cl} (3) was prepared via chlorine/lithium exchange in complex (OC)5W{Ph3CPCl2} (2) using (t)BuLi in the presence of 12-crown-4 in tetrahydrofuran (THF) at low temperature; complex 3 possesses significantly increased thermal stability in contrast to previously reported analogue derivatives. Terminal phosphinidene-like reactivity of 3 was used in reactions with benzaldehyde and isopropyl alcohol as oxaphosphirane complex (OC)5W{Ph3CPC(Ph)O} (5) and phosphinite complex (OC)5W{Ph3CP(H)O(i)Pr} (6) were obtained selectively. Reaction of 3 with phosgene allowed to obtain the first kinetically stabilized chloroformylphosphane complex (OC)5W{Ph3CP(Cl)C(O)Cl} (4). Density functional theory (DFT) calculations revealed remarkable differences in the degree of P-Li bond dissociation 3a-d: using a continuum model 3 displays a covalent character of P-Li bond (COSMO (THF)) (a), which becomes elongated if 12-crown-4 is coordinated to lithium (b) and is cleaved if a dimethylether unit is additionally coordinated to lithium (c). A similar result was obtained for the case of 3(thf)4 in which also a solvent-separated ion pair structure is present (d). All products were unambiguously characterized by various spectroscopic means and, in the case of 2 and 4-6, by single-crystal X-ray diffraction analysis. In all structures very long P-C bonds were determined being in the range from 1.896 to 1.955 Å.

Single electron transfer-mediated selective endo- and exocyclic bond cleavage processes in azaphosphiridine chromium(0) complexes: a computational study.

Azaphosphiridines κP pentacarbonylchromium(0) complexes 2a,b (2a: R = H; 2b: R = Me) exhibit an average ring strain ranging from 24.2 to 25.7 kcal mol(-1) as obtained from homodesmotic reactions at the LPNO-NCEPA1/def2-TZVPP//BP86/def2-TZVP level. Parent azaphosphiridine chromium complex 1 is more stable than the ylidic P-iminiumphosphanide chromium complex isomer 6, which is obtained from (formal) endocyclic P-C bond cleavage. Computational evidence is provided for an insertion of carbon monoxide into the P-N bond of 1 to form 1,3-azaphosphetidin-2-one chromium complex 11, as the reaction was exergonic by -15.1 kcal mol(-1). The VBSD (variation of bond strength descriptors) methodology unveiled that SET (single electron transfer) oxidation of trimethyl-azaphosphiridine chromium complex 2b results in selective endocyclic P-C bond cleavage to afford the trimethyl-iminiumphosphanyl radical cation complex 13(•+). SET reduction of a wide variety of differently P-substituted azaphosphiridine complex derivatives (2a: R = H; 2b: R = Me; 2c: R = Cp; 2d: R = Cp*; 2e: R = CHTms(2); 2f: R = CMe(3); 2g: R = CMe(2)Ph; 2h: R = CMePh(2); 2j: R = Ph; 2k: R = C(6)F(5); Cp*: pentamethylcyclopentadienyl; Tms: trimethylsilyl) lead to selective decomplexation and thus to the corresponding unligated azaphosphiridines 14. Only in case of the P-trityl substituted azaphosphiridine complexes 2i does the SET reduction preferably cleave the exocyclic P-C bond thus affording azaphosphiridinide complex 12(-) and the triphenylmethyl radical.

Computational studies on azaphosphiridines, or how to effect ring-opening processes through selective bond activation.

The relative energies of azaphosphiridine and its isomers, the ring stability towards valence isomerization, and the ring strain, as well as the kinetics and thermodynamics of possible ring-opening reactions of P(III) derivatives (1-5) and P(V) chalcogenides (6-9; O to Te), were studied at high levels of theory (up to CCSD(T)). The barrier to inversion at the nitrogen atom in the trimethyl-substituted P(III) derivative 5 increases from 12.11 to 15.25 kcal mol(-1) in the P-oxide derivative 6 (P(V)); the relatively high barrier to inversion at the phosphorus in 5 (75.38 kcal mol(-1)) points to a configurationally stable center (MP2/def2-TZVPP//BP86/def2-TZVP). The ring strain for azaphosphiridine 5 (av. 22.6 kcal mol(-1)) was found to increase upon P-oxidation (6) (30.8 kcal mol(-1); same level of theory). Various ring-bond-activation processes were studied: N-protonation of P(III) (5) and P(V) (6, 7) derivatives leads to highly activated species that readily undergo P-N bond cleavage. In contrast, metal chlorides such as LiCl, CuCl, CuCl(2), BeCl(2), BCl(3), AlCl(3), TiCl(3), and TiCl(4) show little P-N bond activation in 5 and 7. Remarkably, TiCl(3) selectively activates the C-N bond, and induces stronger bond activation for P(V) (6, 7) than for P(III) azaphosphiridines (5). The ring-expanding rearrangement of P(V) azaphosphiridines 6-9 to yield P(III) 1,3,2-chalcogena-azaphosphetidines 32 a-d is predicted to be preferred for the heavier chalcogenides 7-9, but not for the P-oxide 6. The first comparative analysis of three bond strength parameters is presented: 1) the electron density at bond critical points, 2) Wiberg's bond index, and 3) the relaxed force constant. This reveals the usefulness of these parameters in assessing the degree of ring bond activation.

Synthesis and antiproliferative activity of a C,N-cycloplatinated(II) complex with a potentially intercalative anthraquinone pendant.

The synthesis of the novel anthraquinone platinum derivate [Pt(ppy)Cl(1C3)] (2) [Hppy = N,C-chelating 2-phenylpyridine; 1C3 = 1-[(3-aminopropyl)amino]-anthracene-9,10-dione] and its values of IC(50) against a panel of human tumor cell lines representative of ovarian (A2780 and A2780cisR) and breast cancers (T47D) are reported. At 24 h incubation time, complex 2 was more active than cisplatin (about 9-fold) and the free ligand 1C3 (about 2-fold) in T47-D. The observation that the cisplatin IC(50) falls by about 10-fold from 24 to 72 h, whereas that for 2 changes little, suggests substantial differences in the mode of action. Complex 2 also showed high cytotoxicity against A2780 (about 3-fold greater than cisplatin at 24 h). On the other hand, very low resistance factors (RF) of 2 in A2780cisR at 24-72 h (RF = 1.3) were observed. The interaction of 2 with DNA was followed by electrophoretic mobility and UV-visible spectroscopy, and its reaction with the model nucleobase 9-EtG was studied by (1)H NMR and ESI-MS. Theoretical calculations at the B3LYP/def2-TZVPP//BP86/def2-TZVP level of theory on complex 2 show a labile Pt-Cl bond that allows easy replacement of Cl by N-nucleophiles such as 9-EtG, which forms a stronger Pt-N bond.

A potent ruthenium(II) antitumor complex bearing a lipophilic levonorgestrel group.

The novel steroidal conjugate 17-α-[2-phenylpyridyl-4-ethynyl]-19-nortestosterone (LEV-ppy) (1) and the steroid-C,N-chelate ruthenium(II) conjugate [Ru(η(6)-p-cymene)(LEV-ppy)Cl] (2) have been prepared. At 48 h incubation time, complex 2 is more active than cisplatin (about 8-fold) in T47D (breast cancer) and also shows an improved efficiency when compared to its nonsteroidal analogue [Ru(η(6)-p-cymene)(ppy)Cl] (ppy = phenylpyridine) (3) in the same cell line. The act of conjugating a levonorgestrel group to a ruthenium(II) complex resulted in synergistic effects between the metallic center and the steroidal ligand, creating highly potent ruthenium(II) complexes from the inactive components. The interaction of 2 with DNA was followed by electrophoretic mobility. Theoretical density functional theory calculations on complex 2 show the metal center far away from the lipophilic steroidal moiety and a labile Ru-Cl bond that allows easy replacement of Cl by N-nucleophiles such as 9-EtG, thus forming a stronger Ru-N bond. We also found a minimum energy location for the chloride counteranion (4(+)·Cl(-)) inside the pseudocavity formed by the α side of the steroid moiety, the phenylpyridine chelating subsystem, and the guanine ligand, i.e., a host-guest species with a rich variety of nonbonding interactions that include nonclassical C-H···anion bonds, as supported by electrospray ionization mass spectra.

Synthesis, structural charaterization, and electrochemical and optical properties of ferrocene-triazole-pyridine triads.

The synthesis and electrochemical, optical, and cation-sensing properties of the ferrocene-triazole-pyridine triads 3 and 5 are presented. Azidoferrocene 1 and 1,1'-diazidoferrocene 4 underwent the "click" reaction with 2-ethynylpyridine to give the triads 3 and 5 in 81% and 68% yield, respectively. Electrochemical studies carried out in CH(3)CN in the presence of increasing amounts of Zn(2+), Ni(2+), Cd(2+), Hg(2+), and Pb(2+) metal cations, showed that the wave corresponding to the ferrocene/ferrocenium redox couple is anodically shifted by 70-130 mV for triad 3 and 167-214 mV for triad 5. The maximum shift of the ferrocene oxidation wave was found for 5 in the presence of Zn(2+). In addition, the low-energy band of the absorption spectra of 3 and 5 are red-shifted (Δλ = 5-10 nm) upon complexation with these metal cations. The crystal structures of compounds 3 and 5 and the complex [3(2)·Zn](2+) have been determined by single-crystal X-ray methods. (1)H NMR studies as well as density functional theory calculations have been carried out to get information about the binding sites that are involved in the complexation process.

Selective metal-cation recognition by [2.2]ferrocenophanes: the cases of zinc- and lithium-sensing.

The synthesis, electrochemical, optical, and cation-sensing properties of [2.2]ferrocenophanes, in which the two ferrocene subunits are linked through two aldiminic or iminophosphorane moieties, are reported. The new compounds show remarkably selective cation-sensing properties due to the presence of redox-active units (ferrocene) and aza-unsaturated functionalities that are able to act as putative cation-binding sites. In this structural motif, the aldimine groups act as a highly selective binding site for Zn(2+) cations, whereas the iminophosphorane bridges display an unusually strong binding affinity towards Li(+) cations, which could be explained by an additional LiFe interaction. The X-ray structure of the complex 4Li(+) as well as detailed NMR spectroscopic studies, both in solution and in the solid state, support this assessment. Experimental data and conclusions about the cation-sensing capabilities of this family of compounds are supported by DFT calculations.

Conformationally modulated intramolecular electron transfer process in a diaza[2,2]ferrocenophane.

A novel conformationally modulated Intramolecular Electron Transfer (IET) phenomenon has been observed due to the cyclic structure of the diaza[2.2]ferrocenophane 3. The corresponding mixed-valence compound of 3, prepared by electrochemical or chemical partial oxidation, interestingly shows the appearance of two absorption bands in the near infrared (NIR) spectral region. These bands are attributable to two intervalence charge-transfer transitions associated to two atropoisomers exhibiting different energy for the IET process. A solvent and temperature control over the atropoisomeric equilibrium have also been observed. The experimental data and conclusions about both the conformational and the electronic properties of compound 3 are also supported by density functional theory calculations.

Unexpected transalkylation on 3-alkyl-2-alkylthio-1,3,4-thiadiazolium-5-thiolates: a computational and experimental mechanistic study.

5-Alkylthio-3-methyl-2-thioxo-1,3,4-thiadiazolines have been obtained on heating alkyl 1-methyl-1-hydrazinecarbodithioates with CS(2). A DFT-based computational mechanistic study suggests an initial pseudopericyclic [1,4]H shift as a key step, as well as the intermediacy of the otherwise expected isomers 2-alkylthio-3-methyl-1,3,4-thiadiazolium-5-thiolates, from which the final products are formed by stepwise S,S-transalkylation.

Imidazole-annelated ferrocene derivatives as highly selective and sensitive multichannel chemical probes for Pb(II) cations.

New ferrocenyl-containing imidazopyridine and imidazophenazine receptors 2-5 show high selective affinity for Pb(II) ions over a range of other metal ions examined through different channels. Imidazopyridine-ferrocene dyad 2 behaves as a highly selective redox, chromogenic, and fluorescent chemosensor molecule for Pb(2+) cations: the oxidation redox peak is anodically shifted (DeltaE(1/2) = 150 mV), and the low energy band of the absorption spectrum is red-shifted (Deltalambda = 44 nm) upon complexation with this metal cation. This change in the absorption spectrum is accompanied by a color change from colorless to orange, which allows the potential for "naked eye" detection. The emission spectrum undergoes an important chelation-enhanced fluorescence (CHEF) effect (CHEF = 620), with an unprecedented detection limit of 2.7 microg L(-1). The presence of Zn(2+) cations also induced a perturbation of the redox potential, absorption, and emission spectra although in less extension than those found with Pb(2+) cations. Imidazophenazine-ferrocene dyad 3 has also shown its ability for sensing Pb(2+) cations through redox (DeltaE(1/2) = 120 mV), absorption (Deltalambda = 23 nm), and emission (CHEF = 133) channels, whereas the presence of Zn(2+) only has a little effect on the emission spectrum (CHEF = 74). The electrochemical changes observed in the two-armed ferrocenes 4 and 5 upon complexation show that the potential shift is higher for Zn(2+) ions (DeltaE(1/2) = 190-170 mV) than for Pb(2+) ions (DeltaE(1/2) = 180-110 mV), which is in clear contrast to those observed for the monoarmed ferrocenes 2 and 3. The recognition properties of the two-armed imidazopyridine-ferrocene triad 4 are quite similar to those exhibited by the parent monosubstituted receptor 2, and the most salient features are a strong perturbation of the redox wave (DeltaE(1/2) = 180 mV), a dramatic increasing of the fluorescent quantum yield (Phi(complex)/Phi(ligand) = 890) in the presence of Pb(2+), while the optical responses toward Zn(2+) cations were silent. The two-armed imidazophenazine-ferrocene triad 5 senses Pb(2+) cations through perturbation of the oxidation potential of the Fe(II)/Fe(III) redox couple (DeltaE(1/2) = 110 mV), important blue shift (Deltalambda = 160 nm) of the high energy band in the absorption spectrum, and a remarkable increase of the emission band (CHEF = 220), whereas smaller changes were observed in the presence of Zn(2+) cations. (1)H NMR studies as well as DFT calculations have been carried out to get information about which molecular sites are involved in the binding event.

A selective redox and chromogenic probe for Hg(II) in aqueous environment based on a ferrocene-azaquinoxaline dyad.

A new chemosensor molecule 4 based on a ferrocene-azaquinoxaline dyad effectively recognizes Hg(2+) in an aqueous environment as well as Pb(2+) and Zn(2+) metal cations in CH(3)CN solution through three different channels. Upon recognition, an anodic shift of the ferrocene/ferrocenium oxidation peaks and a progressive red shift (Deltalambda = 112-40 nm) of the low energy band, in their absorption spectra, is produced. These changes in the absorption spectra are accompanied by color changes from orange to deep green, for Hg(2+), and to purple in the cases of Pb(2+) and Zn(2+). Remarkably, the redox and colorimetric responses toward Hg(2+) are preserved in the presence of water (CH(3)CN/H(2)O, 3/7). The emission spectrum of 4 in CH(3)CN (lambda(exc) = 270 nm) undergoes important chelation enhancement of fluorescence (CHEF) in the presence of Hg(2+) (CHEF = 204), Pb(2+) (CHEF = 90), and Zn(2+) (CHEF = 184) metal cations. Along with the spectroscopic data, the combined (1)H NMR data of the complexes and the theoretical calculation suggest the proposed bridging coordination modes.

Mononuclear ferrocenophane structural motifs with two thiourea arms acting as a dual binding site for anions and cations.

The synthesis of a new type of mononuclear ferrocenophane-based thiourea, in which the ferrocene moiety is simultaneously attached to two thiourea groups directly from 1,1'-bis(isothiocyanato)ferrocene, is reported. These nitrogen-rich structural motifs show remarkable ion-sensing properties because of the presence of the redox active ferrocene unit and the thiourea bridges, which unexpectedly act as a dual binding site for anions and metal ions. They display a selective downfield shift of the thiourea protons and a remarkable cathodic shift of the ferrocene/ferrocenium redox couple with F(-), AcO(-), H(2)PO(4)(-), and HP(2)O(7)(3-) anions, whereas the selective recognition of Hg(2+) metal cations is achieved either by electrochemical or by spectral measurements. The preferred binding modes are proposed for the most representative complexes by means of density functional theory based theoretical calculations showing the Janus-like faces of the receptor.