Background: Fatty acid synthase (FAS), the key enzyme responsible for the synthesis of fatty acids, is weakly expressed in some normal human tissues. Recently, FAS has been demonstrated to be ...overexpressed in many non‐neoplastic highly proliferative lesions and in aggressive carcinomas with poor outcome, including colon, breast and ovary carcinomas.
Methods: In order to evaluate the prognostic significance of FAS in human melanoma, we analysed by means of immunohistochemistry, using a monoclonal anti‐FAS antibody, 77 primary melanomas and 30 nodal and cutaneous metastasis. Thirty nevi (15 dermal and 15 junctional nevi) were used as controls. All patients were followed‐up for 5 years.
Results: Thirty‐four melanomas expressed strong FAS immunostaining; the remaining 43 cases showed weak expression or were negative. All cutaneous and nodal metastasis were strongly positive. All patients with metastases deceased during the follow up period. Control specimens expressed weak staining. None of these patients developed recurrence. Statistical analysis revealed significant association of FAS expression with Breslow thickness (p = 0.012). The intensity of FAS immunostaining was also predictive of prognosis (p = 0.049).
Conclusions: FAS is a reliable prognostic marker in human melanomas. FAS predictive strength is increased when associated with Breslow thickness. The observation of FAS in human melanomas may stratify patients for stricter follow‐ups and suggest different therapeutic approaches.
We have investigated the formation of host–guest complexes between dendrimers of the poly(propylene amine) family functionalized with dansyl units at the periphery (hosts) with dye molecules ...(guests). Each dendrimer
nD
, where the generation number
n goes from 1 to 5, comprises 2
n+1
(i.e. 64 for
5D
) dansyl functions in the periphery and 2
n+1
−2 (i.e. 62 for
5D
) tertiary amine units in the interior. The most thoroughly investigated systems were those with eosin as a guest. The results obtained show that: (i) the
nD
dendrimers dissolved in dichloromethane solution extract eosin from aqueous solutions; (ii) the maximum number of eosin molecules hosted in the dendrimers increases with increasing dendrimer generation, up to a maximum of 12 for the
5D
dendrimer; (iii) the fluorescence of the peripheral dansyl units of the dendrimers is completely quenched via energy transfer by the hosted eosin molecules; (iv) the fluorescence of the hosted eosin molecules is partially quenched; (v) the eosin molecules can occupy two different sites (or two families of substantially different sites) in the interior of the dendritic structure; (vi) excitation of eosin hosted in the dendrimers causes sensitization of the dioxygen emission via eosin triplet excited state. The behavior of fluorescein and rose bengal is qualitatively similar to that of eosin, whereas naphthofluorescein is not extracted. The maximum number of dye molecules extracted by the
4D
dendrimer is 25 for rose bengal and ca. 1 for fluorescein, showing that the formation of host–guest species is related to the electronic properties rather than to the size of the dye molecules.
Combination of fluorescent dendritic hosts with fluorescent guests gives rise to quenching/sensitization processes that can be exploited for a variety of purposes. Fluorescence lifetime measurements has allowed us to establish that the dye molecules can occupy different sites in the interior of the dendritic structure.
By applying the three-dimensional template effect of copper(I), previously used for making various interlocking ring systems, a new disymmetrical 2-catenate has been made which consists of two ...different interlocking rings. One ring contains a 2,9-diphenyl-1,10-phenanthroline (dpp) unit whereas the other cycle incorporates both a dpp motif and a 2,2‘,6‘,2‘‘-terpyridine (terpy) fragment, the coordination site of these two chelates pointing toward the inside of the ring. Depending on the oxidation state of the central metal (Cu(I) or Cu(II)), and thus on its preferred coordination number, two distinct situations have been observed. With monovalent copper, the two dpp units interact with the metal and the terpy fragment remains free, at the outside of the molecule. By contrast, when the catenate is complexed to divalent copper, the terpy motif is bonded to the metal and it is now a dpp ligand which lies at the periphery of the complex. This dual coordination mode leads to dramatically different molecular shapes and properties for both forms. The molecular motion which interconverts the four- and the five-coordinate complexes can be triggered chemically, electrochemically, or photochemically by changing the oxidation state of the copper center (II/I). The process has been studied by electrochemistry and by UV-vis spectroscopy. Interestingly, once the stable 4-coordinate copper(I) complex has been oxidized to a thermodynamically unstable pseudo-tetrahedral copper(II) species, the rate of the gliding motion of the rings which will afford the stable 5-coordinate species (copper(II) coordinated to dpp and terpy) can be controlled at will. Under certain experimental conditions, the changeover process is extremely slow (weeks), and the 4-coordinate complex is more or less frozen. By contrast, addition of a coordinating counterion to the medium (Cl-) enormously speeds up the rearrangement and leads to the thermodynamically stable 5-coordinate complex within minutes.
Redox-Controllable Amphiphilic [2]Rotaxanes Tseng, Hsian-Rong; Vignon, Scott A.; Celestre, Paul C. ...
Chemistry : a European journal,
01/2004, Volume:
10, Issue:
1
Journal Article
Peer reviewed
With the fabrication of molecular electronic devices (MEDs) and the construction of nanoelectromechanical systems (NEMSs) as incentives, two constitutionally isomeric, redox‐controllable 2rotaxanes ...have been synthesized and characterized in solution. Therein, they both behave as near‐perfect molecular switches, that is, to all intents and purposes, these two rotaxanes can be switched precisely by applying appropriate redox stimuli between two distinct chemomechanical states. Their dumbbell‐shaped components are composed of polyether chains interrupted along their lengths by i) two π‐electron rich recognition sites—a tetrathiafulvalene (TTF) unit and a 1,5‐dioxynaphthalene (DNP) moiety—with ii) a rigid terphenylene spacer placed between the two recognition sites, and then terminated by iii) a hydrophobic tetraarylmethane stopper at one end and a hydrophilic dendritic stopper at the other end of the dumbbells, thus conferring amphiphilicity upon these molecules. A template‐directed protocol produces a means to introduce the tetracationic cyclophane, cyclobis(paraquat‐p‐phenylene) (CBPQT4+), which contains two π‐electron accepting bipyridinium units, mechanically interlocked around the dumbbell‐shaped components. Both the TTF unit and the DNP moiety are potential stations for CBPQT4+, since they can establish charge‐transfer and hydrogen bonding interactions with the bipyridinium units of the cyclophane, thereby introducing bistability into the 2rotaxanes. In both constitutional isomers, 1H NMR and absorption spectroscopies, together with electrochemical investigations, reveal that the CBPQT4+ ring is predominantly located on the TTF unit, leading to the existence of a single translational isomer (co‐conformation) in both cases. In addition, a model 2rotaxane, incorporating hydrophobic tetraarylmethane stoppers at both ends of its dumbbell‐shaped component, has also been synthesized as a point of reference. Molecular synthetic approaches were used to construct convergently the dumbbell‐shaped compounds by assembling progressively smaller building blocks in the shape of the rigid spacer, the TTF unit and the DNP moiety, and the hydrophobic and hydrophilic stoppers. The two amphiphilic bistable 2rotaxanes are constitutional isomers in the sense that, in one constitution, the TTF unit is adjacent to the hydrophobic stopper, whereas in the other, it is next to the hydrophilic stopper. All three bistable 2rotaxanes have been isolated as green solids. Electrospray and fast atom bombardment mass spectra support the gross structural assignments given to all three of these mechanically interlocked compounds. Their photophysical and electrochemical properties have been investigated in acetonitrile. The results obtained from these investigations confirm that, in all three 2rotaxanes, i) the CBPQT4+ cyclophane encircles the TTF unit, ii) the CBPQT4+ cyclophane shuttles between the TTF and DNP stations upon electrochemical or chemical oxidation/reduction of the TTF unit, and iii) folded conformations are present in which the CBPQT4+ cyclophane, while encircling the TTF unit, interacts through its π‐accepting bipyridinium exteriors with other π‐donating components of the dumbbells, especially those located within the stoppers.
“Clean” switching of three rotaxanes has been demonstrated in solution where the rotaxanes exist, to varying degrees, in folded conformations. They unfold under the influence of electrochemical stimuli (see scheme). The synthesis and characterization using photophysical, electrochemical and spectroscopic techniques are described for the bistable, redox‐controllable, 2rotaxane‐based molecular switches.
Five supramolecular systems containing the Ru(ttp){sub 2}{sup 2+} photosensitizer (P) covalently linked to an electron acceptor (A), MV{sup 2+}, and/or an electron donor (D), PTZ or DPAA, have been ...synthesized; ttp is 4{prime}-p-tolyl-2,2{prime}:6{prime},2{double prime}-terpyridine, MV{sup 2+} is methyl viologen, PTZ is phenotiazine, and DPAA is di-p-anisylamine. In the D-P-A triads the electron donor and acceptor groups are linked in opposite positions with respect to the photosensitizer. The spectroscopic properties (room-temperature absorption spectra, emission spectra and lifetimes in the 90-200 K temperature range, and transient absorption spectra and lifetimes at 150 K) and the (room-temperature) electrochemical behavior of the supramolecular systems and of their components have been investigated. At 90 K, where the solvent is frozen, no quenching of the photosensitizer luminescence is observed for all the supramolecular systems. At 150 K, where the solvent is fluid, the results obtained were as follows. In the PTZ-Ru(ttp){sub 2}{sup 2+} dyad, neither quenching of the photosensitizer luminescence nor formation of oxidized donor are observed. In the DPAA-Ru(ttp){sub 2}{sup 2+} dyad, luminescence quenching and transient formation of the oxidized donor take place. For the Ru(ttp){sub 2}{sup 2+}-MV{sup 2+} dyad, transient formation of the reduced acceptor is observed, but the lifetime of the photosensitizer luminescence increases, indicating that charge recombination leads back to the excited photosensitizer. The PTZ-Ru(ttp){sub 2}{sup 2+}-MV{sup 2+} triad behaves as the Ru(ttp){sub 2}{sup 2+}-MV{sup 2+} dyad. For the DPAA-Ru(ttp){sub 2}{sup 2+}-MV{sup 2+} triad, strong luminescence quenching is observed, and transient absorption spectroscopy shows that charge separation is followed by a very fast charge recombination reaction ({tau}<100 ns). Thermodynamic and kinetic aspects of the photoinduced electron-transfer processes are discussed.
Acid−Base Controllable Molecular Shuttles Ashton, Peter R; Ballardini, Roberto; Balzani, Vincenzo ...
Journal of the American Chemical Society,
11/1998, Volume:
120, Issue:
46
Journal Article
Peer reviewed
Two novel 2rotaxanes, comprised of a dibenzo24crown-8 (DB24C8) macroring bound mechanically to a chemical “dumbbell” possessing two different recognition sitesviz., secondary dialkylammonium (NH2 +) ...and 4,4‘-bipyridinium (Bpym2+) unitshave been synthesized by using the supramolecular assistance to synthesis provided by, inter alia, hydrogen bonding interactions. One of these rotaxanes bears a fluorescent and redox-active anthracene (Anth) stopper unit. NMR spectroscopy and X-ray crystallography have demonstrated that the DB24C8 macroring exhibits complete selectivity for the NH2 + recognition sites, i.e., that the 2rotaxanes exist as only one of two possible translational isomers. Deprotonation of the rotaxanes' NH2 + centers effects a quantitative displacement of the DB24C8 macroring to the Bpym2+ recognition site, an outcome that can be reversed by acid treatment. The switching processes have been investigated by 1H NMR spectroscopy and, for the Anth-bearing rotaxane, by electrochemical and photophysical measurements. Furthermore, it is possible to drive the DB24C8 macroring from the dumbbell's Bpym2+ unit, in the deprotonated form of the Anth-bearing rotaxane, by destroying the stabilizing DB24C8−Bpym2+ charge-transfer interactions via electrochemical reduction. The photochemical and photophysical properties of this rotaxane (in both its protonated and deprotonated states) have also been investigated.
We have investigated the spectroscopic and electrochemical behavior of symmetric and unsymmetric first-, second-, and third-generation dendrimers comprising an electron-acceptor 4,4‘-bipyridinium ...core (viologen type) and electron-donor 1,3-dimethyleneoxybenzene (Fréchet-type) dendrons. The quite strong fluorescence of the symmetrically and unsymmetrically disubstituted 1,3-dimethyleneoxybenzene units of the dendrons is completely quenched as a result of donor−acceptor interactions that are also evidenced by a low-energy tail in the absorption spectrum. In dichloromethane solution, the 4,4‘-bipyridinium cores of the investigated dendrimers are hosted by a molecular tweezer comprising a naphthalene and four benzene components bridged by four methylene units. Host−guest formation causes the quenching of the tweezer fluorescence. The association constants, as measured from fluorescence and 1H NMR titration plots, (i) are of the order of 104 M-1, (ii) decrease on increasing dendrimer generation, and (iii) are slightly larger for the unsymmetric than for the symmetric dendrimer of the same generation. The analysis of the complexation-induced shifts of the temperature-dependent 1H NMR signals of the host and guest protons confirms that the bipyridinium core is positioned inside the tweezer cavity and allows the conclusions that (i) shuttling of the tweezer from one to the other pyridinium ring is fast (ΔG ⧧ < 10 kcal/mol), (ii) in the case of the unsymmetric dendrimers, the less substituted pyridinium ring is preferentially complexed in apolar solvents, and (iii) complexation of the 4,4‘-bipyridinium core proceeds by clipping for the symmetric dendrimers and by threading in the case of unsymmetric ones. Host−guest formation causes a displacement of the first reduction wave of the 4,4‘-bipyridinium unit toward more negative potential values, whereas the second reduction wave is unaffected. These results show that the host−guest complexes between the tweezer and the dendrimers are stabilized by electron donor−acceptor interactions and can be reversibly assembled/disassembled by electrochemical stimulation.
We report the synthesis and photophysical properties of two different photonic devices. The first system describes dinuclear metal complexes with a rigid and linear bridging ligand (PAP) that ...contains an adamantane spacer. We discuss the correlation between the nature of the bridging ligand and the electrochemical as well as photophysical properties of the metal complexes. Two interesting observations can already be pointed out: (i) the lifetime of the intermediate electron-transfer product Ru
III–PAP–Os
II is very long (130 μs); and (ii) for the first time in a dinuclear Ru/Os system, the rate constant of energy transfer from the Ru(II) to the Os(II) unit is faster than the rate of the electron transfer from the Ru(II) to the Os(III) unit. The second system represents a photonic switch which is built up by two subunits, a rhenium complex as the active switching part and an anthracene moiety as detector. We discuss the synthesis, the reversibility of the switch and the energy transfer properties of the new system.
An interior of 18 amide groups and a periphery functionalized with 24 dansyl groups forms a light‐harvesting dendrimer which features intense absorption bands in the near‐UV spectral region and a ...strong fluorescence band in the visible region. Upon encapsulation of Nd3+ ions, the fluorescence of the dansyl groups is quenched and an intense sensitized near‐infrared emission of Nd3+ is observed. The associated energy transfer is shown in the cartoon.
We have synthesized two dendrimers (
4 and
5
) consisting of a 1,4,8,11-tetraazacyclotetradecane (cyclam) core appended with four dimethoxybenzene and eight naphthyl units (
4
) and 12 ...dimethoxybenzene and 16 naphthyl units (
5
). The absorption and luminescence spectra of these compounds and the changes taking place upon protonation of their cyclam core have been investigated. In acetonitrile-dichloromethane 1:1 v/v solution they exhibit three types of emission bands, assigned to naphthyl localized excited states (
λ
max=337 nm), naphthyl excimers (
λ
max ca 390 nm), and naphthyl-amine exciplexes (
λ
max=480 nm). The tetraamine cyclam core undergoes only two protonation reactions, whose constants have been obtained by fitting the spectral changes. Protonation not only prevents exciplex formation for electronic reasons, but also causes strong nuclear rearrangements in the cyclam structure which affect excimer formation between the peripheral naphthyl units of the dendrimers.
When cyclam (1,4,8,11-tetraazacyclotetradecane) is functionalised with naphthyl-terminated Frèchet-type drendrons, three different emission bands (naphthyl localized, excimer, and exciplex) are observed. The cyclam core can undergo mono- and di-protonation processes, which are accompanied by strong changes in the emission properties of the dendrimers.
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