Sirbu Dumitru

A selection of NIR-optically responsive neuron probes was produced comprising of a donor julolidyl group connected to a BODIPY core and several different styryl and vinylpyridinyl derived acceptor moieties. The strength of the donor-acceptor interaction was systematically modulated by altering the electron withdrawing nature of the aryl unit. The fluorescence quantum yield was observed to decrease as the electron withdrawing effect of the aryl subunit increased in line with changes of the Hammett parameter. The effectiveness of these fluorophores as optically responsive dyes for neuronal imaging was assessed by measuring the toxicity and signal-to-noise ratio (SNR) of each dye. A great improvement of SNR was obtained when compared to the first-generation BODIPY-based voltage sensitive dyes with concomitant toxicity decrease. The mechanism for the optical response is disparate from conventional cyanine-based dyes, opening up a new way to produce effective voltage sensitive dyes that ...

Ferrocene is one of the most widely established compounds in the chemical literature, and it is frequently used as a starting material in both organometallic and organic chemistry transformations. 1 This sandwich-type compound consists of an iron(II) atom bonded in an   fashion to two cyclopentadienide rings (Cp). Redox cycling between the Fe 2+ /Fe 3+ states is both chemically and electrochemically reversible. 2 Certainly this final point is one main reason why ferrocene has been so popular as a redox reporter in supramolecular structures. 3 The Cp rings are aromatic and hence it is possible to perform typical electrophilic substitution reactions on one or both of the rings. 4 Selective reactions on a single Cp ring to introduce two disparate functional groups (e.g. PPh 2 , dihydrooxazole) is also possible. 5 For this latter case the ferrocene subunit is used as a planar chiral ligand for asymmetric catalysis applications. 6 For each ring to incorporate a different functional group can be complex, often requiring selective BuLi reactions at low temperatures. 7 A long reaction time and a convoluted purification method is possible starting from 1,1′-ferrocenedicarboxaldehyde. 8 A very mild and fast method to achieve a similar outcome would appear to be appealing, provided the two functional groups are useful for further reactions. 9 It turned out that, as part of our research effort into producing ferrocene-based porphyrin and borondipyrromethene (Bodipy) compounds, we discovered such a simple procedure. The oxidation of ferrocenecarboxaldehyde using aqueous KMnO 4 in acetone is well documented to produce the corresponding carboxylic acid. 10 Repeating the literature method afforded ferrocenecarboxylic acid in reasonable yield. However, we found that the same procedure applied to 1,1′-ferrocenedicarboxyaldehyde in acetone or acetonitrile did not produce the corresponding dicarboxylic acid (Scheme 1). The 1 H NMR spectrum for the major product isolated from the acetonitrile reaction showed different resonances for the two Cp rings, confirming the product to be unsymmetrical. Furthermore, two downfield resonances at  193.21 and 170.77 for the 13 C{ 1 H} NMR spectrum were consistent with the presence of aldehyde and carboxylic acid groups. The mass spectrum showed a peak at m/z 259, and a broad peak at ca. 2939 cm 1 in the FT-IR spectrum confirmed production of a carboxylic acid group. The combined evidence verified the product to be compound 1, in which one aldehyde was oxidized but the other remained untouched. Hence, under these conditions the ferrocene is desymmetrized since it contains two different functional groups. The overall yield for 1 is 49% after a fast and chromatography-free work up, providing material pure enough for further synthetic reactions. A similar reaction performed using an acetone/H 2 O mixture (ca. 1:1) did not afford a product with a 1 H NMR spectrum consistent with compound 1. Instead, additional resonances were observed in the olefinic region ( = 7.35 and 6.30, J = 16.2 Hz), a methyl resonance ( = 2.25) and a downfield resonance ( = 197.51) in the 13 C NMR spectrum, which is consistent with the existence of a CH 3 CO group (see Supporting Information). 11 The mass spectrum showed a peak at m/z 299, and once again the FT-IR spectrum corroborated the presence of a carboxylic acid (2934 cm 1). 12 The spectroscopic data are fully consistent with compound 2 with a trans double bond. We speculate that oxidation of one aldehyde to the carboxylic acid activates the other carbonyl in 1 to a condensation reaction with the acetone present in solution. Presumably for ferrocenecarboxaldehyde the reaction of the aldehyde with acetone is too slow to compete with oxidation. Rather surprisingly, compounds 1 and 2 could not be found in the literature using popular search tools (i.e., Scifinder, Reaxys). The closest analogue to 2 is the structural isomer (C 15 H 14 FeO 3) in which one ring has a formyl and the other the (E)--(methoxycarbonyl)ethenyl subunit. 8 This material was produced by a controlled Wittig reaction with 1,1′-ferrocenedicarboxaldehyde, yielding a mixture of compounds which had to be separated by chromatography. Again for compound 1 the structural analogue (C 12 H 10 FeO 3) has both the formyl and carboxylic acid substituted on the same Cp ring. 13 Scheme 1. Reagents and Conditions: (i) KMnO 4 , CH 3 CN/H 2 O, 0 °C; (ii) KMnO 4 , acetone/H 2 O, 0 °C. Scheme 2. Reagents and Conditions: (i) 2-acetylpyridine, aq. NaOH/NH 4 OH, dark; (ii) (a) diethyl malonate, NaOEt, EtOH; (b) H 2 O, H + .

Two Chromophore-Quencher Conjugates (CQCs) have been synthesized by covalent attachment of the anti-oxidant dibutylated-hydroxytoluene (BHT) to a pyrrole-BF2 chromophore (BOPHY) in an effort to protect the latter against photofading. In fluid solution, light-induced intramolecular charge transfer is favoured in polar solvents and helps to inhibit photo-bleaching of the chromophore. The rate of photo-fading, which scales with the number of BHT residues, is zero-order in polar solvents but shows a linear dependence on the number of absorbed photons. The zero-order rate constant shows an inverse correlation with the fluorescence quantum yield measured in the same solvent. Photo-bleaching in benzonitrile involves autocatalysis while reaction in cyclohexane shows an unexpected stoichiometry. NMR spectroscopy indicates initial damage takes place at the BHT unit and allows identification of a reactive hydroperoxide as being the primary product. In the presence of an adventitious substrate, this hydroperoxide is a photocatalyst for amide formation under mild conditions.