Electronic effects of conjugated aryl groups on the properties and reactivities of di(arylethynyl)tetracenes.

The photochemical oxidations of acenes can cause challenges with their optoelectronic applications, such as singlet fission and organic transistors. At the same time, these reactions form the basis for many luminescent sensing schemes for 1O2. While diethynyl substitution is arguably the most widely adopted of the various substitution strategies to control oxidation and also improve solubility and processability of long acenes, the extent to which differences between the alkyne groups can influence key properties of long acenes remains largely unknown. This report therefore describes the effects of various arenes and heteroarenes on the electronic structures, optical properites, and reactivity with singlet oxygen for eight 5,12-di(arylethynyl)tetracenes. The fluorescence spectra of these tetracenes span approximately 100 nm, while their observed rate constants for reaction with singlet oxygen correlates strongly with the HOMO level, spanning one order of magnitude. They are also amenable to fluorescent materials that respond ratiometrically to singlet oxygen. Therefore, electronic effects of groups directly conjugated to ethynylacenes offer a useful chemical space for rational acene design.

Substituent Effect in Pyridinium Alkynylanthracenes on their Performance as Photosensitizers for Photodynamic Therapy.

Progress in photodynamic therapy (PDT) relies on the design and synthesis of photosensitizers that can efficiently sensitize singlet oxygen using visible light irradiation while displaying limited dark toxicity. Here, we highlight the paper by Linker and coworkers published in this issue of Photochemistry and Photobiology, which evaluates the effect of the regiochemistry of pyridinium rings in three isomeric pyridinium alkynylanthracenes on their performance as photosensitizers for PDT in HeLa cells.

Red-Emitting, Acene-Doped Conjugated Polymer Nanoparticles that Respond Ratiometrically to Photogenerated 1O2.

Fluorophores that respond to external stimuli on demand have numerous applications in imaging and chemical or biological sensing. In this paper, we describe conjugated polymer nanoparticles (CPNs) that comprise a donor polymer matrix and a red-fluorescent, singlet oxygen-reactive heteroacene dopant (DE-TMT) that display a ratiometric response upon photo-oxidation. This ratiometric response can be tuned by the level of doping of DE-TMT, the identity of the conjugated polymer matrix used, and the blending of two conjugated polymers together to access red-shifted emission wavelengths. We followed a rational design process that combined (i) fundamental understanding of the influence of the chemical structure on luminescence spectra and efficiencies, energy transfer efficiencies, and reactivity and (ii) systematically determining how blending multiple chromophores in nanoparticles influences energy transfer efficiencies and the speed of optical responses to irradiation. Our approach of refining the compositions of these nanoparticles has yielded materials that combine many desirable characteristics for analytical applications-utility in aqueous environments, high quantum yield, emission of red light, and ratiometric luminescent responses. We anticipate that the type of approach described herein can be of use to others in designing CPNs for luminescence applications.

Acenes beyond organic electronics: sensing of singlet oxygen and stimuli-responsive materials.

The spectroscopic, electronic, and geometrical properties of acenes have enabled their broad applicability in organic optoelectronics. Beyond these physical characteristics of acenes, acenes also offer characteristic and predictable reaction chemistry, especially their behavior as dienes in cycloaddition reactions. Although these cycloaddition reactions, especially those with singlet oxygen (1O2) as the dienophile, are detrimental for organic electronics, this reactivity has led to several different applications such as sensing of 1O2, the release of cytotoxic reactive oxygen species (ROS), and stimuli-responsive materials for drug delivery. The rational design of acenes in these chemically-responsive applications beyond organic optoelectronics requires an understanding of how chemical structure influences both the physical properties, such as quantum yield of emission, as well as the reactivity of acenes and their cycloadducts. Therefore, the objective of this review is to summarize how cycloaddition reactions of acenes have expanded their applications in different areas of materials chemistry, and in doing so inspire and inform the rational design of acene-based materials with applications beyond organic electronics.

Spectroscopy and Reactivity of Dialkoxy Acenes.

Photochemical oxidation of acenes can benefit or impede their function, depending on the application. Although acenes with alkoxy substituents on reactive sites are important for applications as diverse as drug delivery and organic optoelectronics, the influence of chemical structure on their photochemical oxidation remains unknown. This paper therefore describes the synthesis, spectroscopic properties, and reactivity with singlet oxygen (1 O2 ) of a series of dialkoxyacenes that vary in the number and types of fused rings in the (hetero)acene cores. Reductive alkylation of quinone precursors yielded target dialkoxyacenes with fused backbones ranging from benzodithiophene to tetracenothiophene. Trends of their experimental spectroscopic characteristics were consistent with time-dependent density functional theory (TD-DFT) calculations. NMR studies show that photochemically generated 1 O2 oxidizes all but one of these acenes to the corresponding endoperoxides in organic solvent. The rates of these oxidations correlate with the number and types of fused arenes, with longer dialkoxyacenes generally oxidizing faster than shorter derivatives. Finally, irradiation of these acenes in acidic, oxidizing environments cleaves the ether bonds. This work impacts those working in organic optoelectronics, as well as those interested in harnessing photogenerated reactive oxygen species in functional materials.

Polymer Amphiphiles for Photoregulated Anticancer Drug Delivery.

We report the synthesis of amphiphilic polymers featuring lipophilic stearyl chains and hydrophilic poly(ethylene glycol) polymers that are connected through singlet oxygen-cleavable alkoxyanthracene linkers. These amphiphilic polymers assembled in water to form micelles with diameters of ∼20 nm. Reaction of the alkoxyanthracene linkers with light and O2 cleaved the ether C-O bonds, resulting in formation of the corresponding 9,10-anthraquinone derivatives and concomitant disruption of the micelles. These micelles were loaded with the chemotherapeutic agent doxorubicin, which was efficiently released upon photo-oxidation. The drug-loaded reactive micelles were effective at killing cancer cells in vitro upon irradiation at 365 nm, functioning through both doxorubicin release and photodynamic mechanisms.

High-Throughput Assay for Enantiomeric Excess Determination in 1,2- and 1,3-Diols and Direct Asymmetric Reaction Screening.

A simple and efficient method for determination of the yield, enantiomeric/diasteriomeric excess (ee/de), and absolute configuration of crude chiral diols without the need of work-up and product isolation in a high throughput setting is described. This approach utilizes a self-assembled iminoboronate ester formed as a product by dynamic covalent self-assembly of a chiral diol with an enantiopure fluorescent amine such as tryptophan methyl ester or tryptophanol and 2-formylphenylboronic acid. The resulting diastereomeric boronates display different photophysical properties and allow for fluorescence-based ee determination of molecules containing a 1,2- or 1,3-diol moiety. This method has been utilized for the screening of ee in a number of chiral diols including atorvastatin, a statin used for the treatment of hypercholesterolemia. Noyori asymmetric hydrogenation of benzil was performed in a highly parallel fashion with errors <1 % ee confirming the feasibility of the systematic examination of crude products from the parallel asymmetric synthesis in real time and in a high-throughput screening (HTS) fashion.

Toward Fluorescence-Based High-Throughput Screening for Enantiomeric Excess in Amines and Amino Acid Derivatives.

A highly accurate and reliable screening method for enantiomeric excess of amine derivatives in the presence of water is reported. The fluorescence-based screening system has been realized by self-assembly of chiral diol-type dyes (BINOL, VANOL and VAPOL), 2-formylphenylboronic acid, and chiral amines forming iminoboronate esters. The structure and chirality of the amine analytes determine the stability of the diastereomeric iminoboronate esters, which in turn display differential fluorescence. The fluorescence signal reflects the enantiomeric purity of the chiral amines and was utilized in high-throughput arrays. The arrays were able to recognize enantiomeric excess of amines, amino esters, and amino alcohols. In addition to qualitative analysis, quantitative experiments were successfully performed. Studies of the role of additives such as water or citrate were carried out to gain insight into the stability of the iminoboronate esters. It is shown that the above additives destabilize less stable esters while the stable esters remain unchanged. Thus, the presence of water and citrate leads to increased difference between the diastereomeric iminoboronates and contributes to the enantiodiscrimination of the chiral amines.

Determination of enantiomeric excess in amine derivatives with molecular self-assemblies.

We report the first fluorescence-based assay for the rapid determination of the ee value of amines, amino alcohols, and amino acid esters. The method uses the self-assembly of 2-formylphenylboronic acid with a chiral diol and a chiral amine or derivatives (of unknown chirality) to produce two diastereomeric iminoboronates that differ in their fluorescence intensity and polarization. The approach allows for the accurate determination of the ee value of chiral amines with errors of just 1-2%. We believe that this application of orthogonal dynamic covalent self-assembly in the determination of the enantioselectivity will lead to the development of high-throughput procedures for the determination of chirality.

Multi-responsive metal-organic lantern cages in solution.

Soluble copper-based M4L4 lantern-type metal-organic cages bearing internal amines were synthesized. The solution state integrity of the paramagnetic metal-organic cages was demonstrated using NMR, DLS, MS, and AFM spectroscopy. 1D supramolecular pillars of pre-formed cages or covalent host-guest complexes selectively formed upon treatment with 4,4'-bipyridine and acetic anhydride, respectively.

Dicopper double-strand helicates held together by additional π-π interactions.

The bis-bidentate ligand, obtained from Schiff base condensation of RR-1,2-cyclohexanediamine and 8-naphthylmethoxyquinoline-2-carbaldehyde (L-L), forms with [Cu(I)(MeCN)4]ClO4 a double strand helicate complex, made especially stable by the presence of four definite interstrand π-π interactions involving a quinoline subunit and a naphthylmethoxy substituent of the two strands. The [Cu(I)2(L-L)2](2+) complex, which does not decompose even on excess addition of either L-L or Cu(I), undergoes a two electron oxidation in MeCN, through two one-electron fully reversible steps, separated by 260 mV, as shown by cyclic voltammetry (CV) studies. The high stability of the mixed valence complex [Cu(I)Cu(II)(L-L)2](3+) with respect to disproportionation to [Cu(I)2(L-L)2](2+) and [Cu(II)2(L-L)2](4+) is essentially due to a favorable electrostatic term. Cu(II) forms with L-L a stable species, with a 1:1 stoichiometric ratio, but, in the absence of crystallographic data, it was impossible to assess whether it is of mono- or dinuclear nature. However, CV studies on an MeCN solution containing equimolar amounts of Cu(II) and L-L showed the presence in the reduction scan of two fully reversible waves, separated by about 250 mV, which indicated the presence in solution of a dicopper(II) double strand helicate complex, [Cu(II)2(L-L)2](4+). This work demonstrates that additional interstrand π-π interactions can favor the formation of unusually stable dicopper(I) and dicopper(II) helicate complexes.

Sulfate-templated self-assembly of new M4L6 tetrahedral metal organic cages.

Six equivalents of N,N'-bis(4-aminobenzyl)urea, 12 equivalents of 2-formylpyridine and four equivalents of FeSO(4) or NiSO(4) undergo subcomponent self-assembly in aqueous solution to form tetrahedral cages around a single, encapsulated sulfate anion.

Octahedral copper(II) and tetrahedral copper(I) double-strand helicates: chiral self-recognition and redox behavior.

The racemic form of 5 ((RR)5 + (SS)5) gives dinuclear complexes of 2:2 stoichiometry both with Cu(II), acting as a bis-terdentate ligand, and with Cu(I), acting as a bis-bidentate ligand. Single crystal X-ray diffraction studies have shown that the Cu(II) complex exists as double-strand homochiral helicate molecules: P,P-[Cu(2)(II)((RR)5)(2)](4+) and M,M-[Cu(2)(II)((SS)5)(2)](4+); in which the two trans-1,2-cyclohexanediamine subunits have the same chirality for of the two strands. Each Cu(II) metal center is six-coordinated according to a cis-octahedral geometry and interacts with a NNO donor subunit of each strand. The Cu(I) complex, when crystallized from THF in the presence of (rac)5, gives a double-strand homochiral helicate complex and in the solid state forms a racemic mixture of the homochiral metal complexes M,M-[Cu(2)(I)((RR)5)(2)](2+) and P,P-[Cu(2)(I)((SS)5)(2)](2+). When crystallizing from a MeCN solution, Cu(I) and (rac)5 give rise to the heterochiral nonhelicate dimeric complex [Cu(2)(I)((RR)5)((SS)5)](2+), in which the two strands of the dimer have inverse configuration of the trans-1,2-cyclohexanediamine subunits and are assembled side-by-side. In both structural architectures, the Cu(I) centers are four-coordinated by two nitrogen atoms from each strand, according to a distorted tetrahedral geometry. In MeCN solution, the dinuclear Cu(II) complex disassembles to give the mononuclear species, which, on reduction at a platinum electrode in a cyclic voltammetry experiment, gives two Cu(I) mononuclear complexes that quickly assemble to give the dinuclear Cu(I) complex. This complex undergoes two consecutive one-electron oxidation processes, but the dinuclear Cu(II) species that forms decomposes in less than 1 s. On the contrary, the [Cu(2)(I)((rac)5)(2)](2+) complex is stable in MeCN solution and undergoes two one-electron oxidation processes to give a form of dinuclear Cu(II) complex that lasts in solution for more than 20 s.