17323-81-8

To investigate the "site effect" of pyridyl substituents on a pyrene core, four regioisomeric monopyridyl-pyrene (1-4) and five regioisomeric dipyridyl-pyrene (5-9) conjugates were synthesized and characterized and their structures confirmed by single-crystal X-ray diffraction. The photophysical properties and related frontier orbital features of these compounds have been studied both experimentally and theoretically and demonstrate the dependence of the properties of the compounds on the position of substitution of the pyridyl moieties connecting to the pyrene core. It was found that the absorption spectra of 2- A nd 4-substituted pyrene derivatives display similar and weak influence on the S2 a? S0 excitations, whereas they are quite different from those of 1-substituted isomers. The emission spectra of 1- A nd 4-substituted pyrenes are quite similar, whereas those of 2-substituted isomers display the largest bathochromic shift. The 1,6-disubstituted compound 5 exhibits a near-unity emission quantum yield in solution, which is nearly three times higher than those of other regioisomeric dipyridyl-pyrenes. In addition, the tetrasubstituted 1,6-dipyridyl-3,8-di-n-butyl-pyrene (10) exhibits the highest solid-state quantum yield of 0.24 among all of the 10 pyridyl-pyrenes prepared in this study.

Provided is a composition comprising one or more phenanthroquinazoline-core compounds having structure (I)wherein each of R 1 and R 2 is independently a substituted or unsubstituted phenyl group.

Despite advances with triplex-forming oligonucleotides, peptide nucleic acids, polyamides and-more recently-engineered proteins, there remains an urgent need for synthetic ligands that enable specific recognition of double-stranded (ds) DNA to accelerate studies aiming at detecting, regulating and modifying genes. Invaders, i.e., energetically activated DNA duplexes with interstrand zipper arrangements of intercalator-functionalized nucleotides, are emerging as an attractive approach toward this goal. Here, we characterize and compare Invaders based on 1-, 2- and 4-pyrenyl-functionalized O2′-alkylated uridine monomers X-Z by means of thermal denaturation experiments, optical spectroscopy, force-field simulations and recognition experiments using DNA hairpins as model targets. We demonstrate that Invaders with +1 interstrand zippers of X or Y monomers efficiently recognize mixed-sequence DNA hairpins with single nucleotide fidelity. Intercalator-mediated unwinding and activation of the double-stranded probe, coupled with extraordinary stabilization of probe-target duplexes (ΔTm/modification up to +14.0 °C), provides the driving force for dsDNA recognition. In contrast, Z-modified Invaders show much lower dsDNA recognition efficiency. Thus, even very conservative changes in the chemical makeup of the intercalator-functionalized nucleotides used to activate Invader duplexes, affects dsDNA-recognition efficiency of the probes, which highlights the importance of systematic structure-property studies. The insight from this study will guide future design of Invaders for applications in molecular biology and nucleic acid diagnostics.

A series of phosphate mono-, di-, and triesters with a common leaving group (LG) (2′-(2-phenoxy)1, 10-phenanthroline) was prepared, and the kinetics of decomposition of their Cu(II) complexes was studied in methanol at 25°C under sspH-controlled conditions. The Cu(II) complexes of 2-[2′-phenanthrolyl]phenyl phosphate (Cu(ll):6), 2-[2′- phenanthrolyl]phenyl methyl phosphate (Cu(II):7), and 2-[2′-phenanthrolyl] phenyl dimethyl phosphate (Cu(II):8) are tightly bound, having dissociation constants Kd -7 M, with the Cu(II) being in contact with the departing phenoxide. The sspH/rate profile for cleavage of Cu(II): 6 has a low sspH plateau (k0 = 6.3 × 10-3 s-1), followed by a bell-shaped maximum (kcatmax= 14.7 ± 0.4 s -1) dependent on two ionizations with sspK a3 and sspKa 21 = 7.8 ± 0.1 and 11.8 ± 0.2. The sspH/rate profile for cleavage of Cu(ll):7 has a broad plateau from sspH 3 to sspH 10 followed by a descending wing at higher sspH with a gradient of -2. The s spH/rate profile for cleavage of Cu(ll):8 is sigmoidal with two plateaus (Zc1 = (2.0 ± 0.2) × 10-5S-1, k 2 = (1.2 ±0.2) × 10-6S-1), connected by an ionization with a sspKa of 6.03. Activation parameters are given for the reactions in the plateau regions: all three species show similar ΔH# terms of 21.4-21.6 kcal/mol, with major differences in the ΔS- terms, which vary from 18 to 2.3 to -7.4 cal/(mol-K) passing from the mono- to di- to triester. Detailed analyses of the kinetics indicate that the reactions involve spontaneous solvent-mediated cleavage of the Cu(ll)-coordinated phosphate dianion [Cu(ll):6b]° and phosphate diester monoanion [Cu(ll):7b]+ and, for the triester, complexes containing Cu(II) and Cu(II): -OCH 3 designated as [Cu(ll):8a]2+ and [Cu(ll):8b]+. Reactions where methoxide is the active nucleophile are not observed. Comparisons of the rates of the decomposition of these species at their sspH maxima in the neutral sspH region with the estimated rates of the background reactions indicate that leaving group assistance provided by the coordinated Cu(II) accelerates the cleavage of the phosphate mono-, di-, and triesters by 1014 to 1015, 1014, and 105. Detailed Hyperquad 2000 analysis of titration data indicates that phenoxide 9- is bound 23 kcal/mol stronger than the phosphate triester 8. It is the realization of part of this energy in the emerging products resulting from P-O(LG) cleavage that provides the driving force for the catalyzed reactions.

Compounds of formula (IIa): are provided where:X is a group capable of being cleaved from the α-carbon atom to form an ion of formula (I')C is a carbon atom bearing a single positive charge or a single negative charge; The invention further provides compounds of formula (IIb): where:X is a counter-ion to C. The compounds of formula (IIa) and (IIb) may form ions of formula (I') by either cleaving the C-X bond between X and the α-carbon atoms in the case of the compounds of formula (IIa) or dissociating X in the case of compounds of formula (IIb).

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