[Show abstract][Hide abstract] ABSTRACT: The scientific review presents a condensed, all-inclusive evaluation of the design, synthesis, and biomedical application of the various small-molecule two-photon (TP) probes that have been published before December 2014. The review has focused on only the TP probes for which the properties have been clearly characterized and which produce high-quality two-photon microscopy (TPM) images in an effort to avoid an excessive number of references. The review starts by describing the fundamental concept of two-photon absorption (TPA), followed by a description of the organic solvent-based model studies that established the use of TPM in the biomedical field.
Chemical Reviews 05/2015; 115(11). DOI:10.1021/cr5004425 · 46.57 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We summarize the nonlinear optical (NLO) properties of octupolar molecules, crystals, and films developed in our laboratory. We present the design strategy, structure–property relationship, and second-order NLO properties of 1,3,5-trinitro- and 1,3,5-tricyano-2,4,6-tris(p-diethylaminostyryl)benzene (TTB) derivatives, TTB crystals, and films prepared by free-casting TTB in poly(methyl methacrylate) (PMMA). The first hyperpolarizability of TTB was fivefold larger than that of the dipolar analogue. Moreover, the TTB crystal showed unprecedentedly large second-harmonic generation (SHG). While TTB crystal films (20 wt% TTB/PMMA) on various substrates showed appreciable SHG values, the cylinder film exhibited much larger SHG values and large electro-optic (EO) coefficients. The large SHG values and EO coefficients, as well as the high thermal stability of the cylinder film, will make it a potential candidate for NLO device applications.
The Chemical Record 11/2014; 15(1). DOI:10.1002/tcr.201402013 · 5.49 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A two-photon probe for near-membrane zinc ions that can be excited by 800 nm femtosecond laser pulses and emit at 500 nm is reported. The probe can be easily loaded into cells and tissue slices to visualize near-membrane zinc ions in live cells and tissues for a long period of time through the use of two-photon microscopy.
Asian Journal of Organic Chemistry 07/2014; 3(10). DOI:10.1002/ajoc.201402112 · 3.32 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Ketene-forming elimination from 2-X-4-nitrophenyl furylwacetates (1a-d) promoted by R2NH-R2NH2+ in 70 mol % MeCN(aq) has been studied kinetically. When X = Cl and NO2, the reactions exhibited second-order kinetics as well as Bronsted beta = 0.37-0.54 and I vertical bar beta(lg)vertical bar = 0.31-0.45. The Bronsted beta decreased with a poorer leaving group and vertical bar beta(lg)vertical bar increased with a weaker base. The results are consistent with an E2 mechanism. When the leaving group was changed to a poorer one [X=H (1a) and OCH3 (1b)], the reaction mechanism changed to the competing E2 and E1cb mechanisms. A further change to the Elcb mechanism was realized for the reaction of la with i-Pr2NH/i-Pr2NH2+ in 70 mol % MeCN-30 mol % D2O. By comparing the kinetic results in this study with the existing data for ArCH2C(O)OC6H3-2-X-4-NO2, the effect of the beta-aryl group on the ketene-forming elimination was assessed.
Bulletin- Korean Chemical Society 07/2014; 35(7):2143-2147. DOI:10.5012/bkcs.2014.35.7.2143 · 0.80 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Copper ions play a crucial role in living systems as cofactors of numerous metalloenzymes. To quantitatively estimate the Cu(2+) concentration in human tissue, we have developed a two-photon (TP) probe with an internal reference (ACCu2) that shows significant TP action cross-section and high selectivity for Cu(2+) and can quantitatively estimate the Cu(2+) concentration in human colon tissues by dual-color two-photon microscopy (TPM) imaging with minimum interference from other competing metal ions or pH and minimum cytotoxicity and photostability problems. The Cu(2+) concentrations in human normal colon, polyp, and colon cancer tissues were found to be 8.3 ± 0.3, 13 ± 2, and 22 ± 3 μM, respectively. This result suggests that ACCu2 may be useful for the diagnosis of human colon cancer.
[Show abstract][Hide abstract] ABSTRACT: We report two-photon probes for Zn(2+) ions that can simultaneously detect cytosolic and mitochondrial Zn(2+) ions in live cells and living tissues at 115 mm depth by dual-color TPM imaging with minimum interference from other biologically relevant species.
[Show abstract][Hide abstract] ABSTRACT: Two-photon microscopy (TPM) is a new imaging tool that can detect biological targets deep inside a live tissue. To faciltate the use of TPM in biomedical research, a variety of two-photon (TP) probes for specific applications are needed. In this Forum Article, we describe the design strategy, photophysical properties, and biological imaging applications of a selection of our recent studies in the development of TP probes for metal ions. Small-molecule TP turn-on probes, organelle-targeted probes, and multicolor emissive probes for dual-color imaging are briefly reviewed.
[Show abstract][Hide abstract] ABSTRACT: Hydrogen sulfide (H2S) is a new member of gaseous transmitters, which protects various organs from oxidative stress. In this article, we report a ratiometric two-photon probe, TFCA, which can be excited by 750 nm femtosecond pulses, shows a 110-fold increase in the intensity ratio upon reaction with HS(-) and high selectivity for HS(-), and can visualize the total sulfide ([H2S] + [HS(-)]) distribution in live tissue by two-photon microscopy (TPM). We also developed a kinetic method to quantitatively estimate the total sulfide concentration ([H2S] + [HS(-)]) in live tissues. The kinetic method allowed us to measure the observed rate constants (kobs) for the sulfide-induced deazidation reaction of TFCA in live cells and tissues using TPM. The total sulfide concentration was calculated by using kobs = k2[HS(-)], with the k2 value determined in HEPES/EtOH (1/1, pH = 7.2), and [H2S]/[HS(-)] = [H(+)]/Ka. The total sulfide concentration was found to be nearly zero in HeLa cells and 4-7 µM in rat colon tissues.
[Show abstract][Hide abstract] ABSTRACT: Reactions of 4-nitrophenyl 2-thiophenecarboxylate (1a-e) with in 20 mol % DMSO (aq) have been studied kinetically. The order kinetics, = 0.88-0.98, and linear Hammett and Yukawa-Tsuno plots observed for these reactions indicate an addition-elimination mechanism in which the step is rate limiting. The value increased with a stronger electron-withdrawing 5-thienyl substituent, the Hammett plots are linear except for X = MeO, and Yukawa-Tsuno plots are linear with = 0.79-1.32 and r = 0.28-0.93, respectively. The value increased and r value decreased with a stronger nucleophile, indicating an increase in the electron density at the C=O bond and a decrease in the resonance demand. These results have been interpreted with enhanced N-C bond formation in the transition state with the reactivity increase.
Bulletin- Korean Chemical Society 07/2013; 34(7). DOI:10.5012/bkcs.2013.34.7.2036 · 0.80 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Hydrogen sulfide (H2S) is a multifunctional signaling molecule that exerts neuroprotective effects in oxidative stress. In this article, we report a mitochondria-localized two-photon probe (SHS-M2) that can be excited by 750 nm femtosecond pulses and ratiometrically detect H2S in live astrocytes and living brain slices using two-photon microscopy (TPM). SHS-M2 showed a bright two-photon excited fluorescence and a marked blue-to-yellow emission color change in response to H2S, low cytotoxicity with easy loading and minimum interference from other biologically relevant species including reactive sulfur, oxygen and nitrogen species, thereby allowing quantitative analysis of H2S level. Molecular TPM imaging with SHS-M2 in astrocytes reveals that there is a correlation between the ratiometric analysis and expression levels of cystathionine β-synthase (CBS), the major enzyme that catalyzes H2S production. In comparison to wild-type controls, the attenuated H2S production was observed in DJ-1 (a Parkinson's disease gene) knockout astrocytes and brain slices where CBS expression is decreased. These findings demonstrate that reduced H2S levels in astrocytes may contribute to the development of Parkinson's disease (PD), and SHS-M2 may be useful as a marker to detect a risk of neurodegenerative diseases including PD.
Journal of the American Chemical Society 06/2013; 135(26). DOI:10.1021/ja404004v · 12.11 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Elimination reactions of (1a-e) promoted by in 70 mol % MeCN(aq) have been studied kinetically. The reactions are second-order and exhibit Brnsted = 0.80-0.84 and = 0.39-0.42, respectively. For all leaving groups and bases employed in this study, the and values remained almost the same. The results can be described by a negligible interaction coefficient, , which describes the interaction between the base catalyst and the leaving group. The negligible pxy interaction coefficient is consistent with the mechanism. Change of the base-solvent system from /MeCN to -70 mol % MeCN(aq) changed the reaction mechanism from E2 to . Noteworthy was the relative insensitivity of the transition state structure to the reaction mechanism change.
Bulletin- Korean Chemical Society 04/2013; 34(4). DOI:10.5012/bkcs.2013.34.4.1030 · 0.80 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Two-photon microscopy (TPM), which uses two photons of lower energy as the excitation source, is a vital tool in biology and clinical science, due to its capacity to image deep inside intact tissues for a long period of time. To make TPM a more versatile tool in biomedical research, we have developed a variety of two-photon probes for specific applications. In this mini review, we will briefly discuss two-photon probes for lipid rafts, lysosomes, mitochondria, and pH, and their biomedical applications. [BMB Reports 2013; 46(4): 188-194].
[Show abstract][Hide abstract] ABSTRACT: Mitochondria provide the energy of the cells and are the primary site of oxygen consumption and the major source of reactive oxygen species. In mitochondria, metal ions and glutathione play vital roles in maintaining their structure and the redox environment. To understand their roles in mitochondria, it is crucial to monitor each of these chemical species in the mitochondria at the cell, tissue, and organism levels. An ideal tool for such purpose is the use of two-photon microscopy (TPM). Until recently, however, there has been no report on the two-photon (TP) probes suitable for such applications. In this paper, we summarize the mitochondria-targeted TP probes for Zn(2+), H(2)O(2), and thiols, as well as their bioimaging applications.
Oxidative Medicine and Cellular Longevity 01/2013; 2013:323619. DOI:10.1155/2013/323619 · 3.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Since detergent-resistant lipid rafts play important roles in multidrug resistance (MDR), their comprehensive proteomics could provide new insights to understand underlying molecular mechanism of MDR in cancer cells. In the present work, lipid rafts were isolated from MCF-7 and adriamycin-resistant MCF-7/ADR cells and their proteomes were analyzed by label-free quantitative proteomics. Polymerase I and transcript release factor (PTRF)/cavin-1 was measured to be upregulated along with multidrug-resistant P-glycoprotein (P-gp), caveolin-1 and serum deprivation protein response (SDPR)/cavin-2 in the lipid rafts of MCF-7/ADR cells. PTRF knockdown led to reduction in the amount of lipid rafts on the surface of MCF7/ADR cells as determined by cellular staining with lipid raft-specific dyes such as S-laurdan2 and FITC-conjugated cholera toxin B. PTRF knockdown also reduced MDR in MCF-7/ADR cells. These data indicate that PTRF is necessary for MDR in cancer cells via the fortification of lipid rafts.
Journal of Proteome Research 12/2012; 12(2). DOI:10.1021/pr300651m · 4.25 Impact Factor