A Theoretical Investigation of Two Typical Two‐Photon pH Fluorescent Probes

Intracellular pH plays an important role in many cellular events, such as cell growth, endocytosis, cell adhesion and so on. Some pH fluorescent probes have been reported, but most of them are one‐photon fluorescent probes, studies about two‐photon fluorescent probes are very rare. In this work, the geometrical structure, electronic structure and one‐photon properties of a series of two‐photon pH fluorescent probes have been theoretically studied by using density functional theory (DFT) method. Their two‐photon absorption (TPA) properties are calculated using the method of ZINDO/sum‐over‐states method. Two types of two‐photon pH fluorescent probes have been investigated by theoretical methods. The mechanisms of the Photoinduced Charge Transfer (PCT) probes and the Photoinduced Electron Transfer (PET) probes are verified specifically. Some designed strategies of good two‐photon pH fluorescent probes are suggested on the basis of the investigated results of two mechanisms. For the PCT probes, substituting a stronger electron‐donating group for the terminal methoxyl group is an advisable choice to increase the TPA cross section. For the PET probes, the TPA cross sections increase upon protonation.

[1]  C. Cramer,et al.  Universal solvation model based on solute electron density and on a continuum model of the solvent defined by the bulk dielectric constant and atomic surface tensions. , 2009, The journal of physical chemistry. B.

[2]  Christopher J Chang,et al.  Screening mercury levels in fish with a selective fluorescent chemosensor. , 2005, Journal of the American Chemical Society.

[3]  K. Belfield,et al.  A new water-soluble near-neutral ratiometric fluorescent pH indicator. , 2008, Organic letters.

[4]  M. Chesler.  Regulation and modulation of pH in the brain. , 2003, Physiological reviews.

[5]  Weiping Zhu,et al.  A highly sensitive and selective OFF-ON fluorescent sensor for cadmium in aqueous solution and living cell. , 2008, Journal of the American Chemical Society.

[6]  I Yuli,et al.  Cytosolic acidification as an early transductory signal of human neutrophil chemotaxis. , 1987, Science.

[7]  G. Stegeman,et al.  Two photon absorption of di‐alkyl‐amino‐nitro‐stilbene side chain polymer , 1994 .

[8]  L. Prodi,et al.  8-hydroxyquinoline derivatives as fluorescent sensors for magnesium in living cells. , 2006, Journal of the American Chemical Society.

[9]  Ping Li,et al.  A near-infrared neutral pH fluorescent probe for monitoring minor pH changes: imaging in living HepG2 and HL-7702 cells. , 2009, Journal of the American Chemical Society.

[10]  C. Fahrni,et al.  Metal Ion-Responsive Fluorescent Probes for Two-Photon Excitation Microscopy. , 2011, Chemistry of materials : a publication of the American Chemical Society.

[11]  H. Uramoto,et al.  Cellular pH regulators: potentially promising molecular targets for cancer chemotherapy. , 2003, Cancer treatment reviews.

[12]  Chuan-Feng Chen,et al.  New fluorescence-quenching process through resumption of PET process induced by complexation of alkali metal ion. , 2004, Organic letters.

[13]  Christopher J. Chang,et al.  A targetable fluorescent sensor reveals that copper-deficient SCO1 and SCO2 patient cells prioritize mitochondrial copper homeostasis. , 2011, Journal of the American Chemical Society.

[14]  P. Kinnunen,et al.  Elevated lysosomal pH in neuronal ceroid lipofuscinoses (NCLs). , 2001, European journal of biochemistry.

[15]  Yang Zhao,et al.  Theoretical study of solvent effect on one- and two-photon absorption properties of starburst DCM derivatives. , 2009, Physical chemistry chemical physics : PCCP.

[16]  R. Manderville,et al.  Biomarkers for phenol carcinogen exposure act as pH-sensing fluorescent probes. , 2007, Journal of the American Chemical Society.

[17]  K. Ohkubo,et al.  Phosphorescent sensor for biological mobile zinc. , 2011, Journal of the American Chemical Society.

[18]  D. A. Russell,et al.  Synthetic macrocyclic peptidomimetics as tunable pH probes for the fluorescence imaging of acidic organelles in live cells. , 2005, Angewandte Chemie.

[19]  Keli Han,et al.  Rational design of d-PeT phenylethynylated-carbazole monoboronic acid fluorescent sensors for the selective detection of alpha-hydroxyl carboxylic acids and monosaccharides. , 2009, Journal of the American Chemical Society.

[20]  S. Simon,et al.  Defective pH regulation of acidic compartments in human breast cancer cells (MCF-7) is normalized in adriamycin-resistant cells (MCF-7adr). , 1996, Biochemistry.

[21]  W. Webb,et al.  Multiphoton microscopy in biological research. , 2001, Current opinion in chemical biology.

[22]  H. Ågren,et al.  Charge-transfer Zn-porphyrin derivatives with very large two-photon absorption cross sections at 1.3-1.5 microm fundamental wavelengths. , 2005, The Journal of chemical physics.

[23]  J. Tusa,et al.  A fluorescent sensor with high selectivity and sensitivity for potassium in water. , 2003, Journal of the American Chemical Society.

[24]  F. Gan,et al.  Theoretical investigation on the one- and two-photon absorption properties for a series of symmetrical charge transfer fluorene–phenylene and fluorene–thiophene derivatives , 2006 .

[25]  Ji-Kang Feng,et al.  Theoretical investigation of one- and two-photon spectra of pyrazabole chromophores , 2011 .

[26]  K. Belfield,et al.  A New Water-Soluble Near-Neutral Ratiometric Fluorescent pH Indicator , 2007 .

[27]  W. Webb,et al.  Nonlinear magic: multiphoton microscopy in the biosciences , 2003, Nature Biotechnology.

[28]  R. Tsien,et al.  Digital image processing of intracellular pH in gastric oxyntic and chief cells , 1987, Nature.

[29]  Jianzhang Zhao,et al.  Chiral donor photoinduced-electron-transfer (d-PET) boronic acid chemosensors for the selective recognition of tartaric acids, disaccharides, and ginsenosides. , 2011, Chemistry.

[30]  L. Jullien,et al.  An efficient fluorescent probe for ratiometric pH measurements in aqueous solutions. , 2004, Angewandte Chemie.

[31]  Y. Eichen,et al.  Sensitive and selective PET-based diimidazole luminophore for Zn(II) ions: a structure-activity correlation. , 2006, Inorganic chemistry.

[32]  J. Tusa,et al.  A fluorescent chemosensor for sodium based on photoinduced electron transfer. , 2003, Analytical chemistry.

[33]  W. Denk,et al.  Deep tissue two-photon microscopy , 2005, Nature Methods.

[34]  X. You,et al.  Experimentation and theoretic calculation of a BODIPY sensor based on photoinduced electron transfer for ions detection. , 2009, The journal of physical chemistry. A.

[35]  H. Ågren,et al.  Effects of conjugation length, electron donor and acceptor strengths on two-photon absorption cross sections of asymmetric zinc-porphyrin derivatives. , 2006, The Journal of chemical physics.

[36]  Yang Zhao,et al.  A theoretical study on magnesium ion–selective two-photon fluorescent probe based on benzo [h] chromene derivatives , 2011 .

[37]  Evan W. Miller,et al.  A bright and specific fluorescent sensor for mercury in water, cells, and tissue. , 2007, Angewandte Chemie.

[38]  Seth R. Marder,et al.  Role of Dimensionality on the Two-Photon Absorption Response of Conjugated Molecules: The Case of Octupolar Compounds , 2002 .

[39]  Yi Luo,et al.  Influence of electron-acceptor strength on the resonant two-photon absorption cross sections of diphenylaminofluorene-based chromophores , 2003 .

[40]  W. Webb,et al.  Design of organic molecules with large two-photon absorption cross sections. , 1998, Science.

[41]  J. Tomasi,et al.  Electrostatic interaction of a solute with a continuum. A direct utilizaion of AB initio molecular potentials for the prevision of solvent effects , 1981 .

[42]  S. Lippard,et al.  Understanding zinc quantification with existing and advanced ditopic fluorescent Zinpyr sensors. , 2011, Journal of the American Chemical Society.

[43]  D. M. Bishop,et al.  Vibration and two-photon absorption , 2002 .

[44]  J. White,et al.  Two-photon imaging of spatially extended neuronal network dynamics with high temporal resolution , 2008, Journal of Neuroscience Methods.

[45]  T. Pons,et al.  Strong modulation of two-photon excited fluorescence of quadripolar dyes by (de)protonation. , 2004, Journal of the American Chemical Society.

[46]  Evan W. Miller,et al.  Preparation and use of Leadfluor-1, a synthetic fluorophore for live-cell lead imaging , 2008, Nature Protocols.

[47]  Jin Hee Hong,et al.  Two-photon fluorescent probes for acidic vesicles in live cells and tissue. , 2008, Angewandte Chemie.

[48]  Thierry Kogej,et al.  Mechanisms for enhancement of two-photon absorption in donor–acceptor conjugated chromophores , 1998 .

[49]  Brian J. Orr,et al.  Perturbation theory of the non-linear optical polarization of an isolated system , 1971 .

[50]  Yan Li Zhang,et al.  Donor−Acceptor-Substituted Anthracene-Centered Cruciforms: Synthesis, Enhanced Two-Photon Absorptions, and Spatially Separated Frontier Molecular Orbitals , 2009 .

[51]  B. Valeur,et al.  Molecular Fluorescence: Principles and Applications , 2001 .