Understanding Strong Two-Photon Absorption in π-Conjugated Porphyrin Dimers via Double-Resonance Enhancement in a Three-Level Model

Drobizhev, Mikhail; Stepanenko, Yuriy; Dzenis, Yuliya; Karotki, Aliaksandr; Rebane, Aleksander; Taylor, PM; Anderson, Harry L.

doi:10.1021/ja0445847

Cited by 272 publications

(231 citation statements)

References 22 publications

Supporting

Mentioning

216

Contrasting

Unclassified

Order By: Relevance

“…Porphyrin derivatives are often effective PDT agents, as exemplified by verteporfin and Photofrin 4 . Recently it has been found that the two-photon cross-section of a porphyrin can be increased 500-fold by forming a conjugated porphyrin dimer [19][20][21] , and that these dimers have high singlet oxygen yields 20,22 . Here we show that porphyrin dimers can be functionalised with polar substituents to give effective TPE-PDT drugs.…”

mentioning

confidence: 99%

Blood-vessel closure using photosensitizers engineered for two-photon excitation

et al. 2008

Self Cite

View full text Add to dashboard Cite

The spatial control of optical absorption provided by twophoton excitation (TPE) has led to tremendous advances in microscopy 1 and microfabrication 2 . Medical applications of TPE in photodynamic therapy (PDT) 3,4 have often been suggested 5-18 , but have been made impractical by the low twophoton cross-sections of photosensitiser drugs (i.e. compounds taken up by living tissues that become toxic on absorption of light). The invention of efficient two-photon activated drugs will allow precise manipulation of treatment volumes in three dimensions, to a level unattainable with current techniques. Here we present a new family of PDT drugs designed for efficient TPE, and use one of them to demonstrate selective closure of blood vessels via TPE-PDT in vivo. These conjugated porphyrin dimers have two-photon cross-sections that are more than two orders of magnitude greater than those of clinical photosensitisers 17 . This is the first demonstration of in vivo PDT using a photosensitiser engineered for efficient two-photon excitation.Photodynamic therapy is used to treat diseases characterised by neoplastic growth including various cancers, age-related macular degeneration (AMD) and actinic keratosis 3,4 . Cell death is induced by photoexcitation of a sensitiser, generally via production of singlet oxygen. In the absence of light the photosensitiser is benign, so systemic toxicity is rare and treatment may be repeated without acquired resistance. Two-photon excitation of the photosensitiser should allow greater precision than is attainable by conventional one-photon excitation, as a consequence of the quadratic dependence of TPE on the local light intensity -the amount of TPE is inversely proportional to the fourth power of the distance from the focus. In addition, the longer wavelengths associated with TPE allow treatment deeper into tissue, by minimising absorption from endogenous chromophores.High instantaneous photon densities are essential for two-photon excitation. Early TPE-PDT studies used nanosecond lasers, but the dominant effect was photothermal damage [5][6][7] . The advent of commercial femtosecond tuneable Ti:sapphire lasers has greatly facilitated the investigation of TPE-PDT, and the limiting factor has become the availability of suitable photosensitisers. The majority of chromophores possess low two-photon cross-sections, of the order of 1-100 Goeppert-Mayer units (1 GM = 10 -50 cm 4 s photon -1 ). For example, the two FDA-approved PDT photosensitisers, verteporfin and Photofrin (cross sections 50 GM and 10 GM respectively) 17 , are unlikely to be suitable for TPE-PDT, as the high light intensities needed to achieve a therapeutic effect are close to the thresholds for photothermal or photomechanical damage 18 .Several design strategies for TPE-PDT photosensitisers have been reported recently [11][12][13][14][15][16] , but few of these compounds have yet been studied in vitro 15 , and, to date, none have progressed to in vivo testing. Porphyrin derivatives are often effective PDT agents, as exemplified ...

show abstract

mentioning

confidence: 99%

Blood-vessel closure using photosensitizers engineered for two-photon excitation

et al. 2008

Self Cite

View full text Add to dashboard Cite

show abstract

“…Porphyrin dimers were previously shown to possess one of the highest two‐photon absorption (TPA) cross‐sections, which makes them desirable sensors for use with two‐photon excitation 29, 32, 33. One of the reasons for these exceptionally high values of TPA cross‐sections is the efficient conjugation over the whole length of the molecule 34, 35.…”

Section: Resultsmentioning

confidence: 99%

Tuning the Sensitivity of Fluorescent Porphyrin Dimers to Viscosity and Temperature

Vyšniauskas

Ding

Qurashi

et al. 2017

Chemistry A European J

Self Cite

View full text Add to dashboard Cite

Conjugated porphyrin dimers have emerged as versatile viscosity‐sensitive fluorophores that are suitable for quantitative measurements of microscopic viscosity by ratiometric and fluorescence lifetime‐based methods, in a concentration‐independent manner. Here, we investigate the effect of extended conjugation in a porphyrin‐dimer structure on their ability to sense viscosity and temperature. We show that the sensitivity of the fluorescence lifetime to temperature is a unique property of only a few porphyrin dimers.

show abstract

“…[45][46][47][48][49][50][51] Conjugated porphyrin dimers exhibit much larger third-order susceptibilities (g) than the corresponding porphyrin monomers, [49][50][51] thus Equation (3) implies that dimeric analogues of JR1 will display even higher sensitivities to electric field. Previous studies on voltagesensitive SHG dyes have focused entirely on styryl and retinal chromophores.…”

Section: Methodsmentioning

confidence: 99%

Porphyrins for Probing Electrical Potential Across Lipid Bilayer Membranes by Second Harmonic Generation

et al. 2013

Self Cite

View full text Add to dashboard Cite

Neurons communicate by using electrical signals, mediated by transient changes in the voltage across the plasma membrane. Optical techniques for visualizing these transmembrane potentials could revolutionize the field of neurobiology by allowing the spatial profile of electrical activity to be imaged in real time with high resolution, along individual neurons or groups of neurons within their native networks. [1,2] Second harmonic generation (SHG) is one of the most promising methods for imaging membrane potential, although so far this technique has only been demonstrated with a narrow range of dyes. [3] Here we show that SHG from a porphyrin-based membrane probe gives a fast electro-optic response to an electric field which is about 5-10 times greater than that of conventional styryl dyes. Our results indicate that porphyrin dyes are promising probes for imaging membrane potential.Studies of excitable cells, such as neurons and cardiac myocytes, require new methods for mapping changes in membrane potential, ideally with a voltage resolution of about 1 mV, a time resolution of 1 ms, and a spatial resolution of 1 mm. [1,2] Microelectrodes can be used to measure transmembrane potentials with excellent sensitivity and temporal resolution, but they do not provide subcellular spatial resolution. Fluorescent calcium indicators are widely used to probe membrane potential indirectly, through the intracellular Ca 2+ concentration. However, changes in calcium concentration do not accurately reflect voltage transients. [4] Fluorescent voltage-sensitive dyes were first developed 30 years ago, [5] and recent advances in the molecular design of these dyes [6][7][8][9][10] have made it possible to track the spatial evolution of action potentials. [11][12][13][14] Compared with fluorescence, SHG imaging has several advantages as a technique for probing membrane potential: [3,[15][16][17][18][19][20][21] SHG has a greater intrinsic sensitivity to electric fields than fluorescence, [19][20][21] and it is only produced by noncentrosymmetric molecules in noncentrosymmetric environments, thus making it ideal for probing interfaces such as lipid bilayers. Similar to twophoton-excited fluorescence, SHG is a two-photon nonlinear optical effect, and it brings the advantages of depth penetration associated with multiphoton microscopy. [22] The main disadvantage of SHG is that it often gives lower intensity than fluorescence; there is a need for the design of brighter, more voltage-sensitive SHG dyes. [3,23] Styryl dyes and retinal chromophores have been shown to exhibit voltage-sensitive SHG when localized in plasma membranes, [15,24] and the voltage sensitivity of their SHG is greater than that of their fluorescence. [19][20][21] Recently we reported that amphiphilic porphyrins such as JR1 exhibit strong SHG when localized in lipid membranes. [25] Here we compare the voltage sensitivity of the SHG from JR1 with that from three widely studied styryl dyes (FM4-64, di-4-ANEPPS, and RH237) in hemispherical lipid bilayers (HLBs). [15,26,27] ...

show abstract

Understanding Strong Two-Photon Absorption in π-Conjugated Porphyrin Dimers via Double-Resonance Enhancement in a Three-Level Model

Cited by 272 publications

References 22 publications

Blood-vessel closure using photosensitizers engineered for two-photon excitation

Blood-vessel closure using photosensitizers engineered for two-photon excitation

Tuning the Sensitivity of Fluorescent Porphyrin Dimers to Viscosity and Temperature

Porphyrins for Probing Electrical Potential Across Lipid Bilayer Membranes by Second Harmonic Generation

Contact Info

Product

Resources

About