Process technology for synthesising efficient Pyrromethene (PM) laser dyes such as PM567 and PM597 has been developed.These are useful for high average power and high repetition rate dye lasers. Also,PM dyes are potential candidates to be used as chemosensors, bio-labelling and in photodynamic therapy.

Salient Features

• Highly fluorescent dyes.
• Very high extinction coefficients.
• High lasing efficiency.
• Wide spectral range (550-610 nm) for dye laser application.
• Good solubility in common organic solvents (EtOH, MeOH etc.)
• Dye lasers may be pumped by both second harmonic of Nd-YAG (at 532 nm) and green output of CVLs (at 511 nm) or DPSSGLs (at 532 nm).
• Highly Cost effective compared to imported products

A gain medium in an optical resonator cavity is needed for generating Laser Beam in visible/ non visible spectrum. Some of the common mediums, solid, liquid or gas, used are Ruby, CO2, CVL, Nd:YAG. Ti:Sa etc. Advantage of Dye Laser technology is that we can devise a gain  medium by dispersing this highly fluorescent dye in liquids, glass, polymer etc. also and generate tunable laser wavelengths, generally in the visible spectrum.
Process technology for synthesising efficient BODIPY or Pyrromethene (PM) laser dyes such as PM567 and PM597 has been developed. These PM dyes are efficiently used in high repetition rate (~10 kHz), high average power dye lasers. Also, PM dyes are potential candidates to be used as chemosensors, bio-labelling and in photodynamic therapy.

1. Preamble

Despite existing for almost a century, fluorescent dyes continue to attract the attention of scientists from an ever expanding multidisciplinary arena. Recent developments in the field of personal diagnostics and in the area of organic electroluminescent devices have boosted interest in the development of next-generation emissive dyes. Countless classes of highly fluorescent organic compounds are now known, but the difluoro-boraindacene family (4,4-difluoro-4-borata-3a-azonia-4a-aza-s-indacene, abbreviated hereafter as BODIPY, also called Pyrromethene) has gained recognition as being one of the more versatile fluorophores and steadily increased in popularity over the past two decades [1]. The first member of this class of compound was reported by Treibs and Kreuzer in 1968 [2], although relatively little attention was given to the discovery until the end of the 1980s [3]. During the late 1980s and early 1990s,Boyer and co-workers established BODIPY dyes as a new class of laser dyes with emission covering the spectral region from the green yellow to the red [4]. Their high fluorescence yields in conjunction with excellent lasing efficiencies, intense absorption profiles in the green spectral region and low triplet-triplet extinction coefficients over the entire fluorescence region are the major attractions for the dye laser scientist [5]. These are zwiter-ionic dyes exhibiting good solubility in many organic solvents and even in methyl methacrylate (MMA) that is useful for solid state dye laser applications [6a-d]. Some of the Pyrromethene (PM) dyes outperform the widely used laser dye, rhodamine 6G (Rh6G), considered as the benchmark in lasing efficiency and photochemical stability.

Subsequently, the potential use of these dyes for biological labelling was recognized [6], and several new PM-based dyes were designed and even commercialized for biological application . As a consequence, PM dyes came to be known to the biochemist and biologist as a photostable substitute for fluorescein, and the number of papers and patents started to escalate in the mid 1990s. The use of PMs as effective biological label has been complemented by their propensity to function as a tunable laser dye.

The basic unit of the PM dye is pyrrole which is condensed with suitable acid chloride or aldehyde to form dipyrromethene. The complexation of a dipyrromethene unit to a boron trifluoride salt lead to the formation of the dipyrrometheneboron difluoride structure, which can be considered as being an example of a "rigidified" monomethine cyanine dye. The greatly restricted flexibility leads to unusually high fluorescence yields from the dipyrromethene-boron framework. Conjugation of the p-electrons runs along the organic backbone and can be extended by attachment of suitable groups onto the periphery or to one or both pyrrole fragments. 

2. Brief description of Pyrromethene 567 and Pyrromethene 597

Process development of widely used, highly fluorescent and photo-chemically stable laser dyes - Pyrromethene 567 (PM567) [7] and Pyrromethene 597 (PM597) [7] belongs to PM dye family, in high purity (>99%) and good yield, are proposed for technology transfer. The functional use of this relatively recent fluorescent molecule, substituting Xanthene class dyes, will increase in next decades.
Researchers and technologists have been using these relatively recent laser dyes as gain media in dye lasers which are operated at high-repetition-rate (>10 KHz), high average power, as well as, low-repetition-rate (10-100 Hz), high peak intensity (several MW/cm2). These fluorescent molecules and their functionalized derivatives have great potential to use as chemosensors, biolabeling and in photodynamic therapy for effective generation of singlet oxygen. A few shortcomings of the commercially available laser dye sample are also addressed in order to improve their performance characteristics such as purity, solubility, quantum yield of fluorescence, lasing efficiency and photochemical stability.

3. Salient Features

• Highly fluorescent dyes.
• Very high extinction coefficients.
• High lasing efficiency.
• Wide spectral range (550-610 nm) for dye laser application.
• Good solubility in common organic solvents (EtOH, MeOH etc.)
• Dye lasers may be pumped by both second harmonic of Nd-YAG (at 532 nm) and green output of CVLs (at 511 nm) or DPSSGLs (at 532 nm).
• Highly Cost effective compared to imported products.

4. Specific uses of the dyes PM567 and PM597

This highly fluorescent Pyrromethene dye is widely used as gain medium in the constructed high average power, narrow line width dye lasers. In addition, many dye laser labs, biological and chemical labs in various research institutes in India have been using this costly fluorescent dye through import. This dye is dissolved in ethanol, methanol or n-heptane solvent and used in high power dye lasers as gain medium to obtain efficient and sustainable dye laser action in the visible spectral range 550-610 nm. These dye lasers may be pumped by second harmonic of Nd-YAG or diode pumped solid state laser (at 532 nm) or green output (at 511 nm) of Copper Vapour lasers (CVL). The Perennial problem  of rapid photochemical degradation of these dyes in liquid dye lasers are substantially reduced using additive DABCO and/or purging of N2 in alcohol or n-heptane solvent. These fluorescent molecules and  their functionalized derivatives have great potential to use as cation/anion chemosensors, biolebelling and in photodynamic therapy for effective generation of singlet oxygen.

5. Facilities and materials required for commercial production

5.1 Infrastructure: Small room (approximately 10-15 sq. Metre) with organic synthesis facility (Fumehood, working table, N2/Ar gas supply, TLC plates, standard glass apparatus, lab coat, safety glass etc.) and laboratory equipments (NMR, Rota evaporator, weighing balance etc.).

5.2 Manpower required: One Technician with Organic Chemistry background.
5.3 Chemicals and solvents: The Chemicals and solvents that are required for the synthesis are available with local chemical and laboratory equipments suppliers.

6. Quality of the product developed

The comparative laser performances of the developed products were evaluated with the imported product and shown below, which establishes superior quality of the locally developed dye sample. 

7.1 PM567:
Test sample         : PM567 synthesized at BARC.
Reference sample: PM567, M/S. Exciton, USA.
Solvent                : Ethyl alcohol.

Table 1: Comparative laser characteristics of commercial and synthesized PM 567 dye

7.2 PM597:
Test sample         : PM597 synthesized at BARC
Reference sample: PM597, M/S. Exciton, USA.
Solvent                : Ethyl alcohol.

Table 2. Comparative laser characteristics of commercial and synthesized PM 597 dye.

References:

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3. (a) Pavlopoulos, T. G.; Boyer, J. H.; Thangaraj, K.; Sathyamoorthi, G.; Shah, M. P.; Soong, M. L. Appl. Opt. 1992, 31, 7089-7094. (b) Guggenheimer, S. C.; Boyer, J. H.; Thangaraj, K.; Shah, M. P.; Soong, M. L.; Pavlopoulos, T. G. Appl. Opt. 1993, 32, 3942-3943. (c) Duchowicz, R.; Scaffardi, L. B.; Costela, A.; García-Moreno, I.; Sastre, R.; Acuña, A. U. Appl. Opt. 2003, 42, 1029-1035. (d) Ray, A. K.; Kundu, S.; Sasikumar, S.; Rao, C. S.; Mula, S.; Sinha, S.; Dasgupta, K. Appl. Phys. B 2007, 87, 483-488. (e) Mula, S.; Ray, A. K.; Banerjee, M.; Chaudhuri, T.; Dasgupta, K.; Chattopadhyay, S. J. Org. Chem. 2008, 73, 2146-2154. (f) Jagtap, K. K.; Shivran, N.; Mula, S.; Naik, D. B.; Sarkar, S. K.; Mukherjee, T.; Maity, D. K.; Ray, A. K. Chem. Eur. J. 2013, 19, 702-708. (g) Duran-Sampedro, G.; Esnal, I.; Agarrabeitia, A. R.; Prieto, J. B.; Cerdán, L.; García-Moreno, I.; Costela, A.;  Arbeloa, I. L.; Ortiz, M. J. Chem. Eur. J. 2014, 20, 2646-2653.
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5. (a)http://www.google.com/patents/US5189029 
   (b)http://www.google.co.in/patents/US4916711