Bioconjugatable, PEGylated Hydroporphyrins for Photochemistry and Photomedicine. Narrow-Band, Red-Emitting Chlorins.
Chromophores that absorb and emit in the red spectral region (600-700 nm), are water soluble, and bear a bioconjugatable tether are relatively rare yet would fulfill many applications in photochemistry and photomedicine. Here, three molecular designs have been developed wherein stable synthetic chlorins - analogues of chlorophylls - have been tailored with PEG groups for use in aqueous solution. The designs differ with regard to order of the installation (pre/post-formation of the chlorin macrocycle) and position of the PEG groups. Six PEGylated synthetic chlorins (three free bases, three zinc chelates) have been prepared, of which four are equipped with a bioconjugatable (carboxylic acid) tether. The most effective design for aqueous solubilization entails facial encumbrance where PEG groups project above and below the plane of the hydrophobic disk-like chlorin macrocycle. The chlorins possess strong absorption at ~400 nm (B band) and in the red region (Qyband); regardless of wavelength of excitation, emission occurs in the red region. Excitation in the ~400 nm region thus provides an effective Stokes shift of >200 nm. The four bioconjugatable water-soluble chlorins exhibit Qyabsorption/emission in water at 613/614, 636/638, 698/700 and 706/710 nm. The spectral properties are essentially unchanged in DMF and water for the facially encumbered chlorins, which also exhibit narrow Qyabsorption and emission bands (full-width-at-half maximum of each <25 nm). The water-solubility was assessed by absorption spectroscopy over the concentration range ~0.4 μM - 0.4 mM. One chlorin was conjugated to a mouse polyclonal IgG antibody for use in flow cytometry with compensation beads for proof-of-principle. The conjugate displayed a sharp signal when excited by a violet laser (405 nm) with emission in the 620-660 nm range. Taken together, the designs described herein augur well for development of a set of spectrally distinct chlorins with relatively sharp bands in the red region.
Department of Chemistry, North Carolina State University, Raleigh, NC 27695-8204.
Mengran
M
Liu
Department of Chemistry, North Carolina State University, Raleigh, NC 27695-8204.
Chih-Yuan
CY
Chen
Department of Chemistry, Washington University, St. Louis, MO 63130-4889.
Amit Kumar
AK
Mandal
Department of Chemistry, North Carolina State University, Raleigh, NC 27695-8204.
Vanampally
V
Chandrashaker
NIRvana Sciences, Research Triangle Park, NC 27709-3169.
Rosemary B
RB
Evans-Storms
NIRvana Sciences, Research Triangle Park, NC 27709-3169.
J Bruce
JB
Pitner
Department of Chemistry, University of California, Riverside, CA 92521-0403.
David F
DF
Bocian
Department of Chemistry, Washington University, St. Louis, MO 63130-4889.
Dewey
D
Holten
Department of Chemistry, North Carolina State University, Raleigh, NC 27695-8204.
Jonathan S
JS
Lindsey