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Highly Non-Planar Dendritic Porphyrin for pH Sensing: Observation of Porphyrin Monocation

Thyagarajan, Sujatha; Leiding, Thom LU ; Peterson Årsköld, Sindra LU ; Cheprakov, Andrei V. and Vinogradov, Sergei A. (2010) In Inorganic Chemistry 49(21). p.9909-9920
Abstract
Metal-free porphyrin-dendrimers provide a convenient platform for the construction of membrane-impermeable ratiometric probes for pH measurements in compartmentalized biological systems. In all previously reported molecules, electrostatic stabilization (shielding) of the core porphyrin by peripheral negative charges (carboxylates) was required to shift the intrinsically low porphyrin protonation pK(a)'s into the physiological pH range (pH 6-8). However, binding of metal cations (e.g., K+, Na+, Ca2+, Mg2+) by the carboxylate groups on the dendrimer could affect the protonation behavior of such probes in biological environments. Here we present a clendritic pH nanoprobe based on a highly non-planar tetraaryltetracyclohexenoporphyrin... (More)
Metal-free porphyrin-dendrimers provide a convenient platform for the construction of membrane-impermeable ratiometric probes for pH measurements in compartmentalized biological systems. In all previously reported molecules, electrostatic stabilization (shielding) of the core porphyrin by peripheral negative charges (carboxylates) was required to shift the intrinsically low porphyrin protonation pK(a)'s into the physiological pH range (pH 6-8). However, binding of metal cations (e.g., K+, Na+, Ca2+, Mg2+) by the carboxylate groups on the dendrimer could affect the protonation behavior of such probes in biological environments. Here we present a clendritic pH nanoprobe based on a highly non-planar tetraaryltetracyclohexenoporphyrin (Ar4TCHP), whose intrinsic protonation pKa's are significantly higher than those of regular tetraarylporphyrins, thereby eliminating the need for electrostatic core shielding. The porphyrin was modified with eight Newkome-type dendrons and PEGylated at the periphery, rendering a neutral water-soluble probe (TCHpH), suitable for measurements in the physiological pH range. The protonation of TCHpH could be followed by absorption (e.g., epsilon(Soret)(dication)similar to 270,000 M-1 cm(-1)) or by fluorescence. Unlike most tetraarylporphyrins, TCHpH is protonated in two distinct steps (pK(a)'s 7.8 and 6.0). In the region between the pK(a)'s, an intermediate species with a well-defined spectroscopic signature, presumably a TCHpH monocation, could be observed in the mixture. The performance of TCHpH was evaluated by pH gradient measurements in large unilamellar vesicles. The probe was retained inside the vesicles and did not pass through and/or interact with vesicle membranes, proving useful for quantification of proton transport across phospholipid bilayers. To interpret the protonation behavior of TCHpH we developed a model relating structural changes on the porphyrin macrocycle upon protonation to its basicity. The model was validated by density functional theory (DFT) calculations performed on a planar and non-planar porphyrin, making it possible to rationalize higher protonation pK(a)'s of non-planar porphyrins as well as the easier observation of their monocations. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Inorganic Chemistry
volume
49
issue
21
pages
9909 - 9920
publisher
The American Chemical Society
external identifiers
  • wos:000283279800026
  • scopus:78049280722
ISSN
1520-510X
DOI
10.1021/ic100968p
language
English
LU publication?
yes
id
610d69ad-40ea-44a0-9ceb-e612a1de5268 (old id 1720498)
date added to LUP
2010-12-09 13:08:42
date last changed
2018-06-10 03:20:06
@article{610d69ad-40ea-44a0-9ceb-e612a1de5268,
  abstract     = {Metal-free porphyrin-dendrimers provide a convenient platform for the construction of membrane-impermeable ratiometric probes for pH measurements in compartmentalized biological systems. In all previously reported molecules, electrostatic stabilization (shielding) of the core porphyrin by peripheral negative charges (carboxylates) was required to shift the intrinsically low porphyrin protonation pK(a)'s into the physiological pH range (pH 6-8). However, binding of metal cations (e.g., K+, Na+, Ca2+, Mg2+) by the carboxylate groups on the dendrimer could affect the protonation behavior of such probes in biological environments. Here we present a clendritic pH nanoprobe based on a highly non-planar tetraaryltetracyclohexenoporphyrin (Ar4TCHP), whose intrinsic protonation pKa's are significantly higher than those of regular tetraarylporphyrins, thereby eliminating the need for electrostatic core shielding. The porphyrin was modified with eight Newkome-type dendrons and PEGylated at the periphery, rendering a neutral water-soluble probe (TCHpH), suitable for measurements in the physiological pH range. The protonation of TCHpH could be followed by absorption (e.g., epsilon(Soret)(dication)similar to 270,000 M-1 cm(-1)) or by fluorescence. Unlike most tetraarylporphyrins, TCHpH is protonated in two distinct steps (pK(a)'s 7.8 and 6.0). In the region between the pK(a)'s, an intermediate species with a well-defined spectroscopic signature, presumably a TCHpH monocation, could be observed in the mixture. The performance of TCHpH was evaluated by pH gradient measurements in large unilamellar vesicles. The probe was retained inside the vesicles and did not pass through and/or interact with vesicle membranes, proving useful for quantification of proton transport across phospholipid bilayers. To interpret the protonation behavior of TCHpH we developed a model relating structural changes on the porphyrin macrocycle upon protonation to its basicity. The model was validated by density functional theory (DFT) calculations performed on a planar and non-planar porphyrin, making it possible to rationalize higher protonation pK(a)'s of non-planar porphyrins as well as the easier observation of their monocations.},
  author       = {Thyagarajan, Sujatha and Leiding, Thom and Peterson Årsköld, Sindra and Cheprakov, Andrei V. and Vinogradov, Sergei A.},
  issn         = {1520-510X},
  language     = {eng},
  number       = {21},
  pages        = {9909--9920},
  publisher    = {The American Chemical Society},
  series       = {Inorganic Chemistry},
  title        = {Highly Non-Planar Dendritic Porphyrin for pH Sensing: Observation of Porphyrin Monocation},
  url          = {http://dx.doi.org/10.1021/ic100968p},
  volume       = {49},
  year         = {2010},
}