A first approach toward understanding the targeted design of molecular photoacoustic contrast agents (MPACs) is presented. Optical and photoacoustic Z-scan spectroscopy was used to identify how nonlinear (excited-state) absorption contributes to enhancing the photoacoustic emission of the curcuminBF2 and bis-styryl (MeOPh)2BODIPY dyes relative to Cy3.

An archetypal study is presented to correlate both the optical and the photoacoustic (PA) properties for a diverse selection of dyes whose structural properties range across organic and inorganic, symmetric and asymmetric, and neutral and cationic systems. Three distinct classes of molecular PA contrast agents have been identified and classified according to their optical-PA response as either (i) linear absorbers linear PA emitter, (ii) saturable absorbers weak PA emitter, or (iii) reverse saturable absorbers nonlinear PA emitter. The molecular characteristics instrumental in determining the nature of the dyes optical absorption properties, i.e., ground state molar extinction coefficient (εg), excited state molar extinction coefficient (εe), and excited state lifetime (τ), are discussed to aid in the interpretation of a molecule’s optical vs PA response. An excellent linear PA emitter is established in crystal violet, which exhibits the strongest possible PA signal under low laser fluence conditions in both PA Z-scan and tomography experiments. Ultimately, however, nonlinear reverse saturable absorber (RSA) materials are anticipated to be the most promising dye category for generation of an enhanced nonlinear PA response. Effective RSA behavior is expected for materials showing a high ratio of their excited state vs ground state absorption (εe/εg) while also possessing a long-lived excited state lifetime (τ) permitting sequential two-photon absorption. ZnTPP, C60, and methylene blue each show a nonlinear PA response which correlates well with their RSA optical behavior. Relative to the linear PA emission profile of crystal violet, a 3.8-fold enhancement is observed for the PA emission of ZnTPP at the highest laser fluence of 366 mJ cm–2. Similarly, C60 and methylene blue exhibit nonlinear enhancements of 2.15-fold and 1.38-fold, respectively. Finally, to investigate the practical pros and cons with respect to application of these dyes in PA imaging applications, a concentration dependence of their PA emission is presented at both low and high laser fluences, in addition to a complementary photoacoustic tomography study.

The synthesis and characterization of a series of donor-π-acceptor-π-donor (D-A-D) curcuminoid molecules is presented herein that incorporates π-extended aryl and electron-donating amino terminal functionalization. Computational evaluation shows these molecules possess quadrupolar character with the lowest energy transitions displaying high molar extinction coefficients with broad tunability through manipulation of terminal donating groups. Consistent with their quadrupolar nature, these molecules show varying degrees of solvatochromic behavior in both their absorption and emission spectra, which has been analyzed by Lippert-Mataga and Kamlet-Taft analysis. Photophysical and photoacoustic (PA) properties of these molecules have been investigated by the optical photoacoustic z-scan (OPAZ) method. Selected curcuminoid molecules display nonlinear behavior at a high laser fluence through excited state absorption that translates to the production of an enhanced photoacoustic emission. A relative comparison of "molar PA emission" is also presented with the crystal violet linear optical absorbing/linear PA emitting system being utilized as a standard reference material for OPAZ experiments. Furthermore, PA tomography experiments are presented to illustrate the enhanced PA contrast obtainable via an excited state absorption.

The nonlinear optical properties of a series of pyrrolic compounds consisting of BODIPY and aza-BODIPY systems are investigated using 532 nm nanosecond laser and the Z-scan technique. Results show that 3,5-distyryl extension of BODIPY to the red shifted MeO2BODIPY dye has a dramatic impact on its nonlinear absorption properties changing it from a saturable absorber to an efficient reverse saturable absorbing material with a nonlinear absorption coefficient of 4.64 × 10−10 m/W. When plotted on a concentration scale per mole of dye in solution MeO2BODIPY far outperforms the recognized zinc(II) phthalocyanine dye and is comparable to that of zinc(II) tetraphenylporphyrin.

The synthesis and characterization of a bis(2-dimethylaminothien-5-yl)curcumin boron difluoride chromophore is presented. Photophysical, electrochemical and computational investigations establish the properties of its absorption in the Vis-NIR spectral range relative to established curcumin dyes. Application of this thienyl curcumin dye as a photoacoustic contrast agent is investigated against the dicarbocyanine Cy5 dye in the 675-735 nm excitation range.