RESUMEN
In natural photosynthesis, the protein backbone directs and positions primary and secondary electron donor and acceptor moieties in the reaction center to control the yield and kinetics of the sequential electron transfer reactions that transform light energy into chemical potential. Organization of the active cofactors is mainly driven by noncovalent interactions between the protein scaffold and the chromophores. Based on the natural system blueprint, several research efforts have investigated π-π stacking, ionic interactions as well as formation of hydrogen and coordinative bonds as noncovalent organizing principles for the assembly of electron donors and acceptors in artificial reaction centers. Introduction of supramolecular concepts into the organization of electron donor-acceptor in artificial photosynthetic models raises the possibility of applying template-directed synthesis techniques to assemble interlocked systems in which the photo-redox components are mechanically rather than covalently linked. Rotaxanes and catenanes are the leading examples of interlocked molecules, whose recent developments in synthetic chemistry have allowed their efficient preparation. Introduction of mechanical bonds into electron donor-acceptor systems allows the study of the interlocked components' submolecular motions and conformational changes, which are triggered by external stimuli, on the thermodynamic and kinetic parameters of photoinduced processes in artificial reaction centers. This Tutorial discusses our efforts in the synthesis and photophysical investigation of rotaxanes and catenanes decorated with peripheral electron donors and [60]fullerene as the acceptor. The assembly of our rotaxanes and catenanes is based on the classic 1,10-phenanthroline-copper(i) metal template strategy in conjunction with the virtues of the Cu(i)-catalyzed-1,3-dipolar cycloaddition of azides and alkynes (the CuAAC or "click" reaction) as the protocol for the final macrocyclization or stoppering reactions of the entwined precursors. Time-resolved emission and transient absorption experiments revealed that upon excitation, our multichromophoric rotaxanes and catenanes undergo a cascade of sequential energy and electron transfer reactions that ultimately yield charge separated states with lifetimes as long as 61 microseconds, thereby mimicking the functions of the natural systems. The importance of the Cu(i) ion (used to assemble the interlocked molecules) as an electronic relay in the photoinduced processes is also highlighted. The results of this research demonstrate the importance of the distinct molecular conformations adopted by rotaxanes and catenanes in the electron transfer dynamics and illustrate the versatility of interlocked molecules as scaffolds for the organization of donor-acceptor moieties in the design of artificial photosynthetic reaction centers.
RESUMEN
OBJECTIVE: The aim of this study was to investigate pre-90Y lung shunt fraction (LSF) as a prognostic factor for overall survival (OS) in 90Y (resin/glass) planning 99mTc-MAA hepatopulmonary shunt studies for primary (hepatocellular carcinoma [HCC], intrahepatic cholangiocarcinoma) and metastatic liver tumors. METHODS: A total of 366 consecutive patients with primary and metastatic liver tumors underwent pre-90Y shunt study and 90Y radioembolization (mean age, 59.2 years; 55% were male). MAA (mean activity, 3.65 mCi) was administered via the proper hepatic artery. Shunted lung activity was obtained by planar scintigraphy. Median LSF values for primary tumors and metastases were compared with OS from first 90Y therapy via Kaplan-Meier estimation and log-rank test. Correlations between LSF and tumor involvement on baseline cross-sectional imaging were analyzed using Pearson coefficient (r). Patients with LSF of greater than 20% were deemed unsuitable for 90Y. RESULTS: The study included 79 (21.5%) colorectal, 73 (20%) neuroendocrine, 70 (19.1%) HCC, 40 (10.9%) intrahepatic cholangiocarcinoma, 40 (10.9%) melanoma, 20 (5.5%) breast, and 44 (12%) other tumors including lung and pancreatic cancers. Lung shunt fractions of less than 10% and 10% to 20% were observed in 235 patients (64.2%) and 131 patients (35.8%), respectively. Median LSFs were as follows: colorectal cancer (7.60%), neuroendocrine tumor (7.01%), HCC (11.47%), cholangiocarcinoma (7.00%), melanoma (6.00%), breast cancer (7.00%), and others, including lung and pancreatic metastases to the liver (8.36%). The HCC median LSF was significantly higher than that in non-HCC tumors, 11.47% versus 7.10% (P < 0.001). High LSF (≥ 10%) in HCC correlated with poorer survival from first 90Y compared with low LSF (<10%; 4.5 vs 16.4 months, P = 0.003). Similarly, for metastatic disease, high LSF demonstrated significantly poorer survival compared with low LSF in colorectal liver metastases (13.5 vs 7.0 months, P = 0.013), neuroendocrine liver metastases (33.0 vs 9.1 months, P < 0.001), and melanoma liver metastases (12.0 vs 5.0 months, P = 0.03). No correlation between tumor burden on cross-sectional imaging and LSF was observed (r = 0.35). CONCLUSIONS: In patients who are candidates for 90Y therapy, higher LSF is a poor prognostic factor for OS in HCC and metastatic liver tumors.