How the Donor/Acceptor Spin States Affect the Electronic Couplings in Molecular Charge-Transfer Processes?

The electronic coupling matrix element HAB is an essential ingredient of most electron-transfer theories. HAB depends on the overlap between donor and acceptor wave functions and is affected by the involved states' spin. We classify the spin-state effects into three categories: orbital occupation, spin-dependent electron density, and density delocalization. The orbital occupancy reflects the diverse chemical nature and reactivity of the spin states of interest. The effect of spin-dependent density is related to a more compact electron density cloud at lower spin states due to decreased exchange interactions between electrons. Density delocalization is strongly connected with the covalency concept that increases the spatial extent of the diabatic state's electron density in specific directions. We illustrate these effects with high-level ab initio calculations on model direct donor-acceptor systems relevant to metal oxide materials and biological electron transfer. Obtained results can be used to benchmark existing methods for HAB calculations in complicated cases such as spin-crossover materials or antiferromagnetically coupled systems.

NMR-spectroscopic and solid-state investigations of cometal-free asymmetric conjugate addition: a dinuclear paracyclophaneimine zinc methyl complex.

We present herein the first indications for dimeric structures in cometal-free asymmetric conjugate addition reactions of dialkylzinc reagents with aldehydes. These are revealed by nonlinear effect (NLE) studies. A monomer-dimer equilibrium can be assumed which explains the increase of the ee value in the product over time. Also, DOSY NMR spectroscopic measurements indicate the existence of the catalyst as [LZnEt](n) complexes in solution. Additionally, the first X-ray structure of a zinc complex with a [2.2]paracyclophane ligand was determined. The structures of the zinc complexes are supported by DFT calculations of monomeric and dimeric species.

Feasibility of high-dose three-dimensional radiation therapy in the treatment of localised non-small-cell lung cancer.

PURPOSE: Chemoradiotherapy is the standard treatment of inoperable and/or non-resectable IIIA/B non-small-cell lung cancer (NSCLC). Aware of the necessity to increase local control in locally advanced NSCLC, we analyzed the feasibility of high-dose three-dimensional conformal radiation therapy (3D-CRT) in the treatment of localised NSCLC. PATIENTS AND METHODS: We undertook a retrospective analysis of consecutive patients with non-resectable NSCLC treated with high-dose (74Gy) standard-fractionation 3D-CRT, with particular attention to the relationship between lung and heart radiation-induced toxicities. RESULTS: Fifty patients (41 males, 9 females) were included. A total of 35 (70%) patients received the planned total dose of 74Gy. Patients irradiated to inferior doses interrupted the treatment because of limiting toxicities. Induction and concurrent chemotherapy was delivered to 39 (78%) and 14 (28%) patients, respectively. Eight (16%) patients experienced grade 3-4 acute lung toxicity, all of them having a history of pulmonary disease, a FEV1 below 1.6 L, and a lung V(20) of at least 25%. Three (6%) patients were deemed to experience radiation-induced cardiac toxicity. CONCLUSIONS: This study assesses the feasibility of delivering a total dose of 74 Gy combined with chemotherapy in locally advanced NSCLC. High lung and heart V(20) increases the risk of radiation-induced lung and cardiac toxicity, the later being highly difficult to precisely assess, as late deaths are rarely documented, and responsibility of the treatment might be often underestimated. The precise evaluation of cardiac condition may be helpful to spare fragile patients from potentially toxic effects of high-dose radiation, especially in controlled trials.

[Dosimetric impact of breath-hold in the treatment of hepatocellular carcinoma by conformal radiation therapy]. / Impact dosimétrique du blocage respiratoire dans le traitement du carcinome hépatocellulaire par irradiation de conformation.

OBJECTIVE: To evaluate the dosimetric impact of breath-hold during radiotherapy of hepatocellular carcinoma (HCC) and to determinate the optimal respiratory phase for treatment (exhale or inhale). PATIENTS AND METHODS: Two CT scans were performed in inhale and in exhale in 20 patients with HCC. The GTV was delineated slice by slice on the inspiration breath hold acquisition (GTV(insp)) and on the expiration breath hold acquisition (GTV(exp)). The superposition of two GTV allowed to obtain the global GTV (free respiration). PTV was defined by adding a margin of 1cm around each GTV. The liver, the duodenum, the two kidneys, the stomach and the spinal cord were delineated on each acquisition as organs at risk (OAR). Three dosimetric plans were created on inspiration, expiration and on global PTV. RESULTS: The mean reduction in the volume of PTV with conformal radiation therapy (3D-CRT) in the hold-breath group compared to the free respiration group was of 33.5+/-11.9%. The average difference of V50%, V20, V30, V40 and V50 were around 4% in favor of the breath hold. The average value of NTCP was 8.9% in free respiration, 4.5% in expiration and 3.2% in inspiration. Further improvement in the OARs dosimetric parameters for the breath hold was observed. CONCLUSION: Compared to the conformal radiotherapy with free respiration, the breath-hold allows reducing the volume of the PTV and the doses to the healthy liver and organs at risk. The use of this modality during different radiotherapy techniques (3D-CRT, IMRT and stereotactic) may be recommended. No difference in dosimetric value has been observed between the breath hold in expiratory and inspiratory phases.

[Irradiation of hepatocellular carcinoma: impact of breathing on motions and variations of volume of the tumor, liver and upper abdominal organs]. / L'irradiation des carcinomes hépatocellulaires: impact de la respiration sur les mouvements et variations de volume de la tumeur, du foie et des organes intra-abdominaux.

PURPOSE: To evaluate the amplitude of motion and the variations of volume of the tumor, the liver and upper abdominal organs induced by breathing during the irradiation of hepatocellular carcinoma (HCC). MATERIAL AND METHODS: Two scanners were performed in inhale and in exhale not forced in 20 patients with a HCC. The liver (left/right lobes), the tumor, the duodenum, the two kidneys and the pancreas were delineated on each acquisition. The superposition of the two spirals made it possible to measure the displacements and variations of volume of these structures in the craniocaudal (CC), lateral (Lat), and anteroposterior (AP) directions. RESULTS: The mean displacement of the tumour in CC, Lat and AP was of 19.7+/-8.3 mm, 4.5+/-2.3 mm, and 8.9+/-6.5 mm. The greatest amplitude of movement was obtained in CC for the right and left hepatic lobes (19+/-6.5 mm, 10+/-5.6 mm), the duodenum(12.6+/-6.4 mm), the kidneys right and left (15.5+/-6.1 mm, 16.2+/-10 mm) and the pancreas (13.2+/-6 mm). No significant variation of volume was observed for these organs. CONCLUSION: The movements of the tumour, the liver and the abdominal organs, induced by breathing are significant. The respiratory gating appears essential in particular with the development of new techniques of irradiation such as the intensity-modulated radiotherapy (IMRT) or the stereotactic body radiation therapy (SBRT).

[Tolerance and efficacy of conformal radiotherapy for hepatocellular carcinoma in cirrhotic patients. Results of the French RTF1 phase II trial]. / Tolérance et efficacité de la radiothérapie de conformation en cas de carcinome hépatocellulaire chez le patient cirrhotique. Résultats de l'essai de phase II RTF1.

PURPOSE: While some patients presenting with hepatocellular carcinoma (HCC) benefit from curative therapies (transplantation, surgery, percutaneous ablation), others are only candidates for palliative options such as chemoembolization or symptomatic care. Although conventional external-beam radiotherapy of the liver is regarded as little efficient and potentially toxic in cirrhotic patients, 3-dimensional conformal radiotherapy (CRT), by decreasing the amount of normal liver included in the radiation portal, allows dose escalation to occur without increasing the risk of radiation-induced hepatitis. This trial was designed to assess the efficacy and tolerance of CRT for small-size HCC in cirrhotic patients. PATIENTS AND METHODS: Prospective phase II trial including stage A/B cirrhotic patients with small-size HCC not suitable for curative treatments; CRT consisted in a standard fractionation radiation, with a total dose of 66 Gy. RESULTS: Twenty-seven patients were included, 15 of whom had previously been treated for HCC; mean age was 68. Among the 23 assessable patients, 18 (78%) presented with complete response, 3 (13%) with partial response, and 2 with no response. Acute complications occurred in 24 patients, and were mainly acceptable (grade 1/2: 22 patients, grade 3/4: 11 patients, 4 (15%) of whom had clinical and/or hematological toxicities). Only 2 (9%) grade 3/4 clinical and/or hematological late toxicities are reported. CONCLUSION: CRT is a non-invasive curative technique highly suitable for small-size HCC in cirrhotic patients; further investigations are needed to compare it to the other available treatments, and to integrate it into the curative therapeutic algorithm of HCC.

[Chemoradiation for pancreatic adenocarcinoma]. / Chimioradiothérapie des adénocarcinomes pancréatiques.

Surgery remains the cornerstone treatment for pancreatic adenocarcinoma. However, 5% to 20% of tumors only are regarded as resectable, and, among them, only few benefit from an histological complete resection, major survival parameter. These data explain the overall poor prognosis of this disease, with a respectively 20% and 5% 1- and 5-year survival rates. These results justify an adjuvant or neoadjuvant therapeutic approach, mainly based on concurrent chemoradiation, with and without surgery. This paper reviews the different therapeutic approaches of non metastatic pancreatic adenocarcinoma.