Femtosecond linear dichroism of DNA-intercalating chromophores: solvation and charge separation dynamics of [Ru(phen)2dppz]2+ systems.

The DNA-intercalating chromophore [Ru(phen)(2)dppz](2+) has unique photophysical properties, the most striking of which is the "light-switch" characteristic when binding to DNA. As a dimer, it acts as a molecular staple for DNA, exhibiting a remarkable double-intercalating topology. Herein, we report femtosecond dynamics of the monomeric and the covalently linked dimeric chromophores, both free in aqueous solution and complexed with DNA. Transient absorption and linear dichroism show the electronic relaxation to the lowest metal-to-ligand charge-transfer (CT) state, and subpicosecond kinetics have been observed for this chromophore for what is, to our knowledge, the first time. We observe two distinct relaxation processes in aqueous solution with time constants of 700 fs and 4 ps. Interestingly, these two time constants are very similar to those observed for the reorientational modes of bulk water. The 700-fs process involves a major dichroism change. We relate these observations to the change in charge distribution and to the time scales involved in solvation of the CT state. Slower processes, with lifetimes of approximately 7 and 37 ps, were observed for both monomer and dimer when bound to DNA. Such a difference can be ascribed to the change of the structural and electronic relaxation experienced in the DNA intercalation pocket. Finally, the recombination lifetime of the final metal-to-ligand CT state to the ground state, which is a key in the light-switch process, is found in aqueous solution to be sensitive to structural modification, ranging from 260 ps for [Ru(phen)(2)dppz](2+) and 360 ps for the monomer chromophore derivative to 2.0 ns for the dimer. This large change reflects the direct role of solvation in the light-switch process.

Consequences of weight cycling in obese spontaneously hypertensive rats.

We mimicked human weight cycling in the obese spontaneously hypertensive rat (SHROB) model of genetic obesity. A 12-day very low calorie diet (VLCD; 16.7% of baseline calories) was alternated with 4-6 wk of ad libitum chow refeeding for three cycles. Control SHROB ate chow ad libitum. VLCD induced rapid weight loss, but during refeeding all the lost weight was regained. Final body weight was higher in cycled rats than in ad libitum controls (149 +/- 5 vs. 117 +/- 7% of initial baseline). Less weight was lost as a percent of starting body weight during each successive VLCD, which could not be explained by aging. At death, retroperitoneal fat pads were heavier in cycled SHROB than in ad libitum controls (62 +/- 3 vs. 44 +/- 4 g). During the first 2 days after each VLCD, cycled rats overate significantly relative to ad libitum controls (88 +/- 2 vs. 78 +/- 3 kcal/day), but cumulative food intake throughout the duration of the experiment did not differ (11.4 +/- 0.6 vs. 11.7 +/- 0.1 Mcal). Compared with ad libitum-fed rats, food efficiency (g body wt gain/kcal) was increased during each refeeding period. Weight cycling elevated blood pressure above the initial baseline throughout refeeding. Refeeding hypertension was abolished by ganglionic blockade with chlorisondamine. Thus weight cycling in SHROB exacerbates obesity, metabolic efficiency, abdominal fat accumulation, sympathetic activity, and hypertension.

Refeeding hypertension in obese spontaneously hypertensive rats.

Very-low-calorie diets lower blood pressure acutely in obese humans and rats. However, refeeding after dietary restriction produces mild hypertension in rats. Refeeding hypertension was characterized in genetically obese spontaneously hypertensive rats (obese SHR, Koletsky rat), a model of genetic obesity and hypertension. Obese SHR were fed a restricted diet (Optifast) for 12 days, refed ad libitum for 28 days, dieted again for 12 days, and then refed 4 days and killed. Control obese SHR and lean SHR littermates were fed ad libitum continuously. Dietary restriction led to rapid weight loss followed by prompt regain to baseline weight after return to unrestricted food intake. Heart rate fell with institution of the low-calorie diet and returned to baseline on refeeding. Blood pressure became elevated during refeeding in dieted obese SHR relative to ad libitum fed obese SHR controls. The fall in blood pressure after ganglionic blockade with chlorisondamine was exaggerated in refed obese SHR, and cardiac beta-adrenergic receptors were downregulated. Both of these findings imply increased sympathetic tone. The left ventricular wall was thicker in the refed obese SHR than in the ad libitum fed obese SHR. Shorter cycles of weight loss and regain in lean SHR led to transient increases in blood pressure and heart rate. Cycles of dietary restriction and refeeding in obese SHR elicit sustained blood pressure elevation via sympathetic activation and exacerbate cardiac hypertrophy. Drastic fluctuations in nutrient intake may not be advantageous in hypertension.