The brain is not only immunologically active of its own accord, but also has complex peripheral immune interactions. Given the central role of cytokines in neuroimmmunoendocrine processes, it is hypothesized that these molecules influence cognition via diverse mechanisms. Peripheral cytokines penetrate the blood-brain barrier directly via active transport mechanisms or indirectly via vagal nerve stimulation. Peripheral administration of certain cytokines as biological response modifiers produces adverse cognitive effects in animals and humans. There is abundant evidence that inflammatory mechanisms within the central nervous system (CNS) contribute to cognitive impairment via cytokine-mediated interactions between neurons and glial cells. Cytokines mediate cellular mechanisms subserving cognition (e.g., cholinergic and dopaminergic pathways) and can modulate neuronal and glial cell function to facilitate neuronal regeneration or neurodegeneration. As such, there is a growing appreciation of the role of cytokine-mediated inflammatory processes in neurodegenerative diseases such as Alzheimer's disease and vascular dementia. Consistent with their involvement as mediators of bidirectional communication between the CNS and the peripheral immune system, cytokines play a key role in the hypothalamic-pituitary-adrenal axis activation seen in stress and depression. In addition, complex cognitive systems such as those that underlie religious beliefs, can modulate the effects of stress on the immune system. Indirect means by which peripheral or central cytokine dysregulation could affect cognition include impaired sleep regulation, micronutrient deficiency induced by appetite suppression, and an array of endocrine interactions. Given the multiple levels at which cytokines are capable of influencing cognition it is plausible that peripheral cytokine dysregulation with advancing age interacts with cognitive aging.

The photophysics of a butadiyne-linked porphyrin dimer has been investigated by spectroscopy and quantum mechanical calculations. Primarily, the influence of conformation on the ground and first singlet excited states was studied, and two spectroscopically distinct limiting cases were identified. Experiments show that the twisted and planar conformers are separate spectroscopic species that can be selectively excited and have unique absorption and emission spectra. Calculated ground-state spectra compare well with experimental spectra of the two species. A spectrum of the planar conformer was obtained by the addition of a dipyridyl pyrrole ligand, which forms a 1:1 complex with the dimer and thus forces it to stay planar. The absorption spectrum of the twisted conformer could be deduced from the excitation spectrum of its emission. The interpretation of the ground-state spectrum of the free noncomplexed dimer is that it represents an average of a broad distribution of conformations. Calculations support this conclusion by indicating that the barrier for rotation is relatively small in the ground state (0.7 kcal/mol). Studies of the temperature dependence of the fluorescence spectrum of the dimer indicate a mother-daughter relationship between the twisted and planar conformations in the excited state, where the former has approximately 3.9 kcal/mol higher energy. Furthermore, time-correlated single-photon counting experiments also suggest that the twisted population adopts a planar configuration in the first singlet excited state with a rate constant of k rot ) 8.8 × 10 9 s -1 in 2-MTHF at room temperature. The temperature dependence of the fluorescence lifetimes indicated that an activation energy barrier of approximately 2 kcal/mol, in part related to solvent viscosity, is associated with this rate constant.

Electron transfer over long distances is important for many future applications in molecular electronics and solar energy harvesting. In these contexts, it is of great interest to find molecular systems that are able to efficiently mediate electrons in a controlled manner over nanometer distances, that is, structures that function as molecular wires. Here we investigate a series of butadiyne-linked porphyrin oligomers with ferrocene and fullerene (C60) terminals separated by one, two, or four porphyrin units (Pn, n = 1, 2, or 4). When the porphyrin oligomer bridges are photoexcited, long-range charge separated states are formed through a series of electron-transfer steps and the rates of photoinduced charge separation and charge recombination in these systems were elucidated using time-resolved absorption and emission measurements. The rates of long-range charge recombination, through these conjugated porphyrin oligomers, are remarkably fast (kCR2 = 15 - 1.3 x 108 s-1) and exhibit very weak distance dependence, particularly comparing the systems with n = 2 and n = 4. The observation that the porphyrin tetramer mediates fast long-range charge transfer, over 65 A, is significant for the application of these structures as molecular wires.