math5 is a murine orthologue of atonal, a bHLH proneural gene essential for the formation of photoreceptors and chordotonal organs in Drosophila. The expression of math5 coincides with the onset of retinal ganglion cell (RGC) differentiation. Targeted deletion of math5 blocks the initial differentiation of 80% of RGCs and results in an increase in differentiated amacrine cells. Furthermore, the absence of math5 abolishes the retinal expression of brn-3b and the formation of virtually all brn-3b-expressing RGCs. These results imply that math5 is a proneural gene essential for RGC differentiation and that math5 acts upstream to activate brn-3b-dependent differentiation processes in RGCs. The mammalian retina is the peripheral portion of the visual system containing six major neuronal cell types and one glial cell type organized in a laminar structure. The visual information process in the retina follows a general pathway from photoreceptors to bipolar cells to retinal ganglion cells (RGCs). Horizontal cells and amacrine cells act to mediate lateral interactions among photoreceptors, bipolar cells, and RGCs. The latter serve as the sole output neurons in the retina to send the visual information down the optic nerve to the rest of brain. Both birthdating experiments using 3 H-thymidine labeling and cell lineage analysis using retroviral and tracermediated approaches demonstrate that vertebrate retinal neurons are generated from common progenitors through sequential differentiation and ordered migration to form the laminar retinal structure (Cepko et al. 1996). Current models for retinal neuron differentiation suggest that the formation of a specific retinal neuron is determined by the intrinsic properties of the retinal progenitor and the extrinsic cues from the retinal environment (Cepko et al. 1996). Among the likely intrinsic factors, the basic helix-loop-helix (bHLH) class of proneural transcription factors appears to play an essential role in regulating the differentiation of retinal neurons (Cepko 1999). In Drosophila, expression of proneural genes of the achaete-scute complex (AS-C) and atonal (ato) in proneural clusters endow cells with neural competence (Jan and Jan 1993). Loss-of-function mutation of genes in AS-C causes the cells in the would-be proneural clusters to adopt epidermal fates rather than neuronal precursor fates. Conversely, gain-of-function mutations in the proneural genes leads to the ectopic formation of sensory neurons (Campuzano and Modolell 1992). The expression of ato is found in the optic furrow of the eye-antennal disc in addition to the ectodermal proneural clusters and sensory organ precursors, which give rise to the chordotonal organs. Deletion of ato causes the absence of the chordotonal organ and the lack of photoreceptors (Jarman et al. 1995), and the reduced expression of ato results in defects in axonal pathfinding of photoreceptors (White and Jarman 2000), suggesting that ato plays dual roles in determining neuronal potential and regulating specific neuronal differentiation...

Intermolecular electron transfer (ET) between the free phenothiazine donor (PH) and its cation radical (PH*+) proceeds via the [1:1] precursor complex (PH)(2)*+ which is transiently observed for the first time by its diagnostic (charge-resonance) absorption band in the near-IR region. Similar intervalence (optical) transitions are also observed in mixed-valence cation radicals with the generic representation: P(br)P*+, in which two phenothiazine redox centers are interlinked by p-phenylene, o-xylylene, and o-phenylene (br) bridges. Mulliken-Hush analysis of the intervalence (charge-resonance) bands afford reliable values of the electronic coupling element H(IV) based on the separation parameters for (P/P*+) centers estimated from some X-ray structures of the intermolecular (PH)(2)*+ and the intramolecular P(br)P*+ systems. The values of H(IV), together with the reorganization energies lambda derived from the intervalence transitions, yield activation barriers DeltaG(ET)() and first-order rate constants k(ET) for electron-transfer based on the Marcus-Hush (two-state) formalism. Such theoretically based values of the intrinsic barrier and ET rate constants agree with the experimental activation barrier (E(a)) and the self-exchange rate constant (k(SE)) independently determined by ESR line broadening measurements. This convergence validates the use of the two-state model to adequately evaluate the critical electronic coupling elements between (P/P*+) redox centers in both (a) intermolecular ET via the precursor complex and (b) intramolecular ET within bridged mixed-valence cation radicals. Important to intermolecular ET mechanism is the intervention of the strongly coupled precursor complex since it leads to electron-transfer rates of self-exchange that are 2 orders of magnitude faster (and activation barrier that is substantially lower) than otherwise predicted solely on the basis of Marcus reorganization energy.

X-ray crystallography identifies the aromatic donor group D = 2,5-dimethoxy-4-methylphenyl to be a suitable redox center for the construction of organic mixed-valence crystals owing to its large structural change attendant upon 1e oxidation to the cation-radical (D*(+)). The combination of cyclic voltammetry, dynamic ESR line broadening, and electronic (NIR) spectroscopy allows the intervalence electron transfer between the redox centers in the mixed-valence system D-br-D*(+) [where br can be an aliphatic trimethylene or an aromatic (poly)phenylene bridge] to be probed quantitatively. Independent measures of the electronic coupling matrix element (H) for D/D*(+) electron exchange via Mulliken-Hush theory accord with the X-ray crystallographic data-both sufficient to consistently identify the various D-br-D*(+) according to the Robin-Day classification. Thus, the directly coupled biaryl D-D*(+) is a completely delocalized cation in class III with the charge distributed equally over both redox centers. The trimethylene- and biphenylene-bridged cations D(CH(2))(3)D*(+) and D(ph)(2)D*(+) with highly localized charge distributions are prototypical class II systems involving moderately coupled redox centers with H approximately equal to 400 cm(-1). The borderline region between class II/III is occupied by the phenylene-bridged cation D(ph)D*(+); and the X-ray, CV, and NIR analyses yield ambivalent H values (which we believe to be) largely a result of an unusually asymmetric (20/80) charge distribution that is polarized between the D/D*(+) redox centers.

Intramolecular electron transfer in the organic mixed-valence cation radical D(ph) n D +• [where D ) 2,5dimethoxy-4-methylphenyl and (ph) n ) poly-p-phenylene] is systematically probed by the structural modification of the molecular conformation, separation distance, and electronic connectiVity of the (ph) n bridge. Cyclic voltammetry and dynamic ESR line broadening studies afford experimental measures of the energy gap (∆E ox ) and the electron-transfer kinetics (k ET ) for the D/D +• interaction in a series of methyl-substituted, (poly)phenylene, and bridged-modified ph-X-ph (where X ) CtC, CHdCH, O, and CH 2 CH 2 inserts or the (CH 3 ) 2 C tiedown) bridges that comprise the groups A-C donors in Chart 1. Theoretical electron-transfer rates are obtained by the application of the Creutz, Newton, and Sutin (CNS) superexchange model (for the calculation of the electron coupling matrix element H CNS ) to the diagnostic NIR absorptions that arise from the intramolecular bridge-to-redox center (i.e., br f D +• ) charge-transfer transitions. Comparison of the experimental and theoretical electron-transfer rates (k ET ) indicate that the CNS model is sufficient to provide a mechanistic basis for including conformation, distance and connectivity effects in the design of (poly)phenylene bridges for new organic mixed-valence systems. † Part of the special issue "Noboru Mataga Festschrift". Dedicated to Professor Noboru Mataga for his pioneering contributions to our understanding of (fast) electron-transfer processes.

Intervalence absorption bands appearing in the diagnostic near-IR region are consistently observed in the electronic spectra of mixed-valence systems containing a pair of aromatic redox centers (Ar •+ /Ar) that are connected by two basically different types of molecular bridges. The through-space pathway for intramolecular electron transfer is dictated by an o-xylylene bridge in the mixed-valence cation radical 3•+ with Ar = 2,5-dimethoxy-p-tolyl (T), in which conformational mobility allows the proximal syn disposition of planar T•+ /T redox centers. Four independent experimental probes indicate the large through-space electronic interaction between such cofacial Ar•+ /Ar redox centers from the measurements of (a) sizable potential splitting in the cyclic voltammogram, (b) quinonoidal distortion of T•+ /T centers by X-ray crystallography, (c) "doubling" of the ESR hyperfine splittings, and (d) a pronounced intervalence charge-resonance band. The through (br)-bond pathway for intramolecular electron transfer is enforced in the mixed-valence cation radical 2a•+ by the p-phenylene bridge which provides the structurally inflexible and linear connection between Ar•+ /Ar redox centers. The direct comparison of intramolecular rates of electron transfer (kET) between identical T•+ /T centers in 3•+ and 2a•+ indicates that through-space and through-bond mechanisms are equally effective, despite widely different separations between their redox centers. The same picture obtains for 3•+ and 2a•+ from theoretical computations of the first-order rate constants for intramolecular electron transfer from Marcus−Hush theory using the electronic coupling elements evaluated from the diagnostic intervalence (charge-transfer) transitions. Such a strong coherence between theory and experiment also applies to the mixed-valence cation radical 7•+ , in which the aromatic redox S center is sterically encumbered by annulation.