We have synthesized and fully characterized three novel, yet closely related, heterocyclically meso-substituted (BODIPY) fluorophores 4,4-difluoro-8-(C(4)H(3)X)-4-bora-3a,4a-diaza-s-indacene (X = O, 2-/3-furyl (7/10); Se, 2-selenenyl (9)) through the use of 2-D NMR (COSY, HSQC, and HMBC), single crystal X-ray diffraction, mass spectrometry, elemental analysis, UV-vis spectroscopy, and fluorescent decay lifetimes, for comparison to the previously reported thienyl species (X = S, 2-/3-thienyl (8/11)). Specifically, 7-11 differ formally by chalcogen (O, S, or Se) or chalcogen placement. Solid state comparisons reveal major effects stemming from subtle structural differences which allows for insights into fluorescent crystal engineering. For the 2-heteroatom substitution, an increase in molecular weight (7 < 8 < 9) correlates with an increasing unit cell-volume, a greater orthogonality for the C(4)H(3)X group, and a lower value for Phi(F). Solution and density functional theory (DFT) results reveal interesting platforms for potential in fluorescent studies for neurology. 2-Heterocyclic species show larger lambda(abs,max/em,max) values relative to 3-heterocyclic ones, based on electron withdrawing effects. 10 has the greatest Phi(F) value herein (0.25, toluene). Fluorescence lifetimes were found to be 2.60 (7), 0.74 (8), 0.27 (9), 4.26 (10), and 1.86 ns (11); lambda(em,max) decay was studied for 8. Heterocyclic differences give rise to somewhat different pyrrolic NMR spectroscopic shifts as well. These compounds resist decomposition as seen from titrations with H(2)O(2), and uniformly undergo lambda(abs,max) red-shifting and lowered Phi(F) values as they become brominated with Br(2).