While simulated spectra were observed to be blue-shifted relative to experimental spectra, a high correlation (R 2 = 0.79) was observed between the corresponding absorption and emission maxima wavenumber values (Figure ). Motivated by the strong agreement between experimental and computational data, we modeled the absorbance and fluorescence emission spectra for 12 structures (5a-5l) containing a range of structural modifications (Supporting Information) and a general trend between fluorophore structure and spectral properties was established. Amongst a variety of structural variations, the effects of extension of conjugation on the emission were investigated through several benzannulated (5a -5d) modifications of the borindolizine scaffold (Figure ). Promisingly, isoquinioline-based borindolizine 5b was predicted to be a red-emissive fluorophore with a λmax,em of 646 nm (Figure ). In addition to spectral simulations, HOMO-LUMO energy gaps were calculated (B3LYP/6-31G**) for all simulated molecules. Lower-level and computationally inexpensive ground state DFT calculations offered compelling qualitative insights into the effects of scaffold changes on the frontier molecular orbitals of the heterocyclic scaffold (Figure ). From a frontier molecular orbital perspective, there are two strategies to reduce the HOMO-LUMO gap (HLG) -extension of conjugation (LUMO lowering effect) and changing the electron density of the conjugated system. The trend of increasing electron density from the boramidine (1, R = H) scaffold to the aryl borindolizine (3l) scaffold results in an increase in the HOMO energy level, resulting in a reduction in band gap energy from 4.46 eV to 3.81 eV. The extension of conjugation on the pyridine ring system leading to the isoquinolyl scaffold 5b leads to a LUMO lowering effect, reducing the band gap energy to 3.00 eV. Overall, the large change in band gap energy across the scope of scaffolds investigated (1.46 eV) is a strong indication of the dramatic changes in the intrinsic electronics of the fluorophoric scaffold. Guided by the above computational screen, isoquinoline precursor 2q was synthesized through reduction and subsequent Barluenga-Valdes cross-coupling of methyl isoquinoline-3-carboxylate 2p with p-tolylboronic acid (Figure ). Employing the standard borylative procedure, isoquinolyl borindolizine 3p was isolated as a red solid in a 68% yield. Satisfyingly, the compound was red-emissive in dichloromethane with a λmax,emof 635 nm and a broad emission between 610 and 840 nm in excellent agreement with the predicted emission value of 621 nm. Borindolizine 3p also exhibits a very large Stokes shift of 11283 cm -1 which is a dramatically higher than the typical Stokes shift observed in this series of compounds (2121 -4670 cm -1 , 3a -3o). This result strongly validates the ability of the computational model to effectively predict the absorption emission wavelengths of the borindolizine class of fluorophores, allowing for the rational design and photophysical tunability of these fluorophores.