Substituent Effects on the Solubility and Electronic Properties of the Cyanine Dye Cy5: Density Functional and Time-Dependent Density Functional Theory Calculations

Abstract

The aggregation ability and exciton dynamics of dyes are largely affected by properties of the dye monomers. To facilitate aggregation and improve excitonic function, dyes can be engineered with substituents to exhibit optimal key properties, such as hydrophobicity, static dipole moment differences, and transition dipole moments. To determine how electron donating (D) and electron withdrawing (W) substituents impact the solvation, static dipole moments, and transition dipole moments of the pentamethine indocyanine dye Cy5, density functional theory (DFT) and time-dependent (TD-) DFT calculations were performed. The inclusion of substituents had large effects on the solvation energy of Cy5, with pairs of withdrawing substituents (W-W pairs) exhibiting the most negative solvation energies, suggesting dyes with W-W pairs are more soluble than others. With respect to pristine Cy5, the transition dipole moment was relatively unaffected upon substitution while numerous W-W pairs and pairs of donating and withdrawing substituents (D-W pairs) enhanced the static dipole difference. The increase in static dipole difference was correlated with an increase in the magnitude of the sum of the Hammett constants of the substituents on the dye. The results of this study provide insight into how specific substituents affect Cy5 monomers and which pairs can be used to engineer dyes with desired properties.

Synthesis of Substituted Cy5 Phosphoramidite Derivatives and Their Incorporation into Oligonucleotides Using Automated DNA Synthesis

“… 27 Additionally, the electron-donating or electron-withdrawing character of substituents placed at the 5,5′-positions enables the tuning of photophysical properties, such as absorption and emission maxima. 24 Thus, we designed and synthesized a series of Cy5 derivatives ready for phosphoramidite conversion with different peripheral substituents including n -hexyloxy (Cy5-hex), 2-[2-(2-methoxyethoxy)ethoxy]ethoxy (Cy5-Peg), tert -butyl (Cy5- t Bu), and chloro (Cy5-Cl) groups, see Figure 1 . Hexyloxy and Peg substituents possess similar electron-donating capacities but are hydrophobic and hydrophilic, respectively.…”

First-principles studies of substituent effects on squaraine dyes

“…The Gaussian 16 soware package 69 was used to perform density functional theory (DFT) and time-dependent density functional theory (TD-DFT) calculations. DFT has proven to provide insight in the investigation of dye properties, [65][66][67]70 and there has been extensive work addressing best practices in employing this method, such as appropriate exchangecorrelation functionals to represent electron-electron interactions in the uorescing dyes similar to squaraine dyes. [71][72][73][74] The dyes were built and initially relaxed with the molecular editing soware Avogadro 75 using the UFF 76 method.…”

Counterion Pairing Effects on a Flavylium Heptamethine Dye†

“…Solvent was removed under reduced pressure with a Büchi Rotovapor with a Welch self-cleaning dry vacuum pump and further dried with a Welch DuoSeal pump. Nuclear magnetic resonance ( 1 H-NMR, 13 C-NMR, 11 B-NMR, 19 F-NMR) spectra were taken on Bruker Advance AV-400 or AV-500 and processed with MestReNova or TopSpin software. All 1 H-NMR and 13 C-NMR peaks are reported in ppm in reference to residual solvent signals.…”

“…More detailed procedures and characterization can be found within the supporting information. Due to having the same core structure, there is little change in 1 H NMR and 13 C NMR (Figure S1) between counterion derivatives for the flavylium heptamethine, and consequently 11 B NMR and 19 F NMR were utilized to help distinguish between fluorophores with different counterions.…”

“…Minimizing aggregate states can be achieved through increasing solubility or shielding the charged fluorophore so it can no longer stack upon itself. For example, attaching solubilizing groups such as sulfonates can increase water solubility for biological applications (10)(11)(12)(13)(14). The attachment of sterically bulky moieties can enable solubility in more nonpolar solvents, allowing processing of dyes for the development of solar cells and all optical signal processing devices (15,16).…”