Application of Inverse Design Approaches to the Discovery of Nonlinear Optical Switches.

Molecular switches, in which a stimulus induces a large and reversible change in molecular properties, are of significant interest in the domain of photonics. Due to their commutable redox states with distinct nonlinear optical (NLO) properties, hexaphyrins have emerged as a novel platform for multistate switches in nanoelectronics. In this study, we employ an inverse design algorithm to find functionalized 26R→28R redox switches with maximal ßHRS contrast. We focus on the role of core modifications, since a synergistic effect with meso-substitutions was recently found for the 30R-based switch. In contrast to these findings, the inverse design optima and subsequent database analysis of 26R-based switches confirm that core modifications are generally not favored when high NLO contrasts are targeted. Moreover, while push-pull combinations enhance the NLO contrast for both redox switches, they prefer a different arrangement in terms of electron-donating and electron-withdrawing functional groups. Finally, we aim at designing a three-state 26R→28R→ 30R switch with a similar NLO response for both ON states. Even though our best-performing three-state switch follows the design rules of the 30R-based component, our chemical compound space plots show that well-performing three-state switches can be found in regions shared by high-responsive 26R and 30R structures.

The electrophilic aromatic bromination of benzenes: mechanistic and regioselective insights from density functional theory.

The HBr-assisted electrophilic aromatic bromination of benzene, anisole and nitrobenzene was investigated using static DFT calculations in gas phase and implicit apolar (CCl4) and polar (acetonitrile) solvent models at the ωB97X-D/cc-pVTZ level of theory. The reaction profiles corresponding to either a direct substitution reaction or an addition-elimination process were constructed and insight into the preferred regioselectivity was provided using a combination of conceptual DFT reactivity indices, aromaticity indices, Wiberg bond indices and the non-covalent interaction index. Our results show that under the considered reaction conditions the bromination reaction preferentially occurs through an addition-elimination mechanism and without formation of a stable charged Wheland intermediate. The ortho/para directing effect of the electron-donating methoxy-group in anisole was ascribed to a synergy between strong electron delocalisation and attractive interactions. In contrast, the preferred meta-addition on nitrobenzene could not be traced back to any of these effects, nor to the intrinsic reactivity property of the reactant. In this case, an electrostatic clash between the ipso-carbon of the ring and the nitrogen atom resulting from the later nature of the rate-determining step, with respect to anisole, appeared to play a crucial role.

Designing hexaphyrins for high-potential NLO switches: the synergy of core-modifications and meso-substitutions.

Due to the enormous size of the chemical compound space, usually only small regions are traversed with traditional direct molecular design approaches making the discovery for novel functionalized molecules for nonlinear optical applications challenging. By applying inverse molecular design algorithms, we aim to efficiently explore larger regions of the compound space in search of promising hexaphyrin-based molecular switches as measured by their first-hyperpolarizability (ßHRS) contrast. We focus on the 28R → 30R switch with a functionalization pattern allowing for centrosymmetric OFF states yielding zero ßHRS response. This switch is particularly challenging as full meso-substitution with a single type of functional group or core-modifications result in almost no contrast enhancement. We carried out four inverse design procedures during which two sets of core-modifications and three sets of meso-substitutions sites were systematically optimized. All 4 optimal switches are characterized by a mix of meso-substitutions and core-modifications, of which the best performing switch yields a 10-fold improvement over the parent macrocycle. Throughout the inverse design procedures, we collected and analyzed a database biased towards high NLO contrasts that contains 277 different patterns for hexaphyrin-based switches. We derived three design rules to obtain highly functional 28R → 30R NLO switches: (I) a combination of 2 strong EWG and 1 EDG group is the ideal recipe for increasing the NLO contrast, though their position also plays an important role. (II) The type of core-modification is less important when only the diagonal positions are core-modified. Switches with 4 core-modifications show a clear preference for oxygen. (III) Keeping centrosymmetry in the OFF state remains highly beneficial given the investigated functionalization pattern. Finally, we have demonstrated that combining meso-substitutions with core-modifications can synergistically improve the NLO contrast.

Heteroaryl sulfonamide synthesis: scope and limitations.

Heteroaryl sulfonamides are important structural motifs in the medicinal and agrochemical industries. However, their synthesis often relies on the use of heteroaryl sulfonyl chlorides, which are unstable and toxic reagents. Herein, we report a protocol that allows direct oxidative coupling of heteroaryl thiols and primary amines, readily available and inexpensive commodity chemicals. The transformation proceeds under mild reaction conditions and yields the desired N-alkylated sulfonamides in good yields. N-alkyl heteroaryl sulfonamides can be further transformed using a microwave-promoted Fukuyama-Mitsunobu reaction to N,N-dialkyl heteroaryl sulfonamides. The developed protocols thus enable the preparation of previously difficult to prepare sulfonamides (toxic reagents, harsh conditions, and low yields) under mild conditions.

Fine-Tuning of Nonlinear Optical Contrasts of Hexaphyrin-Based Molecular Switches Using Inverse Design.

In the search for new nonlinear optical (NLO) switching devices, expanded porphyrins have emerged as ideal candidates thanks to their tunable chemical and photophysical properties. Introducing meso-substituents to these macrocycles is a successful strategy to enhance the NLO contrasts. Despite its potential, the influence of meso-substitution on their structural and geometrical properties has been scarcely investigated. In this work, we pursue to grasp the underlying pivotal concepts for the fine-tuning of the NLO contrasts of hexaphyrin-based molecular switches, with a particular focus on the first hyperpolarizability related to the hyper-Rayleigh scattering (ß HRS ). Building further on these concepts, we also aim to develop a rational design protocol. Starting from the (un)substituted hexaphyrins with various π-conjugation topologies and redox states, structure-property relationships are established linking aromaticity, photophysical properties and ß HRS responses. Ultimately, inverse molecular design using the best-first search algorithm is applied on the most favorable switches with the aim to further explore the combinatorial chemical compound space of meso-substituted hexaphyrins in search of high-contrast NLO switches. Two definitions of the figure-of-merit of the switch performance were used as target objectives in the optimization problem. Several meso-substitution patterns and their underlying characteristics are identified, uncovering molecular symmetry and the electronic nature of the substituents as the key players for fine-tuning the ß HRS values and NLO contrasts of hexaphyrin-based switches.