Demonstration of Baird's rule complementarity in the singlet state with implications for excited-state intramolecular proton transfer

The aromatic character of an arene is proposed to switch from aromatic in the ground state (S 0) to antiaromatic in the S 1 and T 1 excited states. This behavior is known as Baird's rule and has been invoked to explain excited-state properties, primarily in the triplet state, whereas rationalization of antiaromaticity in the singlet state is less developed. This work demonstrates the first application of Baird's rule to rationalize previously unexplained experimental behavior of the singlet state process known as excited-state intramolecular proton transfer (ESIPT). Further, by analyzing the variations in isotropic magnetic shielding around the base arenes (benzene and naphthalene) of ESIPT fluorophores in the S 0 and S 1 electronic states, different shielding distributions indicate a complementarity to Baird's rule: greater aromaticity in S 0 leads to greater antiaromaticity in S 1 and vice versa. These findings have immediate application in the design of functional ESIPT fluorophores and, more generally, for photochemical reactions that are driven by the relief of antiaromaticity in the excited state. Notably, a tenet of traditional chromophore design states that expansion of conjugation generally leads to a red-shift in absorbance and emission wavelengths. The results of this study show that ESIPT fluorophores run contrary to those conventional design principles and this behavior can only be rationalized by considering Baird's rule

The Synthesis of Azaperylene-9,10-dicarboximides

The syntheses of two azaperylene 9,10-dicarboximides are presented. 1-Aza- and 1,6-diazaperylene 9,10-dicarboximides containing a 2,6-diisopropylphenyl substituent at the N-imide position were synthesized in two steps starting from naphthalene and isoquinoline derivatives

Magnetic shielding paints an accurate and easy-to-visualize portrait of aromaticity

Chemists are trained to recognize aromaticity semi-intuitively, using pictures of resonance structures and Frost-Musulin diagrams, or simple electron-counting rules such as Hückel's 4n + 2/4n rule. To quantify aromaticity one can use various aromaticity indices, each of which is a number reflecting some experimentally measured or calculated molecular property, or some feature of the molecular wavefunction, which often has no visual interpretation or may not have direct chemical relevance. We show that computed isotropic magnetic shielding isosurfaces and contour plots provide a feature-rich picture of aromaticity and chemical bonding which is both quantitative and easy-to-visualize and interpret. These isosurfaces and contour plots make good chemical sense as at atomic positions they are pinned to the nuclear shieldings which are experimentally measurable through chemical shifts. As examples we discuss the archetypal aromatic and antiaromatic molecules of benzene and square cyclobutadiene, followed by modern visual interpretations of Clar's aromatic sextet theory, the aromaticity of corannulene and heteroaromaticity.This article is published as Karadakov, Peter B., and Brett VanVeller. "Magnetic shielding paints an accurate and easy-to-visualize portrait of aromaticity." Chemical Communications 57, no. 75 (2021): 9504-9513. DOI: 10.1039/D1CC03701C. Copyright 2021 Royal Society of Chemistry. Creative Commons Attribution 3.0 Unported Licence (CC BY 3.0). Posted with permission

Highly selective staining and quantification of intracellular lipid droplets with a compact push–pull fluorophore based on benzothiadiazole

A robust lipophilic dye, based on the structures of the benzothiadiazole heterocycle, was shown to be a potent fluorescent stain for the selective imaging of lipid droplets (LDs) within both live and fixed human cells. Its small molecular framework, large Stokes shift, and vastly improved photostability over that of the current status quo, Nile Red, highlight its tremendous potential as a versatile chemical tool for facilitating LD imaging and research

Fluorescent penetration enhancers for transdermal applications

Chemical penetration enhancers are often used to enhance transdermal drug delivery. However, the fundamental mechanisms that govern the interactions between penetration enhancers and skin are not fully understood. Therefore, the goal of this work was to identify naturally fluorescent penetration enhancers (FPEs) in order to utilize well-established fluorescence techniques to directly study the behavior of FPEs within skin. In this study, 12 fluorescent molecules with amphiphilic characteristics were evaluated as skin penetration enhancers. Eight of the molecules exhibited significant activity as skin penetration enhancers, determined using skin current enhancement ratios. In addition, to illustrate the novel, direct, and non-invasive visualization of the behavior of FPEs within skin, three case studies involving the use of two-photon fluorescence microscopy (TPM) are presented, including visualizing glycerol-mitigated and ultrasound-enhanced FPE skin penetration. Previous TPM studies have indirectly visualized the effect of penetration enhancers on the skin by using a fluorescent dye to probe the transdermal pathways of the enhancer. These effects can now be directly visualized and investigated using FPEs. Finally, future studies are proposed for generating FPE design principles. The combination of FPEs with fluorescence techniques represents a useful novel approach for obtaining physical insights on the behavior of penetration enhancers within the skin.National Institutes of Health (U.S.) (Grant EB-00351)Massachusetts Institute of Technology. Institute for Soldier Nanotechnologies (Grant DAAD-19-02-D-002)National Science Foundation (U.S.). Graduate Research FellowshipConselho Nacional de Pesquisas (Brazil)Fundacao de Amparo a Pesquisa do Estado de Sao Paul

Biocompatible post-polymerization functionalization of a water soluble poly(p-phenylene ethynylene)

A biocompatible post-polymerization functionalization reaction takes advantage of a polymer's structural motif for the controllable attachment of biotin as a model biosensor that responds to streptavidin.Natural Sciences and Engineering Research Council of Canada (NSERC)Massachusetts Institute of Technology. Institute for Soldier NanotechnologiesUnited States. Army Research Office (Contract W911NF-07-D-004

Probing O-H Bonding Through Proton Detected 1H-17O Double Resonance Solid-State NMR Spectroscopy

The ubiquity of oxygen in organic, inorganic, and biological systems has stimulated the application and development of 17O solid-state NMR spectroscopy as a probe of molecular structure and dynamics. Unfortunately, 17O solid-state NMR experiments are often hindered by the combination of broad NMR signals and low sensitivity. Here, it is demonstrated that fast MAS and proton detection with the D-RINEPT pulse sequence can be generally applied to enhance the sensitivity and resolution of 17O solid-state NMR experiments. Complete 2D 17O→1H D-RINEPT correlation NMR spectra were typically obtained in fewer than 10 hours from less than 10 milligrams of material, with low to moderate 17O enrichment (less than 20%). 2D 1H-17O correlation solid-state NMR spectra allow overlapping oxygen sites to be resolved on the basis of proton chemical shifts or by varying the mixing time used for 1H-17O magnetization transfer. In addition, J-resolved or separated local field (SLF) blocks can be incorporated into the D-RINEPT pulse sequence to allow direct measurement of one-bond 1H-17O scalar coupling constants (1JOH) or 1H-17O dipolar couplings (DOH), respectively; the latter of which can be used to infer 1H-17O bond lengths. 1JOH and DOH calculated from planewave density functional theory (DFT) show very good agreement with experimental values. Therefore, the 2D 1H-17O correlation experiments, 1H-17O scalar and dipolar couplings, and planewave DFT calculations provide a method to precisely determine proton positions relative to oxygen atoms. This capability opens new opportunities to probe interactions between oxygen and hydrogen in a variety of chemical systems