The power conversion efficiencies of organic photovoltaics (OPVs) have grown tremendously over the last 20 years and represent a low-cost and sustainable solution for harnessing solar energy to power our residences, workplaces, and devices. Fullerene-containing OPVs are relatively expensive and have limited overlap absorbance with the solar spectrum. We used density functional theory calculation and Gaussian processes calibration to predict frontier molecular orbitals and power conversion efficiencies for over 51,000 non-fullerene acceptors with the polymeric electron-donor component, poly[N-9 0-heptadecanyl-2,7carbazole-alt-5,5-(4 0 ,7 0-di-2-thienyl-2 0 ,1 0 ,3 0-benzothiadiazole)].

The azide−dibenzocyclooctyne and transcyclooctene−tetrazine cycloadditions are both bioorthogonal and mutually orthogonal: trans-cyclooctene derivatives greatly prefer to react with tetrazines rather than azides, while dibenzocyclooctyne derivatives react with azides but not with tetrazines under physiological conditions. DFT calculations used to identify the origins of this extraordinary selectivity are reported, and design principles to guide discovery of new orthogonal cycloadditions are proposed. Two new bioorthogonal reagents, methylcyclopropene and 3,3,6,6-tetramethylthiacycloheptyne, are predicted to be mutually orthogonal in azide and tetrazine cycloadditions.A zide and tetrazine cycloadditions have become central reactions in the rapidly developing field of cellular component labeling with bioorthogonal reactions. 1−3 Bertozzi and co-workers have developed strain-promoted (3 + 2) cycloaddition reactions between azides and cyclooctynes since 2004 (Scheme 1a). 4 These reactions proceed at a rate that is sufficient for in vivo labeling without the toxic copper(I) catalysts traditionally employed in "click chemistry" involving azide cycloadditions. Several groups have developed structurally varied cyclooctyne derivatives with different chemical reactivities and physical properties. 5 Another breakthrough in this area came in 2008 with the application of inverse-electrondemand Diels−Alder reactions of 1,2,4,5-tetrazines and strained alkenes (Scheme 1b). 6 In particular, the trans-cyclooctene− tetrazine (4 + 2) cycloaddition, which has an extremely high bimolecular rate constant (k 2 = 10 2 −10 4 M −1 s −1 ), 7 is much faster than the azide−cyclooctyne (3 + 2) cycloaddition (k 2 = 10 −3 −1 M −1 s −1 ). 1c Recently, Hilderbrand and co-workers demonstrated that two bioorthogonal cycloaddition pairs are mutually orthogonal. 8 That is, as shown in Scheme 2a, transcyclooctene derivatives greatly prefer to react with tetrazines rather than azides, while dibenzocyclooctyne derivatives react with azides but not with tetrazines under physiological conditions (Scheme 2b). On the basis of this discovery, Hilderbrand and co-workers successfully realized the simultaneous labeling and imaging of two different cancer cell types in biological environments. 8 At almost the same time, Schultz, Lemke, and co-workers found that trans-cyclooctenes show extremely high selectivity toward tetrazines rather than azides in protein labeling experiments. 9 However, the cyclooctynemodified proteins couple with both tetrazine-functionalized and azide-functionalized dyes. 9 The similar reactivities of cyclooctynes with azides and tetrazines was also demonstrated in separate kinetic studies by the Bertozzi and Wang groups: tetrazines react with cyclooctynes only 1−2 orders of magnitude faster than azides do (Scheme 2c). 10 transCyclooctene, cyclooctyne, and dibenzocyclooctyne are all highly strained molecules; why do their selectivities toward azides and tetrazines under bioorthogonal cycloadditions differ

The reactivities of enamines and predistorted (strained) dipolarophiles toward perfluoroaryl azides (PFAAs) were explored experimentally and computationally. Kinetic analyses indicate that PFAAs undergo (3 + 2) cycloadditions with enamines up to 4 orders of magnitude faster than phenyl azide reacts with these dipolarophiles. DFT calculations were used to identify the origin of this rate acceleration. Orbital interactions between the cycloaddends are larger due to the relatively low-lying LUMO of PFAAs. The triazolines resulting from PFAA–enamine cycloadditions rearrange to amidines at room temperature, while (3 + 2) cycloadditions of enamines and phenyl azide yield stable, isolable triazolines. The 1,3-dipolar cycloadditions of norbornene and DIBAC also show increased reactivity toward PFAAs over phenyl azide but are slower than enamine–azide cycloadditions.

Bioorthogonal chemistries have provided tremendous insight into biomolecule structure and function. However, many popular bioorthogonal transformations are incompatible with one another, limiting their utility for studies of multiple biomolecules in tandem. We identified two reactions that can be used concurrently to tag biomolecules in complex environments: the inverse electron-demand Diels-Alder reaction of tetrazines with 1,3-disubstituted cyclopropenes, and the 1,3-dipolar cycloaddition of nitrile imines with 3,3-disubstituted cyclopropenes. Remarkably, the cyclopropenes used in these transformations differ by the placement of a single methyl group. Such orthogonally reactive scaffolds will bolster efforts to monitor multicomponent processes in cells and organisms.

The Harvard Organic Photovoltaic Dataset (HOPV15) presented in this work is a collation of experimental photovoltaic data from the literature, and corresponding quantum-chemical calculations performed over a range of conformers, each with quantum chemical results using a variety of density functionals and basis sets. It is anticipated that this dataset will be of use in both relating electronic structure calculations to experimental observations through the generation of calibration schemes, as well as for the creation of new semi-empirical methods and the benchmarking of current and future model chemistries for organic electronic applications.