Evaluating and clustering retrosynthesis pathways with learned strategy

With recent advances in the computer-aided synthesis planning (CASP) powered by data science and machine learning, modern CASP programs can rapidly identify thousands of potential pathways for a given target molecule. However, the lack of a holistic pathway evaluation mechanism makes it challenging to systematically prioritize strategic pathways except for using some simple heuristics. Herein, we introduce a data-driven approach to evaluate the relative strategic levels of retrosynthesis pathways using a dynamic tree-structured long short-term memory (tree-LSTM) model. We first curated a retrosynthesis pathway database, containing 238k patent-extracted pathways along with ∼55 M artificial pathways generated from an open-source CASP program, ASKCOS. The tree-LSTM model was trained to differentiate patent-extracted and artificial pathways with the same target molecule in order to learn the strategic relationship among single-step reactions within the patent-extracted pathways. The model achieved a top-1 ranking accuracy of 79.1% to recognize patent-extracted pathways. In addition, the trained tree-LSTM model learned to encode pathway-level information into a representative latent vector, which can facilitate clustering similar pathways to help illustrate strategically diverse pathways generated from CASP programs.

Tree-structured long short-term memory neural model learns to understand the retrosynthesis design strategies from patent-extracted retrosynthetic pathway data.     

Universal quenching of common fluorescent probes by water and alcohols

Although biological imaging is mostly performed in aqueous media, it is hardly ever considered that water acts as a classic fluorescence quencher for organic fluorophores. By investigating the fluorescence properties of 42 common organic fluorophores recommended for biological labelling, we demonstrate that H₂O reduces their fluorescence quantum yield and lifetime by up to threefold and uncover the underlying fluorescence quenching mechanism. We show that the quenching efficiency is significantly larger for red-emitting probes and follows an energy gap law. The fluorescence quenching finds its origin in high-energy vibrations of the solvent (OH groups), as methanol and other linear alcohols are also found to quench the emission, whereas it is restored in deuterated solvents. Our observations are consistent with a mechanism by which the electronic excitation of the fluorophore is resonantly transferred to overtones and combination transitions of high-frequency vibrational stretching modes of the solvent through space and not through hydrogen bonds. Insight into this solvent-assisted quenching mechanism opens the door to the rational design of brighter fluorescent probes by offering a justification for protecting organic fluorophores from the solvent via encapsulation.

Overtones and combinations of O–H vibrations in the solvent efficiently quench red-emitting fluorophores by resonant energy transfer.     

Platinum Indolylphosphine Fluorido and Polyfluorido Complexes: An Interplay between Cyclometallation,Fluoride Migration,and Hydrogen Bonding

The reaction of [PtCl₂(COD)] (COD=1,5-cyclooctadiene) with diisopropyl-2-(3-methyl)indolylphosphine (iPr₂P(C₉H₈N)) led to the formation of the platinum(ii ) chlorido complexes, cis-[PtCl₂{iPr₂P(C₉H₈N)}₂] ( 1 ) and trans-[PtCl₂{iPr₂P(C₉H₈N)}₂] ( 2 ). The cis-complex 1 reacted with NEt₃ yielding the complex cis-[PtCl{κ²-(P,N)-iPr₂P(C₉H₇N)}{iPr₂P(C₉H₈N)}] ( 3 ) bearing a cyclometalated κ²-(P,N)-phosphine ligand, while the isomer 2 with a trans-configuration did not show any reactivity towards NEt₃. Treatment of 1 or 3 with (CH₃)₄NF (TMAF) resulted in the formation of the twofold cyclometalated complex cis-[Pt{κ²-(P,N)-iPr₂P(C₉H₇N)}₂] ( 4 ). The molecular structures of the complexes 1–4 were determined by single-crystal X-ray diffraction. The fluorido complex cis-[PtF{κ²-(P,N)-iPr₂P(C₉H₇N)}{iPr₂P(C₉H₈N)}] ⋅ (HF)₄ ( 5 ⋅ (HF)₄) was formed when complex 4 was treated with different hydrogen fluoride sources. The Pt(ii ) fluorido complex 5 ⋅ (HF)₄ exhibits intramolecular hydrogen bonding in its outer coordination sphere between the fluorido ligand and the NH group of the 3-methylindolyl moiety. In contrast to its chlorido analogue 3 , complex 5 ⋅ (HF)₄ reacted with CO or the ynamide 1-(2-phenylethynyl)-2-pyrrolidinone to yield the complexes trans-[Pt(CO){κ²-(P,C)-iPr₂P(C₉H₇NCO)}{iPr₂P(C₉H₈N)}][F(HF)₄] ( 7 ) and a complex, which we suggest to be cis-[Pt{C=C(Ph)OCN(C₃H₆)}{κ²-(P,N)-iPr₂P(C₉H₇N)}{iPr₂P(C₉H₈N)}][F(HF)₄] ( 9 ), respectively. The structure of 9 was assigned on the basis of DFT calculations as well as NMR and IR data. Hydrogen bonding of HF and NH to fluoride was proven to be crucial for the existence of 7 and 9 .     

Reductive Cross-Coupling of a Vinyl Thianthrenium Salt and Secondary Alkyl Iodides

We report the first reductive vinylation of alkyl iodides. The reaction uses a vinyl thianthrenium salt, a palladium catalyst, and an alkyl zinc intermediate formed in situ to trap the L_nPd^II(vinyl) complex formed after oxidative addition before it undergoes undesired homocoupling to form butadiene.     

THE IMPACT OF THE NATIONAL NUMERACY STRATEGY IN YEAR 4 (II): TEACHING

The Nuffield Year 4 project set out to examine selected aspects of the impact of the National Numeracy Strategy (NNS) in primary schools by using comparable data on Year 4 pupil attainment and teaching collected in 1997/98 and 2001/02, two years before and two years after the introduction of the Numeracy Strategy. In this second paper we address the following questions:

• How and to what extent has numeracy teaching in Year 4 changed?

• Why have these changes occurred?

• How can we improve future implementation of reforms?

• How can we inform continuing professional development?

     

Irregularity strength of digraphs

It is an elementary exercise to show that any non-trivial simple graph has two vertices with the same degree. This is not the case for digraphs and multigraphs. We consider generating irregular digraphs from arbitrary digraphs by adding multiple arcs. To this end, we define an irregular labeling of a digraph D to be an arc-labeling of the digraph such that the ordered pairs of the sums of the in-labels and out-labels at each vertex are all distinct. We define the strength of D to be the smallest of the maximum labels used across all irregular labelings. Similar definitions for graphs have been studied extensively and a different formulation of digraph irregularity was given in [H. Hackett, Irregularity strength of graphs and digraphs, Masters Thesis, University of Louisville, 1995]. Here we continue the study of irregular labelings of digraphs. We give a general lower bound on and determine exactly for tournaments, directed paths and cycles and the orientation of the path where all vertices have either in-degree 0 or out-degree 0. We also determine the irregularity strength of a union of directed cycles and a union of directed paths, the latter which requires a new result pertaining to finding circuits of given lengths containing prescribed vertices in the complete symmetric digraph with loops.     

Rook Poset Equivalence of Ferrers Boards

A natural construction due to K. Ding yields Schubert varieties from Ferrers boards. The poset structure of the Schubert cells in these varieties is equal to the poset of maximal rook placements on the Ferrers board under the Bruhat order. We determine when two Ferrers boards have isomorphic rook posets. Equivalently, we give an exact categorization of when two Ding Schubert varieties have identical Schubert cell structures. This also produces a complete classification of isomorphism types of lower intervals of 312-avoiding permutations in the Bruhat order.     

A Flaw in the Use of Minimal Defining Sets for Secret Sharing Schemes

It is shown that in some cases it is possible to reconstruct a block design uniquely from incomplete knowledge of a minimal defining set for . This surprising result has implications for the use of minimal defining sets in secret sharing schemes.