22959-81-5Relevant academic research and scientific papers
Lewis or Br?nsted? A Rectification of the Acidic and Aromatic Nature of Boranol-Containing Naphthoid Heterocycles
Ang, Hwee Ting,Ferguson, Michael J.,Hall, Dennis G.,Johnson, Matthew A.,Kazmi, M. Zain H.,Paladino, Marco,Rygus, Jason P. G.
, p. 10143 - 10156 (2021/07/21)
Boron-containing heterocycles are important in a variety of applications from drug discovery to materials science; therefore a clear understanding of their structure and reactivity is desirable to optimize these functions. Although the boranol (B-OH) unit of boronic acids behaves as a Lewis acid to form a tetravalent trihydroxyborate conjugate base, it has been proposed that pseudoaromatic hemiboronic acids may possess sufficient aromatic character to act as Br?nsted acids and form a boron oxy conjugate base, thereby avoiding the disruption of ring aromaticity that would occur with a tetravalent boronate anion. Until now no firm evidence existed to ascertain the structure of the conjugate base and the aromatic character of the boron-containing ring of hemiboronic "naphthoid"isosteres. Here, these questions are addressed with a combination of experimental, spectroscopic, X-ray crystallographic, and computational studies of a series of model benzoxazaborine and benzodiazaborine naphthoids. Although these hemiboronic heterocycles are unambiguously shown to behave as Lewis acids in aqueous solutions, boraza derivatives possess partial aromaticity provided their nitrogen lone electron pair is sufficiently available to participate in extended delocalization. As demonstrated by dynamic exchange and crossover experiments, these heterocycles are stable in neutral aqueous medium, and their measured pKa values are consistent with the ability of the endocyclic heteroatom substituent to stabilize a partial negative charge in the conjugate base. Altogether, this study corrects previous inaccuracies and provides conclusions regarding the properties of these compounds that are important toward the methodical application of hemiboronic and other boron heterocycles in catalysis, bioconjugation, and medicinal chemistry.
Diazaborines Are a Versatile Platform to Develop ROS-Responsive Antibody Drug Conjugates**
Aguiar, Sandra I.,André, Ana S.,António, Jo?o P. M.,Bernardes, Gon?alo J. L.,Carvalho, Joana Inês,Dias, Joana N. R.,Faustino, Hélio,Gois, Pedro M. P.,Lopes, Ricardo M. R. M.,Veiros, Luis F.,da Silva, Frederico A.
supporting information, p. 25914 - 25921 (2021/11/09)
Antibody–drug conjugates (ADCs) are a new class of therapeutics that combine the lethality of potent cytotoxic drugs with the targeting ability of antibodies to selectively deliver drugs to cancer cells. In this study we show for the first time the synthesis of a reactive-oxygen-species (ROS)-responsive ADC (VL-DAB31-SN-38) that is highly selective and cytotoxic to B-cell lymphoma (CLBL-1 cell line, IC50 value of 54.1 nM). The synthesis of this ADC was possible due to the discovery that diazaborines (DABs) are a very effective ROS-responsive unit that are also very stable in buffer and in plasma. DFT calculations performed on this system revealed a favorable energetic profile (ΔGR=?74.3 kcal mol?1) similar to the oxidation mechanism of aromatic boronic acids. DABs’ very fast formation rate and modularity enabled the construction of different ROS-responsive linkers featuring self-immolative modules, bioorthogonal functions, and bioconjugation handles. These structures were used in the site-selective functionalization of a VL antibody domain and in the construction of the homogeneous ADC.
Synthesis, characterization, and antibacterial activity of structurally complex 2-acylated 2,3,1-benzodiazaborines and related compounds
Kanichar, Divya,Roppiyakuda, Lance,Kosmowska, Ewa,Faust, Michelle A.,Tran, Kim P.,Chow, Felicia,Buglo, Elena,Groziak, Michael P.,Sarina, Evan A.,Olmstead, Marilyn M.,Silva, Isba,Xu, H. Howard
, p. 1381 - 1397 (2015/04/14)
A set of 2-acylated 2,3,1-benzodiazaborines and some related boron heterocycles were synthesized, characterized, and tested for antibacterial activity against Escherichia coli and Mycobacterium smegmatis. By high-field solution NMR, the heretofore unknown
Synthesis, characterization, and antibacterial activity of structurally complex 2-Acylated 2,3,1-benzodiazaborines and related compounds
Kanichar, Divya,Roppiyakuda, Lance,Kosmowska, Ewa,Faust, Michelle A.,Tran, Kim P.,Chow, Felicia,Buglo, Elena,Groziak, Michael P.,Sarina, Evan A.,Olmstead, Marilyn M.,Silva, Isba,Xu, H. Howard
, p. 1381 - 1397 (2015/04/14)
A set of 2-acylated 2,3,1-benzodiazaborines and some related boron heterocycles were synthesized, characterized, and tested for antibacterial activity against Escherichia coli and Mycobacterium smegmatis. By high-field solution NMR, the heretofore unknown class of 2-acyl-1-hydroxy-2,3,1-diazaborines has been found to be able to exist in several interconvertable structural forms along a continuum comprised of an open hydrazone a, a monomeric B-hydroxy diazaborine b, and an anhydro dimer c. X-Ray crystallography of one of the anhydro dimers, 17c, revealed it to have an unprecedented structure featuring a double intramolecular O→B chelation. The crystal structure of another compound, 37, showed it to be based on a new pentacyclic B heterocycle framework. Nine compounds were found to possess activities against E. coli, and two others were active against M. smegmatis. The finding that these two contain isoniazid covalently embedded in their structures suggests that they might possibly be acting as prodrugs of this well-known antituberculosis agent in vivo.
Planar boron heterocycles with nucleic acid-like hydrogen-bonding motifs
Groziak, Michael P.,Chen, Liya,Yi, Lin,Robinson, Paul D.
, p. 7817 - 7826 (2007/10/03)
To promote the development of boron-containing purine analogues that exist in planar, non-zwitterionic dominant structural form. in aqueous solution, rigorous solution and solid state structural analyses of 1-hydroxy-1H-2,3,1-benzoxazaborine (1), 1,2-dihydro-1-hydroxy-2,3,1-benzodiazabo (2), and related 2,3,1-benzodiheteraborines were undertaken. With the aid of isotope-enriched compounds, a multisolvent 1H, 13C, 11B, and 15N NMR spectroscopic analysis of 1 and 2 was conducted, providing structurally-diagnostic chemical shift data for all non-oxygen atoms that constitute their heterocyclic peripheries. In addition, single-crystal X-ray diffraction analyses of 1 and 2 were performed. In stark contrast to their 2,4,1 isomeric counterparts, the 2,3,1-benzoxaza- and benzodiazaborines exist in planar structural form in protic solution and in the solid state and display proton dissociative and associative tendencies reflective of the predominant Bronsted, yet still Lewis acidic-capable character of the B-OH group together with the basic one at the C4-N3 imine group. In the solid state, 1 and 2 display intermolecular hydrogen-bonding patterns not too dissimilar from the motifs of certain natural nucleic acid bases. Diazaborine 2 was shown by VT-NMR to undergo a triple hydrogen-bonding solution association with a 2',3',5'-tri-O-protected cytidine in a demonstration of one biomimetic potential held by a 1-hydroxy-2,3,1-diheteraborine periphery. In general, 1, 2, and related 1-hydroxy-2,3,1-benzodiheteraborine heterocycles were found to be characterized by an environment-dependent O1 → N3 Bronsted prototropy and B-OH group Bronsted/Lewis acid ambidency so sensitive and subtle that certain past difficulties encountered in attempts to delineate their physicochemical properties now become readily appreciated.
