Internally versus Externally Solvated Derivatives of Doubly Bridged 1,4-Dilithio-2-butene: Structures and Dynamic Behavior. A “T” Shaped Dimeric Cluster in the Solid State

X-ray crystallographic NMR and calculational modeling studies using B3LYP/6-311G* of selected dilithium derivatives of the 1,3-butadiene dianion including <i>cis</i>-dilithio-1,4-bis­(TMS)-2-butene·(TMEDA)₂ <b>2</b>, internally solvated <i>cis</i>-dilithio-1,4-bis­[bis­(2-methoxyethyl)­aminomethyldimethylsilyl]-2-butene <b>5</b>, and using only modeling, 1,4-dilithio-2-butene·(TMEDA)₂ <b>9</b> reveal remarkably similar structural and NMR parameters. In the solid, <b>5</b> consists of unusual “T” shaped dynamic clusters. In all three bridging lithiums are sited between 1.8 and 1.9 Å normal to the centroids of opposite faces of the near coplanar of the 2-butene component. Typical bond lengths of the latter are 1.458 ± 0.004, 1.385 ± 0.006, and 1.459 ± 0.003 Å, for C1–C2, C2–C3, and C3–C4, respectively. The ¹³C chemical shifts lie within the ranges δ 21 ± 0.5, 99 ± 0.7, 99 ± 0.7 and 21 ± 0.5 for C1, C2 and C3 together, and C4, respectively. Dynamic ¹³C NMR provides activation parameters for nitrogen inversion in <b>2</b> and <b>5</b>, overall molecular inversion of <b>5</b>, and conformational interconversion of <b>2</b>

Internally versus Externally Solvated Derivatives of Doubly Bridged 1,4-Dilithio-2-butene: Structures and Dynamic Behavior. A “T” Shaped Dimeric Cluster in the Solid State

X-ray crystallographic NMR and calculational modeling studies using B3LYP/6-311G* of selected dilithium derivatives of the 1,3-butadiene dianion including <i>cis</i>-dilithio-1,4-bis­(TMS)-2-butene·(TMEDA)₂ <b>2</b>, internally solvated <i>cis</i>-dilithio-1,4-bis­[bis­(2-methoxyethyl)­aminomethyldimethylsilyl]-2-butene <b>5</b>, and using only modeling, 1,4-dilithio-2-butene·(TMEDA)₂ <b>9</b> reveal remarkably similar structural and NMR parameters. In the solid, <b>5</b> consists of unusual “T” shaped dynamic clusters. In all three bridging lithiums are sited between 1.8 and 1.9 Å normal to the centroids of opposite faces of the near coplanar of the 2-butene component. Typical bond lengths of the latter are 1.458 ± 0.004, 1.385 ± 0.006, and 1.459 ± 0.003 Å, for C1–C2, C2–C3, and C3–C4, respectively. The ¹³C chemical shifts lie within the ranges δ 21 ± 0.5, 99 ± 0.7, 99 ± 0.7 and 21 ± 0.5 for C1, C2 and C3 together, and C4, respectively. Dynamic ¹³C NMR provides activation parameters for nitrogen inversion in <b>2</b> and <b>5</b>, overall molecular inversion of <b>5</b>, and conformational interconversion of <b>2</b>

Internally versus Externally Solvated Derivatives of Doubly Bridged 1,4-Dilithio-2-butene: Structures and Dynamic Behavior. A “T” Shaped Dimeric Cluster in the Solid State

X-ray crystallographic NMR and calculational modeling studies using B3LYP/6-311G* of selected dilithium derivatives of the 1,3-butadiene dianion including <i>cis</i>-dilithio-1,4-bis­(TMS)-2-butene·(TMEDA)₂ <b>2</b>, internally solvated <i>cis</i>-dilithio-1,4-bis­[bis­(2-methoxyethyl)­aminomethyldimethylsilyl]-2-butene <b>5</b>, and using only modeling, 1,4-dilithio-2-butene·(TMEDA)₂ <b>9</b> reveal remarkably similar structural and NMR parameters. In the solid, <b>5</b> consists of unusual “T” shaped dynamic clusters. In all three bridging lithiums are sited between 1.8 and 1.9 Å normal to the centroids of opposite faces of the near coplanar of the 2-butene component. Typical bond lengths of the latter are 1.458 ± 0.004, 1.385 ± 0.006, and 1.459 ± 0.003 Å, for C1–C2, C2–C3, and C3–C4, respectively. The ¹³C chemical shifts lie within the ranges δ 21 ± 0.5, 99 ± 0.7, 99 ± 0.7 and 21 ± 0.5 for C1, C2 and C3 together, and C4, respectively. Dynamic ¹³C NMR provides activation parameters for nitrogen inversion in <b>2</b> and <b>5</b>, overall molecular inversion of <b>5</b>, and conformational interconversion of <b>2</b>

Dual-Cavity Basket Promotes Encapsulation in Water in an Allosteric Fashion

We prepared dual-cavity basket <b>1</b> to carry six (<i>S</i>)-alanine residues at the entrance of its two juxtaposed cavities (289 ų). With the assistance of ¹H NMR spectroscopy and calorimetry, we found that <b>1</b> could trap a single molecule of <b>4</b> (<i>K</i>₁ = 1.45 ± 0.40 × 10⁴ M^–1, ITC), akin in size (241 ų) and polar characteristics to nerve agent VX (289 ų). The results of density functional theory calculations (DFT, M06-2X/6-31G*) and experiments (¹H NMR spectroscopy) suggest that the negative homotropic allosterism arises from the guest forming C–H···π contacts with all three of the aromatic walls of the occupied basket’s cavity. In response, the other cavity increases its size and turns rigid to prevent the formation of the ternary complex. A smaller guest <b>6</b> (180 ų), akin in size and polar characteristics to soman (186 ų), was also found to bind to dual-cavity <b>1</b>, although giving both binary [<b>1</b>⊂<b>6</b>] and ternary [<b>1</b>⊂<b>6</b>₂] complexes (<i>K</i>₁ = 7910 M^–1 and <i>K</i>₂ = 2374 M^–1, ¹H NMR spectroscopy). In this case, the computational and experimental (¹H NMR spectroscopy) results suggest that only two aromatic walls of the occupied basket’s cavity form C–H···π contacts with the guest to render the singly occupied host flexible enough to undergo additional structural changes necessary for receiving another guest molecule. The structural adaptivity of dual-cavity baskets of type <b>1</b> is unique and important for designing multivalent hosts capable of effectively sequestering targeted guests in an allosteric manner to give stable supramolecular polymers

Assembly of Amphiphilic Baskets into Stimuli-Responsive Vesicles. Developing a Strategy for the Detection of Organophosphorus Chemical Nerve Agents

We designed basket <b>1</b> to comprise a <i>C</i>₃-symmetric hydrophobic cage (477 ų) at its southern edge and three polar ammonium caps at the northern edge. This amphiphilic molecule was observed to assemble into large unilamellar vesicles (350 nm, TEM) in water and thereby entrap dimethyl phenylphosphonate (184 ų) in its cavity (<i>K</i>_app = (1.97 ± 0.02) × 10³ M^–1). The entrapment of the organophosphonate, akin to soman in size (186 ų), triggers the transformation of the vesicular material into nanoparticles (100 nm, TEM). Stimuli-responsive vesicles, containing baskets of type <b>1</b> in their bilayer membrane, are unique assemblies and important for obtaining novel sensing devices

Assembly of Amphiphilic Baskets into Stimuli-Responsive Vesicles. Developing a Strategy for the Detection of Organophosphorus Chemical Nerve Agents

We designed basket <b>1</b> to comprise a <i>C</i>₃-symmetric hydrophobic cage (477 ų) at its southern edge and three polar ammonium caps at the northern edge. This amphiphilic molecule was observed to assemble into large unilamellar vesicles (350 nm, TEM) in water and thereby entrap dimethyl phenylphosphonate (184 ų) in its cavity (<i>K</i>_app = (1.97 ± 0.02) × 10³ M^–1). The entrapment of the organophosphonate, akin to soman in size (186 ų), triggers the transformation of the vesicular material into nanoparticles (100 nm, TEM). Stimuli-responsive vesicles, containing baskets of type <b>1</b> in their bilayer membrane, are unique assemblies and important for obtaining novel sensing devices

Formation Mechanisms, Structure, Solution Behavior, and Reactivity of Aminodiborane

A facile synthesis of cyclic aminodiborane (NH₂B₂H₅, ADB) from ammonia borane (NH₃·BH₃, AB) and THF·BH₃ has made it possible to determine its important characteristics. Ammonia diborane (NH₃BH₂(μ-H)­BH₃, AaDB) and aminoborane (NH₂BH₂, AoB) were identified as key intermediates in the formation of ADB. Elimination of molecular hydrogen occurred from an ion pair, [H₂B­(NH₃) (THF)]⁺[BH₄]⁻. Protic-hydridic hydrogen scrambling was proved on the basis of analysis of the molecular hydrogen products, ADB and other reagents through ²H NMR and MS, and it was proposed that the scrambling occurred as the ion pair reversibly formed a BH₅-like intermediate, [(THF)­BH₂NH₂]­(η²-H₂)­BH₃. Loss of molecular hydrogen from the ion pair led to the formation of AoB, most of which was trapped by BH₃ to form ADB with a small amount oligomerizing to (NH₂BH₂)_<i>n</i>. Theoretical calculations showed the thermodynamic feasibility of the proposed intermediates and the activation processes. The structure of the ADB·THF complex was found from X-ray single crystal analysis to be a three-dimensional array of zigzag chains of ADB and THF, maintained by hydrogen and dihydrogen bonding. Room temperature exchange of terminal and bridge hydrogens in ADB was observed in THF solution, while such exchange was not observed in diethyl ether or toluene. Both experimental and theoretical results confirm that the B–H–B bridge in ADB is stronger than that in diborane (B₂H₆, DB). The B–H–B bridge is opened when ADB and NaH react to form sodium aminodiboronate, Na­[NH₂(BH₃)₂]. The structure of the sodium salt as its 18-crown-6 ether adduct was determined by X-ray single crystal analysis

Highly Efficient Regioselective Synthesis of 2‑Imino-4-oxothiazolidin-5-ylidene Acetates via a Substitution-Dependent Cyclization Sequence under Catalyst-Free Conditions at Ambient Temperature

A green and efficient method for the synthesis of newer 2-imino-4-oxothiazolidin-5-ylidene acetate derivatives under catalyst-free conditions by simply stirring symmetrical and unsymmetrical 1,3-diarylthioureas with dialkyl acetylenedicarboxylates in ethanol at room temperature has been developed. Interestingly, the regioselective synthesis affords the 2-imino-4-oxothiazolidin-5-ylidene acetate derivatives: the amine nitrogen bonded to an electron-withdrawing substituent becomes part of the imino component, and the amine nitrogen bonded to an electron-donating substituent becomes the heterocyclic nitrogen. This is the first report wherein the impact of substituents in directing the regiocyclization has been explained and the structure conflict resolved by single-crystal X-ray analysis

Synthesis, Biological Evaluation, and Radioiodination of Halogenated <i>closo</i>-Carboranylthymidine Analogues

The synthesis and initial biological evaluation of 3-carboranylthymidine analogues (3CTAs) that are (radio)­halogenated at the <i>closo</i>-carborane cluster are described. Radiohalogenated 3CTAs have the potential to be used in the radiotherapy and imaging of cancer because they may be selectively entrapped in tumor cells through monophosphorylation by human thymidine kinase 1 (hTK1). Two strategies for the synthesis of a ¹²⁷I-labeled form of a specific 3CTA, previously designated as <b>N5</b>, are described: (1) direct iodination of <b>N5</b> with iodine monochloride and aluminum chloride to obtain <b>N5-¹²⁷I</b> and (2) initial monoiodination of <i>o</i>-carborane to 9-iodo-<i>o</i>-carborane followed by its functionalization to <b>N5-¹²⁷I</b>. The former strategy produced <b>N5-¹²⁷I</b> in low yields along with di-, tri-, and tetraiodinated <b>N5</b> as well as decomposition products, whereas the latter method produced only <b>N5-¹²⁷I</b> in high yields. <b>N5-¹²⁷I</b> was subjected to nucleophilic halogen- and isotope-exchange reactions using Na^79/81Br and Na¹²⁵I, respectively, in the presence of Herrmann’s catalyst to obtain <b>N5-^79/81Br</b> and <b>N5-¹²⁵I</b>, respectively. Two intermediate products formed using the second strategy, 1-(<i>tert</i>-butyldimethylsilyl)-9-iodo-<i>o</i>-carborane and 1-(<i>tert</i>-butyldimethylsilyl)-12-iodo-<i>o</i>-carborane, were subjected to X-ray diffraction studies to confirm that substitution at a single carbon atom of 9-iodo-<i>o</i>-carborane resulted in the formation of two structural isomers. To the best of our knowledge, this is the first report of halogen- and isotope-exchange reactions of B-halocarboranes that have been conjugated to a complex biomolecule. Human TK1 phosphorylation rates of <b>N5</b>, <b>N5-¹²⁷I</b>, and <b>N5-^79/81Br</b> ranged from 38.0% to 29.6% relative to that of thymidine, the endogenous hTK1 substrate. The in vitro uptake of <b>N5</b>, <b>N5-¹²⁷I</b>, and <b>N5-^79/81Br</b> in L929 TK1­(+) cells was 2.0, 1.8, and 1.4 times greater than that in L929 TK1(−) cells