Electroosmotic flow in channels with step changes in zeta potential and cross section

We consider the effects that step changes in zeta potential and cross section have on electroosmosis in long-and-narrow channels with arbitrary cross-sectional shapes. The Stokes equation of flow is solved analytically utilizing the thin Debye layer approximation to provide effective slip velocities on the channel walls. The effects of channel dimensions, surface potentials, applied pressure drop, and applied voltage are discussed. One anecdotal case, a two-region rectangular channel, is presented to illustrate the solution. The flow in each region is a combination of a uniform electroosmotic flow and a nonuniform pressure-driven flow. The electroosmotic pumping causes the pressure gradient in each region to adjust so that the flow rate is the same in each region and the overall applied pressure drop is met, resulting in convex velocity profiles in some regions and concave velocity profiles in other regions. By appropriate choice of the applied pressure drop, flat velocity profiles may be achieved in one or more regions.     

Determination of erythrocyte deformability and its correlation to cellular ATP release using microbore tubing with diameters that approximate resistance vessels in vivo

A novel method is described for measuring the deformability of red blood cells (RBCs) in tubing whose diameters approximate forces encountered in vivo. Here, RBCs from rabbits are loaded into a 50 cm section of 75 microm id microbore tubing and connected to a syringe pump. This section of tubing is then connected to a 15 cm section of 25 microm id tubing. As buffer is pumped through the flow system, the RBCs are evacuated from both sections of tubing. However, the inability of the RBCs to move freely through the 25 mirom id section of tubing results in a buildup of cells at the inlet of this portion of tubing. The continued force output by the syringe pump results in a deformation of the RBCs until all of the cells are eventually evacuated from the flow system. It was found that a measurement of the time required to reach half of the maximum pressure (1/2 P(max)) may be used as an indicator of the RBC deformability. For a given sample, a simple buffer results in less time to reach 1/2 P(max) (6.9 +/- 0.2 s) than deformable RBCs (21.6 +/- 0.8 s). To verify that the increased amount of time to reach 1/2 P(max) is indeed due to the RBCs, various hematocrits of an RBC sample were investigated and, as expected, it was found that a 12% RBC hematocrit had a higher 1/2 P(max) value (26.0 s +/- 2.2 s) when compared to a 7% hematocrit (19.1 +/- 0.3 s). In addition, RBCs chemically stiffened with glutaraldehyde were shown to be 25% less deformable than normal RBCs. Finally, a study was performed to examine the relationship between RBC deformability and ATP release and it was found that ATP release increased as a function of RBC deformability. This method greatly simplifies deformability measurements, employing only a syringe pump and microbore tubing, and may lead to a more complete understanding of the physiological significance of erythrocyte deformability.     

Trimethylsilylethynyl ketones as surrogates for ethynyl ketones in the double Michael reaction

Trimethylsilylethynyl ketones can be desilylated in the presence of a tethered carbon diacid and induced to undergo a double Michael reaction in situ. The trimethylsilylethynyl ketones can serve as surrogates of ethynyl ketones that are difficult to prepare or isolate.     

Organic-inorganic hybrid materials: hydrothermal syntheses and structural characterization of bimetallic organophosphonate oxides of the type Mo/Cu/O/RPO(3)(2-)/organoimine

The hydrothermal reactions of a Cu(II) starting material, a molybdate source, 2,2'-bipyridine or terpyridine, and the appropriate alkyldiphosphonate ligand yield two series of bimetallic organophosphonate hybrid materials of the general types [Cu(n)(bpy)(m)Mo(x)O(y)(H(2)O)(p)[O(3)P(CH(2))(n)PO(3)](z)] and [Cu(n)(terpy)(m)Mo(x)O(y)(H(2)O)(p)[O(3)P(CH(2))(n)PO(3)](z)]. The bipyridyl series includes the one-dimensional materials [Cu(bpy)(MoO(2))(H(2)O)(O(3)PCH(2)PO(3))] (1) and [[Cu(bpy)(2)][Cu(bpy)(H(2)O)](Mo(5)O(15))(O(3)PCH(2)CH(2)CH(2)CH(2)PO(3))].H(2)O (5.H(2)O) and the two-dimensional hybrids [Cu(bpy)(Mo(2)O(5))(H(2)O)(O(3)PCH(2)PO(3))].H(2)O (2.H(2)O), [[Cu(bpy)](2)(Mo(4)O(12))(H(2)O)(2)(O(3)PCH(2)CH(2)PO(3))].2H(2)O (3.2H(2)O), and [Cu(bpy)(Mo(2)O(5))(O(3)PCH(2)CH(2)CH(2)PO(3))](4). The terpyridyl series is represented by the one-dimensional [[Cu(terpy)(H(2)O)](2)(Mo(5)O(15))(O(3)PCH(2)CH(2)PO(3))].3H(2)O (7.3H(2)O) and the two-dimensional composite materials [Cu(terpy)(Mo(2)O(5))(O(3)PCH(2)PO(3))] (6) and [[Cu(terpy)](2)(Mo(5)O(15))(O(3)PCH(2)CH(2)CH(2)PO(3))] (8). The structures exhibit a variety of molybdate building blocks including isolated [MoO(6)] octahedra in 1, binuclear subunits in 2, 4, and 6, tetranuclear embedded clusters in 3, and the prototypical [Mo(5)O(15)(O(3)PR)(2)](4-) cluster type in 5, 7, and 8. These latter materials exemplify the building block approach to the preparation of extended structures.     

Beyond generative models: superfast traversal,optimization, novelty,exploration and discovery (STONED) algorithm for molecules using SELFIES

Inverse design allows the generation of molecules with desirable physical quantities using property optimization. Deep generative models have recently been applied to tackle inverse design, as they possess the ability to optimize molecular properties directly through structure modification using gradients. While the ability to carry out direct property optimizations is promising, the use of generative deep learning models to solve practical problems requires large amounts of data and is very time-consuming. In this work, we propose STONED – a simple and efficient algorithm to perform interpolation and exploration in the chemical space, comparable to deep generative models. STONED bypasses the need for large amounts of data and training times by using string modifications in the SELFIES molecular representation. First, we achieve non-trivial performance on typical benchmarks for generative models without any training. Additionally, we demonstrate applications in high-throughput virtual screening for the design of drugs, photovoltaics, and the construction of chemical paths, allowing for both property and structure-based interpolation in the chemical space. Overall, we anticipate our results to be a stepping stone for developing more sophisticated inverse design models and benchmarking tools, ultimately helping generative models achieve wider adoption.

Interpolation and exploration within the chemical space for inverse design.     

Diverse evolution of [[Ph(2)P(CH(2))(n)PPh(2)]Pt(mu-S)(2)Pt[Ph(2)P(CH(2))(n)PPh(2)]] (n = 2, 3) metalloligands in CH(2)Cl(2)

The nucleophilicity of the [Pt(2)S(2)] core in [[Ph(2)P(CH(2))(n)PPh(2)]Pt(mu-S)(2)Pt[Ph(2)P(CH(2))(n)PPh(2)]] (n = 3, dppp (1); n = 2, dppe (2)) metalloligands toward the CH(2)Cl(2) solvent has been thoroughly studied. Complex 1, which has been obtained and characterized by X-ray diffraction, is structurally related to 2 and consists of dinuclear molecules with a hinged [Pt(2)S(2)] central ring. The reaction of 1 and 2 with CH(2)Cl(2) has been followed by means of (31)P, (1)H, and (13)C NMR, electrospray ionization mass spectrometry, and X-ray data. Although both reactions proceed at different rates, the first steps are common and lead to a mixture of the corresponding mononuclear complexes [Pt[Ph(2)P(CH(2))(n)PPh(2)](S(2)CH(2))], n = 3 (7), 2 (8), and [Pt[Ph(2)P(CH(2))(n)PPh(2)]Cl(2)], n = 3 (9), 2 (10). Theoretical calculations give support to the proposed pathway for the disintegration process of the [Pt(2)S(2)] ring. Only in the case of 1, the reaction proceeds further yielding [Pt(2)(dppp)(2)[mu-(SCH(2)SCH(2)S)-S,S']]Cl(2) (11). To confirm the sequence of the reactions leading from 1 and 2 to the final products 9 and 11 or 8 and 10, respectively, complexes 7, 8, and 11 have been synthesized and structurally characterized. Additional experiments have allowed elucidation of the reaction mechanism involved from 7 to 11, and thus, the origin of the CH(2) groups that participate in the expansion of the (SCH(2)S)(2-) ligand in 7 to afford the bridging (SCH(2)SCH(2)S)(2-) ligand in 11 has been established. The X-ray structure of 11 is totally unprecedented and consists of a hinged [(dppp)Pt(mu-S)(2)Pt(dppp)] core capped by a CH(2)SCH(2) fragment.     

Self-assembly of tetrahedral and trigonal antiprismatic clusters [Fe4(L4)4] and [Fe6(L5)6] on the basis of trigonal tris-bidentate chelators

In a one-pot reaction, the tetranuclear iron chelate complex [Fe4(L4)4] 6 was generated from benzene-1,3,5-tricarboxylic acid trichloride (4), bis-tert-butyl malonate (5a), methyllithium, and iron(II) dichloride under aerobic conditions. Alternatively, hexanuclear iron chelate complex [Fe(L5)6] 7 was formed starting from bis-para-tolyl malonate (5b) by employing identical reaction conditions to those applied for the synthesis of 6. The clusters 6 and 7 are present as racemic mixtures of homoconfigurational (delta,delta,delta,delta)/(lambda,lambda,lambda,lambda)-fac or (delta,delta,delta,delta,delta,delta)/(lambda,lambda,lambda,lambda,lambda,lambda)-fac stereoisomers. The structures of 6 and 7 were unequivocally resolved by single-crystal X-ray analyses. The all-iron(III) character of 6 and 7 was determined by M?ssbauer spectroscopy.     

High acidity of polycyano azatriquinanes—theoretical prediction by the DFT calculations

It is shown by the B3LYP/6-311+G(2d,p)//B3LYP/6-31G(d) calculations that the hexacyano derivative of aza-acepentalene is an extremely powerful superacid both in the gas phase and in DMSO as evidenced by the ΔH_acid = 255.1  kcal mol⁻¹ and pK_a (DMSO) = −26.5. Its synthesis is strongly recommended, in particular, since the related conjugate base hexachloro aza-acepentalenide anion was prepared recently.     

Selective benzylic lithiation of N-Boc-2-phenylpiperidine and pyrrolidine: expedient synthesis of a 2,2-disubstituted piperidine NK1 antagonist

Unlike the lithiation of N-Boc-2-alkylpiperidines, which occurs at the 6-position, N-Boc-2-phenylpiperidine and N-Boc-2-phenylpyrrolidine can be lithiated exclusively at the 2-position. The tertiary carbanions can be trapped with a variety of electrophiles. This chemistry was used for the synthesis of a potent NK₁ ligand (K_i = 0.3 nM). The bioactive configuration at the piperidine quaternary center was determined by X-ray analysis to be (S).