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1. A reliable algorithm for calculating stoichiometry parameters in the hard modeling of spectrophotometric titration data

   https://doi.org/10.1002/cem.3409  

   Kazmierczak, Nathanael_P; Chew, Joyce_A; Vander_Griend, Douglas_A (May 2022, Journal of Chemometrics)

   Abstract Computation of binding constants from spectrophotometric titration data is a very popular application of chemometric hard modeling. However, the calculated values are misleading if the correct binding model is not used. Given that many supramolecular systems of interest feature unknown speciation, a priori determination of binding stoichiometry constitutes an important unsolved problem in chemometrics. We present a new and reliable algorithm for accomplishing this task, implemented using a hybrid particle swarm optimization technique. Simultaneous optimization of stoichiometry ratios and binding constants allows the optimal binding model to be calculated in just a few minutes for systems with up to four reactions. Simulated data studies demonstrate that the algorithm finds the correct stoichiometry with up to nine reactions in the absence of noise, including accurately determining species with unusual stoichiometry, such as H₂G₅. Application to four experimental datasets shows the algorithm is robust to experimental errors for a variety of chemical systems and binding models. This algorithm will facilitate the discovery of complex binding models, increase efficiency in titration analysis, and avert incorrect stoichiometry models, thereby improving the reliability of binding constant information in spectrophotometric titrations. 

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2. Solution Studies of a Water-Stable, Trivalent Antimony Pnictogen Bonding Anion Receptor with High Binding Affinities for CN ^– , OCN ^– , and OAc ^–

   https://doi.org/10.1021/acs.inorgchem.3c01887  

   Qiu, Jinchun; Bateman, Curt N.; Lu, Shuai; George, Gary C.; Li, Xiaopeng; Gorden, John D.; Vasylevskyi, Serhii; Cozzolino, Anthony F. (August 2023, Inorganic Chemistry)

   The solution phase anion binding behavior of a water-stable bidentate pnictogen bond donor was studied. A modest change in the visible absorption spectrum allowed for the determination of the binding constants. High binding constants were observed with cyanide, cyanate, and acetate, and these were corroborated with density functional theory (DFT) calculations. The receptor could be recovered free from the anion following treatment with methyl triflate, confirming that it remains intact. The tight binding of cyanide and water stability were exploited to use this system as a supramolecular catalyst in a phase-transfer Strecker reaction, further demonstrating the utility of pnictogen bonding as a tool in noncovalent catalysis. 

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3. Expanding reversible chalcogenide binding: supramolecular receptors for the hydroselenide (HSe ⁻ ) anion

   https://doi.org/10.1039/c8sc03968b  

   Fargher, Hazel A.; Lau, Nathanael; Zakharov, Lev N.; Haley, Michael M.; Johnson, Darren W.; Pluth, Michael D. (January 2019, Chemical Science)

   Synthetic supramolecular receptors have been widely used to study reversible solution binding of anions; however, few systems target highly-reactive species. In particular, the hydrochalcogenide anions hydrosulfide (HS − ) and hydroselenide (HSe − ) have been largely overlooked despite their critical roles in biological systems. Herein we present the first example of reversible HSe − binding in two distinct synthetic supramolecular receptors, using hydrogen bonds from N–H and aromatic C–H moieties. The arylethynyl bisurea scaffold 1tBu achieved a binding affinity of 460 ± 50 M −1 for HSe − in 10% DMSO- d 6 /CD 3 CN, whereas the tripodal-based receptor 2CF3 achieved a binding affinity of 290 ± 50 M −1 in CD 3 CN. Association constants were also measured for HS − , Cl − , and Br − , and both receptors favored binding of smaller, more basic anions. These studies contribute to a better understanding of chalcogenide hydrogen bonding and provide insights into further development of probes for the reversible binding, and potential quantification, of HSe − and HS − . 

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4. Asymmetric protonation of glutamate residues drives a preferred transport pathway in EmrE

   https://doi.org/10.1073/pnas.2110790118  

   Li, Jianping; Sae Her, Ampon; Traaseth, Nathaniel J. (October 2021, Proceedings of the National Academy of Sciences)

   EmrE is anEscherichia colimultidrug efflux pump and member of the small multidrug resistance (SMR) family that transports drugs as a homodimer by harnessing energy from the proton motive force. SMR family transporters contain a conserved glutamate residue in transmembrane 1 (Glu14 in EmrE) that is required for binding protons and drugs. Yet the mechanism underlying proton-coupled transport by the two glutamate residues in the dimer remains unresolved. Here, we used NMR spectroscopy to determine acid dissociation constants (pK_a) for wild-type EmrE and heterodimers containing one or two Glu14 residues in the dimer. For wild-type EmrE, we measured chemical shifts of the carboxyl side chain of Glu14 using solid-state NMR in lipid bilayers and obtained unambiguous evidence on the existence of asymmetric protonation states. Subsequent measurements of pK_avalues for heterodimers with a single Glu14 residue showed no significant differences from heterodimers with two Glu14 residues, supporting a model where the two Glu14 residues have independent pK_avalues and are not electrostatically coupled. These insights support a transport pathway with well-defined protonation states in each monomer of the dimer, including a preferred cytoplasmic-facing state where Glu14 is deprotonated in monomer A and protonated in monomer B under pH conditions in the cytoplasm ofE. coli. Our findings also lead to a model, hop-free exchange, which proposes how exchangers with conformation-dependent pK_avalues reduce proton leakage. This model is relevant to the SMR family and transporters comprised of inverted repeat domains. 

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5. Properly handling negative values in the calculation of binding constants by physicochemical modeling of spectroscopic titration data

   https://doi.org/10.1002/cem.3183  

   Kazmierczak, Nathanael_P; Vander_Griend, Douglas_A (August 2019, Journal of Chemometrics)

   Abstract To implement equilibrium hard‐modeling of spectroscopic titration data, the analyst must make a variety of crucial data processing choices that address negative absorbance and molar absorptivity values. The efficacy of three such methodological options is evaluated via high‐throughput Monte Carlo simulations, root‐mean‐square error surface mapping, and two mathematical theorems. Accuracy of the calculated binding constant values constitutes the key figure of merit used to compare different data analysis approaches. First, using singular value decomposition to filter the raw absorbance data prior to modeling often reduces the number of negative values involved but has little effect on the calculated binding constant despite its ability to address spectrometer noise. Second, both truncation of negative molar absorptivity values and the fast nonnegative least squares algorithms are superior to unconstrained regression because they avoid local minima; however, they introduce bias into the calculated binding constants in the presence of negative baseline offsets. Finally, we establish two theorems showing that negative values are best addressed when all the chemical solutions leading to the raw absorbance data are the result of mixing exactly two distinct stock solutions. This allows the raw absorbance data to be shifted up, eliminating negative baseline offsets, without affecting the concentration matrix, residual matrix, or calculated binding constants. Otherwise, the data cannot be safely upshifted. A comprehensive protocol for analyzing experimental absorbance datasets with is included. 

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