Counterion Selectivity Research Articles

Rationalizing Counterion Selection for the Development of Lipophilic Salts: A Case Study with Venetoclax.

The use of lipid-based formulations (LBFs) can be hindered by low dose loading due to solubility limitations of candidate drugs in lipid vehicles. Formation of lipophilic salts through pairing these drugs with a lipophilic counterion has been demonstrated as a potential means to enhance dose loading in LBFs. This study investigated the screening of appropriate counterions to form lipophilic salts of the BCS class IV drug venetoclax. The physical properties, lipid solubility, and in vitro performance of the salts were analyzed. This study illustrated the versatility of alkyl sulfates and sulfonates as suitable counterions in lipophilic salt synthesis with up to ∼9-fold higher solubility in medium- and long-chain LBFs when compared to that of the free base form of venetoclax. All salts formulated as LBFs displayed superior in vitro performance when compared to the free base form of the drug due to the higher initial drug loadings in LBFs and increased affinity for colloidal species. Further, in vitro studies confirmed that venetoclax lipophilic salt forms using alkyl chain counterions demonstrated comparable in vitro performance to venetoclax docusate, thus reducing the potential for laxative effects related to docusate administration. High levels of the initial dose loading of venetoclax lipophilic salts were retained in a molecularly dispersed state during dispersion and digestion of the formulation, while also demonstrating increased levels of saturation in biorelevant media. The findings of this study suggest that alkyl chain sulfates and sulfonates can act as a suitable alternative counterion to docusate, facilitating the selection of counterions that can unlock the potential to formulate venetoclax as an LBF.

Sustainable Lithium Recovery from Hypersaline Salt-Lakes by Selective Electrodialysis: Transport and Thermodynamics.

Evaporative technology for lithium mining from salt-lakes exacerbates freshwater scarcity and wetland destruction, and suffers from protracted production cycles. Electrodialysis (ED) offers an environmentally benign alternative for continuous lithium extraction and is amenable to renewable energy usage. Salt-lake brines, however, are hypersaline multicomponent mixtures, and the impact of the complex brine-membrane interactions remains poorly understood. Here, we quantify the influence of the solution composition, salinity, and acidity on the counterion selectivity and thermodynamic efficiency of electrodialysis, leveraging 1250 original measurements with salt-lake brines that span four feed salinities, three pH levels, and five current densities. Our experiments reveal that commonly used binary cation solutions, which neglect Na+ and K+ transport, may overestimate the Li+/Mg2+ selectivity by 250% and underpredict the specific energy consumption (SEC) by a factor of 54.8. As a result of the hypersaline conditions, exposure to salt-lake brine weakens the efficacy of Donnan exclusion, amplifying Mg2+ leakage. Higher current densities enhance the Donnan potential across the solution-membrane interface and ameliorate the selectivity degradation with hypersaline brines. However, a steep trade-off between counterion selectivity and thermodynamic efficiency governs ED's performance: a 6.25 times enhancement in Li+/Mg2+ selectivity is accompanied by a 71.6% increase in the SEC. Lastly, our analysis suggests that an industrial-scale ED module can meet existing salt-lake production capacities, while being powered by a photovoltaic farm that utilizes <1% of the salt-flat area.

PyConSolv: A Python Package for Conformer Generation of (Metal-Containing) Systems in Explicit Solvent.

We introduce PyConSolv, a freely available Python package that automates the generation of conformers of metal- and nonmetal-containing complexes in explicit solvent, through classical molecular dynamics simulations. Using a streamlined workflow and interfacing with widely used computational chemistry software, PyConSolv is an all-in-one tool for the generation of conformers in any solvent. Input requirements are minimal; only the geometry of the structure and the desired solvent in xyz (XMOL) format are needed. The package can also account for charged systems, by including arbitrary counterions in the simulation. A bonded model parametrization is performed automatically, utilizing AmberTools, ORCA, and Multiwfn software packages. PyConSolv provides a selection of preparametrized solvents and counterions for use in classical molecular dynamics simulations. We show the applicability of our package on a number of (transition-metal-containing) systems. The software is provided open source and free of charge.

Cation Exchange Membranes and Process Optimizations in Electrodialysis for Selective Metal Separation: A Review.

The selective separation of metal species from various sources is highly desirable in applications such as hydrometallurgy, water treatment, and energy production but also challenging. Monovalent cation exchange membranes (CEMs) show a great potential to selectively separate one metal ion over others of the same or different valences from various effluents in electrodialysis. Selectivity among metal cations is influenced by both the inherent properties of membranes and the design and operating conditions of the electrodialysis process. The research progress and recent advances in membrane development and the implication of the electrodialysis systems on counter-ion selectivity are extensively reviewed in this work, focusing on both structure-property relationships of CEM materials and influences of process conditions and mass transport characteristics of target ions. Key membrane properties, such as charge density, water uptake, and polymer morphology, and strategies for enhancing ion selectivity are discussed. The implications of the boundary layer at the membrane surface are elucidated, where differences in the mass transport of ions at interfaces can be exploited to manipulate the transport ratio of competing counter-ions. Based on the progress, possible future R&D directions are also proposed.

Computational and Experimental Screening Approaches to Aripiprazole Salt Crystallization.

The screening of multicomponent crystal system (MCC) is a key method for improving physicochemical properties of active pharmaceutical ingredients (APIs). The challenges associated with experimental salt screening include a large number of potential counterions and solvent systems and tendency to undergo disproportionation to produce free form during crystallization. These challenges may be mitigated by a combination of experimental and computational approaches to salt screening. The goal of this study is to evaluate performance of the counterion screening methods and propose and validate novel approaches to virtual solvent screening for MCC crystallization. The actual performance of the ΔpKa > 3 rule for counterion selection was validated using multiple screenings reports. Novel computational models for virtual solvent screening to avoid MCC incongruent crystallization were proposed. Using the ΔpKa rule, 10 acid counterions were selected for experimental aripiprazole (APZ) salt screening using 10 organic solvents. The experimental results were used to validate the proposed novel virtual solvent screen models. Experimental APZ salt screening resulted in a total of eight MCCs which included glucuronate, mesylate, oxalate, tartrate, salicylate and mandelate. The new model to virtually screen solvents provided a general agreement with APZ experimental findings in terms of selecting the optimal solvent for MCC crystallization. The rational selection of counterions and organic solvents for MCC crystallization was presented using combined novel computational model as well as experimental studies. The current virtual solvent screen model was successfully implemented and validated which can be easily applied to newly discovered APIs.

Impact of the Donnan electrolytes on selectivity of cation exchange membranes evaluated via the ionic membrane conductivity

The selectivity of an ion exchange membrane (IEM) is an essential property in related electro-chemical separation and clean production processes. The impact of the Donnan electrolytes on the counter-ion selectivity of three representative cation exchange membranes (CEMs) evaluated via the ionic membrane conductivity is systematically studied in the mixed MgSO4/Na2SO4 and H2SO4/Na2SO4 electrolytes, over an external total sulfate concentration range of 0.1 ∼ 1.0 M. The counter-ions selectivity is decoupled into the partitioning selectivity coefficient (Kji) and the mobility ratio (uim/ujm), both of which are related to the CEM conductivity. If the Donnan electrolytes conductivity is excluded, for the heterogeneous CEM (3361BW), the selectivity calculated from the ion-exchanged conductivity (κE) can be perfectly matched with the electrodialysis (ED) results under a lower external sulfate concentration (0.1 M). The Mg2+/Na+ selectivity values of two homogeneous CEMs (Nafion117 and CSE) obtained from the nonlinear correlation method derived from the Kohlrausch's law (σ) are closer to the ED values, while the linear correlation approaches are more suitable at the presence of H2SO4. By analyzing the variation of Kji and uim/ujm with the κE separately, the main reason for the variation of the Mg2+/Na+ selectivity for these three CEMs, when the external electrolytes concentration increases, is the different equilibrium partitioning selectivity coefficients (KNa+Mg2+) between the membrane and the solution. On the contrary, the H+ ions transport much faster than the Na+ ions within the CEMs, and it is the change of this mobility ratio that causes the different H+/Na+ selectivity results. This work not only expands the application of the proposed conductivity method, but also provides a new perspective for studying the sorption and transport mechanism of ions in electro-chemical processes based on IEMs.

Assessment of hydrophobic-ion paired insulin incorporated SMEDDS for the treatment of diabetes mellitus

To overcome the low oral bioavailability of insulin, we hypothesized that the insulin-hydrophobic ion pairing (HIP) complex incorporated self-microemulsifying drug delivery system (SMEDDS) would be beneficial. In the present study, an oral insulin delivery system was developed and estimated using the HIP technique and SMEDDS. Further insulin-HIP complexes were characterized using various spectroscopical techniques. Additionally, insulin-HIP complexes were subjected to analysis of complexes' conformational stability in the real physiological solution using computational approaches. On the other hand, in vitro, and in vivo studies were carried out to investigate the permeability and hypoglycemic effect. Subsequently, in an in vitro non-everted gut sac study, the apparent permeability coefficient (Papp) was approximately 8-fold higher in the colon than in the jejunum, and the HIP-incorporated SMEDDS showed an approximately 3-fold higher Papp value than the insulin solution. The hypoglycemic effect after in situ colon instillation, the HIP complex between insulin and sodium docusate-incorporated SMEDDS showed a pharmacological availability of 2.52 ± 0.33 % compared to the subcutaneously administered insulin solution. Thus, based on these outcomes, it can be concluded that the selection of appropriate counterions is important in developing HIP-incorporated SMEDDS, wherein this system shows promise as a tool for oral peptide delivery systems.

Enhanced electroosmotic flow, conductance and ion selectivity of a viscoplastic fluid in a hydrophobic cylindrical pore

We have studied the electroosmotic flow (EOF) of a non-Newtonian viscoplastic fluid, modeled as a Herschel-Bulkley (H-B) fluid, through a single hydrophobic nanopore in a uniformly charged solid hydrophobic membrane separating two identical reservoirs. An interfacial slip velocity develops when the viscoplastic fluid is strained over a hydrophobic surface. It is well established in the context of Newtonian fluid that the interfacial slip at the charged surface augments the EOF. For the viscoplastic fluid, the EOF depends on the fluid behavioral index and the yield stress. We have illustrated the impact of the interfacial slip on the EOF, conductance and ion selectivity of the cylindrical nanopore at different yield stresses for both the shear thinning and the shear thickening cases of the H-B fluid. The slip velocity, characterized by the slip length, enhances the average flow and conductance of the pore and this impact is pronounced for the shear thinning case. The unyielded zone, which develops along the central line of the pore, contracts as the slip length is increased. The ion concentration polarization enhances for the shear thinning fluid, however, the slip length creates a marginal increment. The counterion selectivity of the pore is found to be significant for the Newtonian case as compared to the non-Newtonian fluid and the velocity slip enhances the ion selectivity further. We have determined an analytic solution for the EOF of a power-law fluid in a long hydrophobic tube. Our computed solution for the case of a long tube effectively coincides with this analytic solution. An increment in the pore length reduces its conductance but enhances the ion selectivity. The increment of the average EOF for the hydrophobic pore as compared to the no-slip case grows as the pore length is increased.

Combining Manning's theory and the ionic conductivity experimental approach to characterize selectivity of cation exchange membranes

The transport selectivity of different cations through cation exchange membranes (CEMs) could be estimated with the partitioning selectivity factor (Kji) and the cation mobility ratio in the membrane (uim/ujm), which in turn can be related to corresponding membrane conductivity and dimensional swelling ratio data [Journal of Membrane Science, 2020, 597, 117645]. This method has been validated in two hydrocarbon polymer-based CEMs, and the obtained K+/Na+ selectivity equals to the one obtained with conventional electrodialysis (ED) method. However, the K+/Na+ selectivity of perfluorosulfonic acid (PFSA) membranes, and the bi-/monovalent cation (Mg2+/Na+) selectivity of all three types of CEMs estimated with this ionic conductivity experimental approach deviate noticeably from corresponding values obtained with ED. In this work, it is proved that this deviation is partly due to the simplification of cation activity coefficients in the membrane. Here, the cation activity coefficients in three types of CEMs are calculated according to Manning's counter-ion condensation model. In this model, the Manning parameter (ξ) characterizing the dimensionless linear charge density is determined by the average distance between two adjacent fixed sulfonate groups (b) and the permittivity of hydrated membranes (ε). In hydrocarbon polymer-based CEMs, the average distance between fixed sulfonate groups can be estimated by assuming homogeneous distribution of the fixed groups, while in PFSA membranes three representative structure models are employed to estimate this average distance. After accounting for the cation activity coefficients in the membrane, the Mg2+/Na+ cation transport selectivity obtained with the ionic conductivity experimental approach gets closer to, but is still smaller than the selectivity obtained with the ED method. This work shows the importance of cation activity coefficients in the membrane phase in interpreting the membrane transport properties, and complements the proposed conductivity approach to characterize the counter-ion selectivity of ion exchange membranes.

Ion selectivity by charged spherical cavities and investigation of intersection point for average cavity density versus electric potential (a DFT study)

Ion separation and ion selectivity inside spherical cavities are studied within the framework of the density functional theory. Results show that, at lower electric potentials and depending on cavity size, counter ions accumulate at the wall to form a shell around the co ions that prefer to aggregate in the middle of the cavity. This gives rise to the formation of separated phases of co ions and counter ions inside the spherical cavity. Depending on cavity size, these phases convert to a nearly single phase of counter ions with increasing electric potential. In this situation, small spherical cavities could be exploited as a counter ion selector tool. Our study also shows that counter ion selectivity readily occurs at lower, rather than higher, concentrations of electrolytes. For electrolytes with monovalent co ions, the (+1: −1) electrolytes exhibit a better selectivity than the (+1: −2) ones at low electric potentials. Also the selective counter ion adsorption occurs at lower electric potential when the difference between size of counter ions and co ions becomes larger. The observed selectivity is the result of confinement effect, electrostatic interaction, and excluded volume. Our study of the average cavity density versus electric potential shows an intersection for different plots related to cavities of different sizes. This intersection point reveals two different behaviors of average cavity density with cavity size on the two sides of the intersection point. In other words, average cavity density increases (decreases) with cavity size for those electric potentials which are lower (higher) than that of the intersection point but it becomes independent of cavity size for the electric potential of the intersection point.

Ion mobility and partition determine the counter-ion selectivity of ion exchange membranes

Ion (perm)selectivity and conductivity are the two essential properties of an ion exchange membrane, yet no quantitative relation between them has been suggested. Here, the selectivity between two different counter-ions is correlated to the membrane conductivity. We show that the counter-ion selectivity measured by conventional electrodialysis (ED) can be expressed by the product of: (a) the mobility ratio between two different counter-ions in the membrane and (b) their partition coefficient between the solution and the membrane. This is reminiscent of the classical solution-diffusion model. Via the counter-ion mobility in the membrane, the selectivity could be simply expressed with the membrane conductivity and dimensional swelling degree. This correlation is validated experimentally for the ion selectivity of K+/Na+ in two commercial hydrocarbon-based cation exchange membranes (CEMs). For K+/Na+ in a perfluorosulfonic CEM, and for Mg2+/Na+ in all the three types of CEMs, the correlation could predict the counter-ion partition very well; but there is an underestimation of the K+/Na+ and Mg2+/Na+ mobility ratios. This work offers a convenient method to decouple experimentally the effect of partition and mobility in controlling the membrane selectivity, and also proposes a new perspective to study the selectivity as well as conductivity of ion exchange membranes.

Elucidating conductivity-permselectivity tradeoffs in electrodialysis and reverse electrodialysis by structure-property analysis of ion-exchange membranes

Ion-exchange membranes (IEMs) are used in environmental and energy technologies of electrodialysis (ED) desalination and reverse electrodialysis (RED) power generation, respectively. Recent studies reported empirical evidence that the conductivity and permselectivity of IEMs are bound by a tradeoff relationship, where an increase in ionic conductivity is accompanied by a decrease in counterion selectivity over co-ion. A fundamental understanding of this conductivity-permselectivity tradeoff is principal to inform membrane development. This study presents an IEM transport model to analytically relate conductivity and permselectivity to intrinsic membrane chemical and structural properties. The model employs the Nernst-Planck transport framework and incorporates counterion condensation theory to simulate the performance of IEMs in a range of ED and RED operations. The analysis revealed the mechanism for the tradeoff induced by bulk solution concentration: a higher salinity suppresses IEM charge-exclusion, thus lowering permselectivity, but elevates mobile ion concentration within the membrane matrix to improve conductivity. As such, IEM applications are practically confined to sub-seawater salinities, i.e., RED using hypersaline streams will not be efficient. In another tradeoff driven by IEM water sorption, increasing membrane swelling enhances effective ion diffusivity to raise conductivity, but diminishes permselectivity due to dilution of fixed charges. The transport model indicates that increasing membrane ion-exchange capacity and reducing thickness can yield highly selective and conductive IEMs.

Probing Magnetic-Exchange Coupling in Supramolecular Squares Based on Reducible Tetrazine-Derived Ligands.

Reducible 3,6-bis(3,5-dimethyl-pyrazolyl)1,2,4,5-tetrazine was employed to isolate supramolecular air-stable [Co4 ] and [Zn4 ] squares, which were achieved via careful selection of counterions rather than the use of reducing agents. Magnetic susceptibility studies revealed a strong radical-CoII exchange coupling (Jrad-Co /hc=-118 cm-1 , -2J formalism) with a spin ground state of ST =4, whereas the unreduced analogue revealed negligible coupling between the Co centers (JCo-Co /hc=-0.64 cm-1 ). Radical-radical coupling was also probed in the [Zn4 ] congener, which led to Jrad-rad /hc=-15.9(5) cm-1 . These results highlight the versatile air-stable coordination chemistry of tetrazine and the importance of exploiting easily reducible delocalized radical to promote strong exchange coupling between spin carriers.

In Situ Salification in Polar Solvents: a Paradigm for Enabling Drug Delivery of Weakly Ionic Drugs as Amorphous Solid Dispersion.

Solubility challenge for a poorly water-soluble drug gets further intensified when it is weakly ionic because the most common solubility enhancement technique, salt formation, becomes less feasible. Salt screening for such drugs often concludes with either a difficult to crystalize salt or an unstable salt, leading the scientists to explore other solubility enhancement technique like amorphous solid dispersions which is comparatively costlier, time-consuming and may require use of hazardous organic solvents. Present study evaluated in situ salification in polar protic solvents for dissolving poorly water-soluble drug Itraconazole which is weakly ionic and not very amenable to formation of stable inorganic salts. Through systematic selection of solvents, counterions and polymers, an amorphous solid dispersion of drug salt was obtained. In vitro characterizations with polarized light microscopy (PLM), modulated differential scanning calorimetry (mDSC), Fourier transform infrared spectroscopy (FTIR) and X-ray powder diffraction (XRD) confirmed the physical and chemical stability of the amorphous solid dispersion. In vivo pharmacokinetic study showed that the drug salt amorphous solid dispersion achieved 45 times higher plasma exposure compared to crystalline drug. This study provides one of the first data sets for the hypothesis that in situ drug salts can be utilized for manufacturing amorphous solid dispersions of weakly ionic drugs and leverages the solubility advantage of salts and amorphous state.

Controlling the Intermediate Structure of an Ionic Liquid for f-Block Element Separations.

Recent research has revealed molecular structure beyond the inner coordination sphere is essential in defining the performance of separation processes; nevertheless, such structure remains largely unexplored. Here we apply small-angle neutron scattering (SANS) and X-ray absorption fine structure (XAFS) spectroscopy to investigate the structure of an ionic liquid system studied for f-block element separations. SANS data reveal dramatic changes in the ionic liquid microstructure (∼150 Å) which we demonstrate can be controlled by judicious selection of counterion. Mesoscale structural features (>500 Å) are also observed as a function of metal concentration. XAFS analysis supports formation of extended aggregate structures, similar to those observed in traditional solvent extraction processes, and suggests additional parallels may be drawn from further study. Achieving precise tunability over the intermediate features is an important development in controlling mesoscale structure and realizing advanced new forms of soft matter.

Counter-ion binding and mobility in the presence of hydrophobic polyions – combining molecular dynamics simulations and NMR

Counter-ion binding and mobility in aqueous solutions of partially hydrophobic ionene oligoions is studied here by a combination of all-atomic molecular dynamics (MD) simulations and NMR (19F and 81Br nuclei) measurements. We present results for 12, 12–ionenes in the presence of different halide ions (F−, Cl−, Br− and I−), as well as their mixtures; the latter allowing us to probe counter-ion selectivity of these oligoions. We consolidate both structural and dynamic information, in particular simulated radial distribution functions and average residence times of counter-ions in the vicinity of ionenes and NMR data in the form of counter-ion chemical shift and self-diffusion coefficients. On one hand, previously reported enthalpy of dilution and mixing measurements show a reverse counter-ion sequence for 12, 12–ionenes with respect to their less hydrophobic 3, 3– and 6, 6– analogues. On the other hand, the current MD and NMR data, reflecting the counter-ion binding tendencies to the ionene chain, give evidence for the same ordering as that observed by MD for 3, 3–ionenes. This is not seen as a contradiction and can be rationalized on the basis of increasing chain hydrophobicity, which has different consequences for enthalpy and ion-binding. The latter is reflecting free energy changes and as such includes both enthalpic and entropic contributions.

Carbon Coated Metal Nanoparticles for Electrocatalysis

To promote the performance of nanoparticle electrocatalysts, a facile hydrothermal method is developed to generate core–shell nanocomposites with a metal catalyst core and a carbon shell. In this method, glucose serves as the reducing agent and carbon precursor while cetyltrimethylammonium surfactants serve as both pore structure-directing agents and nanoparticle capping agent. The accessibility of the metal catalyst core was examined by gas-phase ethylene hydrogenation and the electrocatalytic activity was tested by formic acid oxidation (FOR). The selection of halide counter ions used during the synthesis was found to be critical. The optimized sample of Pd-carbon nanocomposite exhibits a FOR current density of 2.55 mA/cm2, which is higher than that of un-coated Pd nanoparticles with no support (0.89 mA/cm2) and with carbon nanotube support (1.08 mA/cm2).

Influence of the pendant arm, halide, and solvent on high-efficient-tuning [1 + 1] and [2 + 2] schiff-base macrocyclic complexes via a zinc-ion template.

A series of pendant-armed Schiff-base macrocyclic complexes 1-7 have been prepared by the condensation between extended dialdehydes with pendant arms (H2hpdd/H2pdd) and 1,3-propanediamine in the presence of ZnX2 (X = Cl, Br, I), where 18-membered [1 + 1] mononuclear and 36-membered [2 + 2] half-fold trinuclear macrocyclic zinc(II) complexes are yielded. Three experimental variables, i.e., the pendant arm, halide, and solvent, are found to influence the organization of final macrocyclic complexes, in addition to the conventional metal-ion template effect promoting reversible formation and cleavage of Schiff-base imine bonds. It is noted that all of the reactions produce singular macrocyclic complexes in high yields if the experimental variables are fixed, and the selection of different pendant arms and halide counterions will generate different [1 + 1] mononuclear and [2 + 2] trinuclear macrocyclic zinc(II) complexes. More interestingly, [1 + 1] and [2 + 2] macrocyclic zinc(II) complexes 2 and 3 can be produced in methanol and ethanol, respectively, in the case of the reaction between ZnBr2, H2pdd, and 1,3-propanediamine. Further experiments reveal that red solid 2 and yellow-green solid 3 can be transformed to each other just by altering the type of solvent, and this tuning is complete and reversible.

Controlled synthesis of micro/nanostructured CuO anodes for lithium-ion batteries

Three different morphology controlled copper oxide materials (porous microspheres, flower-like, and thorn-like CuO) were prepared by facile and environmentally friendly processes, which were further investigated for their electrochemical properties and performance at lithium-ion battery anodes. CuO microspheres were prepared by simply solution chemistry, whereas flower-like and thorn-like CuO structures were prepared hydrothermally, with the structural transformations arising due to selection of chloride or sulfate counter ions in the precursor salts, respectively. After a 400°C heat treatment in air, the morphology controlled materials demonstrated excellent phase purity as indicated by X-ray diffraction (XRD), and we propose a growth mechanism for the various materials based on systematic investigation of the structure and properties of the intermediate species. The electrochemical and lithium-ion battery performance employing the shape controlled CuO materials was investigated, allowing for elucidation of the synthesis–structure–performance correlations of CuO-based anodes. The performance of lithium-ion batteries was found to be highly dependent on the CuO morphology. The CuO microspheres exhibit a superior electrochemical performance to the other two CuO samples in terms of cycle capacity and rate performance, indicating a viable strategy to prepare next-generation lithium-ion battery systems with improved storage capacities.

Weak polyelectrolytes in the presence of counterion condensation with ions of variable size and polarizability

.Light scattering and viscometric measurements on weak polyelectrolytes show two important aspects of counterion condensation, namely, non-monotonic variation in the polyelectrolyte size with the increase in the electrostatic strength, and, monovalent counterion selectivity in determining the nature of collapse transition at high electrostatic strengths. Here, we present a self-consistent variational theory for weak polyelectrolytes which includes the effects of the polarizability of monovalent counterions. Our theory reproduces several experimental findings including non-monotonic conformational size with the variation in the electrostatic strength and a shift from a continuous to a discontinuous collapse transition with the increase in the dipole strength of condensed ions. At low dipole strength and high electrostatic strength, our theory predicts a series of solvent quality driven size transitions spanning the re-entrant poor, theta and good solvent regimes. At high dipole strength, the size remains that of a compact globule independent of solvent quality. The dipole strength of the ion-pair formed due to counterion condensation, which depends on the size and polarizability of the monovalent counterions, is found to be an important molecular parameter in determining the nature of collapse transition, and the size of the collapsed state at high electrostatic strength.