Measuring and Leveraging Electrostatic Effects in a Charged Phosphine

<div>Local electric fields have recently been investigated for optimizing reactivity in synthetic systems. However, disentangling the relative contributions of inductive (through-bond) and electrostatic (through-space) effects in molecular systems has been a long-standing challenge. To understand the interplay of these effects and leverage electrostatic influences for enhanced reactivity, we have synthesized a distally charged phosphine, Ph₂PCH₂BF₃⁻, and studied the effect of the charged trifluoroborate group on its donor properties and reactivity. This charged phosphine displays solvent-dependent changes in donor strength as measured by the <i>J</i>_P-Se of the corresponding phosphine selenide. The variation with solvent dielectric illustrates a significant electrostatic component to the donor strength. Computations further support the importance of electrostatic contributions and highlight the effect of charge position and orientation. Finally, this charged group also greatly accelerates C–F oxidative addition reactivity in Ni complexes, experimentally</div><div>verifying recent theoretical predictions. These results show that covalently bound charged functionalities can exert a significant electrostatic influence even under common solution phase reaction conditions.</div>

Measuring and Leveraging Electrostatic Effects in a Charged Phosphine

<div>Local electric fields have recently been investigated for optimizing reactivity in synthetic systems. However, disentangling the relative contributions of inductive (through-bond) and electrostatic (through-space) effects in molecular systems has been a long-standing challenge. To understand the interplay of these effects and leverage electrostatic influences for enhanced reactivity, we have synthesized a distally charged phosphine, Ph₂PCH₂BF₃⁻, and studied the effect of the charged trifluoroborate group on its donor properties and reactivity. This charged phosphine displays solvent-dependent changes in donor strength as measured by the <i>J</i>_P-Se of the corresponding phosphine selenide. The variation with solvent dielectric illustrates a significant electrostatic component to the donor strength. Computations further support the importance of electrostatic contributions and highlight the effect of charge position and orientation. Finally, this charged group also greatly accelerates C–F oxidative addition reactivity in Ni complexes, experimentally</div><div>verifying recent theoretical predictions. These results show that covalently bound charged functionalities can exert a significant electrostatic influence even under common solution phase reaction conditions.</div>

Tinocordiside from Tinospora cordifolia (Giloy) May Curb SARS-CoV-2 Contagion by Disrupting the Electrostatic Interactions between Host ACE2 and Viral S-Protein Receptor Binding Domain

Background: SARS-CoV-2 has been shown to bind the host cell ACE2 receptor through its spike protein receptor binding domain (RBD), required for its entry into the host cells. Objective: We have screened phytocompounds from a medicinal herb, Tinospora cordifolia, for their capacities to interrupt the viral RBD and host ACE2 interactions. Method: We employed molecular docking to screen phytocompounds in T. cordifolia against the ACE2-RBD complex, performed molecular dynamics (MD) simulation, and estimated the electrostatic component of binding free energy. Results: ‘Tinocordiside’ docked very well at the center of the interface of ACE2-RBD complex, and was found to be well stabilized during MD simulation. Tinocordiside incorporation significantly decreased electrostatic component of binding free energies of ACE2-RBD complex (23.5 and 17.10 kcal/mol in the trajectories without or with the ligand, respectively). As the basal rate constant of protein association is in the order of 5, (105 to 106 M-1 S-1 ), there might be no big conformational change or loop reorganization, but involves only local conformational change typically observed in diffusion-controlled association. Taken together, the increase in global flexibility of the complex, clearly indicates the start of unbinding process of the complex. Conclusion: It indicates that such an interruption of electrostatic interactions between the RBD and ACE2, and the increase in global flexibility of the complex, would weaken or block SARS-CoV-2 entry and its subsequent infectivity. We postulate that natural phytochemicals like Tinocordiside could be the viable options for controlling SARS-CoV-2 contagion and its entry into host cells.

Halogen-Bonded BODIPY Frameworks with Tunable Optical Features

The ability to tune optical features of BODIPY materials is essential for their photo-related application. However, it is challenging to efficiently tune the crystal packing of BODIPY derivatives because of their complex nature. In this study, such control of BODIPY supramolecular assemblies was achieved by designing a BODIPY containing a halogen bond (XB) acceptor (–NO2) and donor (I, Br) to mediate halogen bonding interactions. The mono halogenated 2 and 4 was unable to form XB, whereas 3 and 5 formed isostructural mono-coordinate motif 3, 5-I (1D tubular structure) and symmetric bifurcated motif 5-II (1D zig-zag chains structure) via N-O···I,Br XB interactions. The results show that the dispersion and electrostatic component are the major source of 3, 5-I and 5-II XB formations. The XB interaction between –NO2 and X (I, Br) promote singlet-to-triplet intersystem crossing and triplet-to-singlet reverse intersystem crossing due to delocalization of oxygen electrons partially onto the Br and I. Then this interaction leads to unexpected fluorescence enhancement of 5-II. Finally, the indirect optical band gaps of the 3, 5-I and 5-II were able to be tuned in the range of 1.9–2.50 eV via XB driven crystal packings.

Halogen-Bonded BODIPY Frameworks with Tunable Optical Features

The ability to tune optical features of BODIPY materials is essential for their photo-related application. However, it is challenging to efficiently tune the crystal packing of BODIPY derivatives because of their complex nature. In this study, such control of BODIPY supramolecular assemblies was achieved by designing a BODIPY containing a halogen bond (XB) acceptor (–NO2) and donor (I, Br) to mediate halogen bonding interactions. The mono halogenated 2 and 4 was unable to form XB, whereas 3 and 5 formed isostructural mono-coordinate motif 3, 5-I (1D tubular structure) and symmetric bifurcated motif 5-II (1D zig-zag chains structure) via N-O···I,Br XB interactions. The results show that the dispersion and electrostatic component are the major source of 3, 5-I and 5-II XB formations. The XB interaction between –NO2 and X (I, Br) promote singlet-to-triplet intersystem crossing and triplet-to-singlet reverse intersystem crossing due to delocalization of oxygen electrons partially onto the Br and I. Then this interaction leads to unexpected fluorescence enhancement of 5-II. Finally, the indirect optical band gaps of the 3, 5-I and 5-II were able to be tuned in the range of 1.9–2.50 eV via XB driven crystal packings.

Withanone from Withania somnifera May Inhibit Novel Coronavirus (COVID-19) Entry by Disrupting Interactions between Viral S-Protein Receptor Binding Domain and Host ACE2 Receptor

Background Newly emerged COVID-19 has been shown to engage the host cell ACE2 through its spike protein receptor binding domain (RBD). Here we show that natural phytochemical from a medicinal herb, Withania somnifera, have distinct effects on viral RBD and host ACE2 receptor complex. Methods We employed molecular docking to screen thousands of phytochemicals against the ACE2-RBD complex, performed molecular dynamics (MD) simulation, and estimated the electrostatic component of binding free energy, along with the computation of salt bridge electrostatics. Results We report that W. somnifera compound, Withanone, docked very well in the binding interface of AEC2-RBD complex, and was found to move slightly towards the interface centre on simulation. Withanone significantly decreased electrostatic component of binding free energies of ACE2-RBD complex. Two salt bridges were also identified at the interface; incorporation of Withanone destabilized these salt bridges and decreased their occupancies. We postulate, such an interruption of electrostatic interactions between the RBD and ACE2 would block or weaken COVID-19 entry and its subsequent infectivity. Conclusion Our data, for the first time, show that natural phytochemicals could well be the viable options for controlling COVID-19 entry into host cells, and W. somnifera may be the first choice of herbs in these directions to curb the COVID-19 infectivity.

Accurate Electromechanical Characterization of Soft Molecular Monolayers using Piezo Force Microscopy

We report a new methodology for the electromechanical characterization of organic monolayers based on the implementation of dual AC resonance tracking piezo force microscopy (DART-PFM) combined with a sweep of an applied DC field under a fixed AC field. This experimental design allows calibration of the electrostatic component of the tip response and enables the use of low spring constant levers in the measurement. Moreover, the technique is shown to determine both positive and negative piezo response. The successful decoupling of the electrostatic component from the mechanical response will enable more quantitative electromechanical characterization of molecular and biomaterials and should generate new design principles for soft bio-compatible piezoactive materials. To highlight the applicability, our new methodology was used to successfully characterize the piezoelectric coefficient (d₃₃) of a variety of piezoactive materials, including self-assembled monolayers made of small molecules (dodecane thiol, mercaptoundecanoic acid) or macromolecules (peptides, peptoids), as well as a variety of inorganic materials, including lead zirconate titanate [PZT], quartz, and periodically poled lithium niobate [PPLN]. Due to high differential capacitance, the soft organic monolayers demonstrated exceedingly large electromechanical response (as high as 250 pm/V) but smaller d₃₃piezocoefficients. Finally, we find that the capacitive electrostatic response of the organic monolayers studied are significantly larger than conventional inorganic piezoelectric materials (e.g., PZT, PPLN, quartz), suggesting organic electromechanical materials applications can successfully draw from both piezo and electrostatic responses.

Accurate Electromechanical Characterization of Soft Molecular Monolayers using Piezo Force Microscopy

We report a new methodology for the electromechanical characterization of organic monolayers based on the implementation of dual AC resonance tracking piezo force microscopy (DART-PFM) combined with a sweep of an applied DC field under a fixed AC field. This experimental design allows calibration of the electrostatic component of the tip response and enables the use of low spring constant levers in the measurement. Moreover, the technique is shown to determine both positive and negative piezo response. The successful decoupling of the electrostatic component from the mechanical response will enable more quantitative electromechanical characterization of molecular and biomaterials and should generate new design principles for soft bio-compatible piezoactive materials. To highlight the applicability, our new methodology was used to successfully characterize the piezoelectric coefficient (d₃₃) of a variety of piezoactive materials, including self-assembled monolayers made of small molecules (dodecane thiol, mercaptoundecanoic acid) or macromolecules (peptides, peptoids), as well as a variety of inorganic materials, including lead zirconate titanate [PZT], quartz, and periodically poled lithium niobate [PPLN]. Due to high differential capacitance, the soft organic monolayers demonstrated exceedingly large electromechanical response (as high as 250 pm/V) but smaller d₃₃piezocoefficients. Finally, we find that the capacitive electrostatic response of the organic monolayers studied are significantly larger than conventional inorganic piezoelectric materials (e.g., PZT, PPLN, quartz), suggesting organic electromechanical materials applications can successfully draw from both piezo and electrostatic responses.

Accurate Electromechanical Characterization of Soft Molecular Monolayers using Piezo Force Microscopy

We report a new methodology for the electromechanical characterization of organic monolayers based on the implementation of dual AC resonance tracking piezo force microscopy (DART-PFM) combined with a sweep of an applied DC field under a fixed AC field. This experimental design allows calibration of the electrostatic component of the tip response and enables the use of low spring constant levers in the measurement. Moreover, the technique is shown to determine both positive and negative piezo response. The successful decoupling of the electrostatic component from the mechanical response will enable more quantitative electromechanical characterization of molecular and biomaterials and should generate new design principles for soft bio-compatible piezoactive materials. To highlight the applicability, our new methodology was used to successfully characterize the piezoelectric coefficient (d₃₃) of a variety of piezoactive materials, including self-assembled monolayers made of small molecules (dodecane thiol, mercaptoundecanoic acid) or macromolecules (peptides, peptoids), as well as a variety of inorganic materials, including lead zirconate titanate [PZT], quartz, and periodically poled lithium niobate [PPLN]. Due to high differential capacitance, the soft organic monolayers demonstrated exceedingly large electromechanical response (as high as 250 pm/V) but smaller d₃₃piezocoefficients. Finally, we find that the capacitive electrostatic response of the organic monolayers studied are significantly larger than conventional inorganic piezoelectric materials (e.g., PZT, PPLN, quartz), suggesting organic electromechanical materials applications can successfully draw from both piezo and electrostatic responses.