5H-EAF · two-channel · ChemRxiv v7biochemdefensetech.com

pH-gated two-channel histidine nanochelant for electrostatic interception of polycationic species and soft heavy metals

BioChem Defense Technology (BCDT) develops 5H-EAF—an erythritol-capped linear penta-histidine peptide (MW ≈ 868 Da; C₃₆H₄₉N₁₅O₁₁) whose five imidazoles (pKa ≈ 6.0–6.1) define Channel E at endosomal pH and Channel C at physiologic pH. Public materials describe non-confidential science from ChemRxiv v7, under dual-use stewardship.

Brand mark · BCDT

BCDT — BioChem Defense Technology
5H-EAF: reversible, pH-gated two-channel histidine nanochelant — electrostatic interception of polycationic species and soft heavy metals. Inquiry-first identity.
Platform
5H-EAF two-channel nanochelant
Public science
ChemRxiv v7 (CC-BY)
Governance
Dual-use stewardship

Positioning

One molecule. Two channels. One titration curve.

Channel E (His⁺, endosomal pH 5.5–6.5, net +4 to +5): competitive occupancy of acidic sites and local neutralization of negative endosomal-pore potential. The effect is electrostatic screening, not mechanical occlusion.

Channel C (His⁰, pH ~7.4): imidazole-N coordination that prefers Hg(II) and Pb(II); Zn(II) and Cu(I) remain weakly bound. The cycle is a reversible electrostatic switch, not a permanent steric block.

This public site presents only non-confidential science from the open v7 preprint: mechanism abstracts, computational validation summaries, and dual-use governance language. No controlled recipes, production protocols, or weaponization pathways.

Technology

5H-EAF — pH-gated two-channel histidine nanochelant

High-level, non-confidential description of the published platform. Structural and computational detail lives in the ChemRxiv preprint (v7). Full computational packages remain under appropriate agreements.

Composition (public abstract)

  • Scaffold: erythritol-capped linear penta-histidine peptide
  • MW: ≈ 868 Da (C₃₆H₄₉N₁₅O₁₁; as reported in v7)
  • pKa: ≈ 6.0–6.1 (five imidazole side chains)
  • Design principle: inverse of classic histidine-release systems—Channel E on when protonated at endosomal pH
  • Validation: DFT (B3LYP-D3/def2-TZVP), multi-replica MD / MM-PBSA, and a 34-node NetworkX model as published

01

Channel C · physiologic pH ~7.4

Charge collapses as the five imidazoles deprotonate. Channel C is the soft-metal coordination window—preferential imidazole-N ligation of Hg(II) and Pb(II), with Zn(II) and Cu(I) remaining weakly bound.

02

Channel E · endosomal pH 5.5–6.5

Histidine protonation drives a net +4 to +5 charge. Channel E supports competitive occupancy of acidic sites and local neutralization of negative endosomal-pore potential—electrostatic screening, not mechanical occlusion.

03

Reversible electrostatic switch

Return to neutrality reverses binding for release and reagent recycling. The functional cycle is a single, reversible electrostatic switch rather than a permanent steric block.

Two-channel switch (public summary)

At endosomal pH 5.5–6.5 the molecule protonates to a net charge of approximately +4 to +5 (Channel E dominant). At physiologic pH the charge collapses (Channel C dominant), enabling preferential coordination of soft heavy-metal ions. Return to neutrality reverses binding. This reversible electrostatic switch is the core of the published platform.

Channel E

pH 5.5 – 6.5

Channel C

pH ~7.4

pKa

≈ 6.0 – 6.1

Applications

Research directions framed for protection

Dual-use by nature: the same electrostatic / pH logic spans biodefense-relevant modeling and soft heavy-metal research. Everything below is research framing, not product claims. The public educational companion cited in v7 Methods is MoleculoSphere 5D.

Biodefense-relevant modeling

Computational evaluation of electrostatic engagement with furin-processed polycationic motifs and endosomal pore architectures — framed as protective research at the non-confidential abstract level.

Soft heavy-metal detoxification research

Channel C coordination of Hg(II) / Pb(II) class cations as reported in the v7 preprint. Zn(II) and Cu(I) remain weakly bound — this is not a copper or zinc chelator claim.

Neuroinflammation & copper-transport context

Research framing connecting metal homeostasis (including ATP7A/ATOX1-related pathways), endosomal chemistry, and inflammatory stress — without clinical claims or treatment protocols.

Systems & quantum-classical validation

DFT (ORCA; B3LYP-D3/def2-TZVP), multi-replica MD, and MM-PBSA, plus a 34-node directed network (NetworkX). In that computational model the GLP1R safety node is unperturbed at both pH values.

v7 Methods ref. 20 · educational companion · v1.1 · locked kernel

MoleculoSphere 5D

The public Debye–Hückel / Yukawa continuum kernel cited in the v7 Methods section. A browser-only educational / hypothesis-generation tool that visualizes mean interaction energies between a curated public ligand set and six public receptor region-of-interest proxies under a locked, reproducible kernel — not a structural model of 5H-EAF, and not a diagnostic or therapeutic claim.

Layered disclosure: the proprietary 5H-EAF ligand is intentionally excluded from this public educational set, even though composition is described in the open preprint. Dual-use stewardship applies — protective mission framing only; no controlled technical data.

Public receptors
A–F · furin triad · acidic pore · α7 · ATP7A
Public ligands
Pb²⁺ · Cu²⁺ (E/F) · KSRRRAR · PRARR · SLLRST

Science & data

Open preprint — the public evidence layer

This public site summarizes only the open ChemRxiv record (CC-BY) by Esteban A. Fridman, MD, PhD, BioChem Defense Technology. Preprints are not peer-reviewed; data may be preliminary. Binding free energies remain computational predictions — v7 reports no experimental dissociation constants. Full computational packages remain under appropriate agreements.

Open ChemRxiv v7
ChemRxiv preprint · CC-BY 4.0 · v7 · 27 Aug 2026

pH-Gated Two-Channel Histidine Nanochelant for Electrostatic Interception of Furin-Processed Polycationic Species and Soft Heavy Metals

Canonical public platform paper (v7) — two-channel pH-gated mechanism, soft-metal coordination, biodefense-relevant electrostatic modeling.

Fridman EA. pH-Gated Two-Channel Histidine Nanochelant for Electrostatic Interception of Furin-Processed Polycationic Species and Soft Heavy Metals. ChemRxiv. 2026. doi:10.26434/chemrxiv.15000714/v7 (preprint, CC-BY 4.0; not peer-reviewed).

doi:10.26434/chemrxiv.15000714/v7

https://chemrxiv.org/doi/full/10.26434/chemrxiv.15000714/v7
Open preprint

What the public record supports

Two-channel switchChannel E endosomal (pH 5.5–6.5) · Channel C physiologic (pH ~7.4)
ChargeNet +4 to +5 when protonated (Channel E)
pKa≈ 6.0–6.1 (five imidazole side chains)
MethodsDFT (B3LYP-D3/def2-TZVP) · multi-replica MD · MM-PBSA · NetworkX 34-node
Continuum layerMoleculoSphere 5D (Yukawa / Debye–Hückel), cited in v7 Methods
Channel C metalsHg(II), Pb(II) preferred · Zn(II), Cu(I) weakly bound
GLP1RUnperturbed in the computational 34-node network at both pH values
CycleReversible electrostatic switch, not a permanent steric block
ScopeComputational predictions; no experimental Kd in this preprint

Dual-use stewardship

Beneficial science under explicit dual-use discipline

A platform that can inform biodefense research and metal detoxification is dual-use by definition. We treat that as a first-class design constraint—not a footnote.

  • Protective mission only

    Public programs are oriented to health, environment, infrastructure resilience, and legitimate biodefense research—not offensive use.

  • Layered disclosure

    Capability abstracts and preprint-level science publicly; sensitive implementation detail only under need-to-know agreements.

  • Partner diligence

    Collaboration requests are screened for legitimate protective use and appropriate controls before deeper exchange.

Dual-use statement

We develop and discuss technology for identifying and reducing biological and chemical harm. We do not provide public guidance that would materially assist the creation, weaponization, or covert deployment of biological or chemical agents.

In scope (public)

v7 two-channel preprint abstract, pH-switch summary, dual-use governance language, high-level applications, and the public educational electrostatics tool (MoleculoSphere 5D).

Out of scope (public)

Agent production, weaponization steps, targeting doctrine, or export-controlled technical datasets.

Team

Founder

Esteban A. Fridman, MD, PhD

Founder · BioChem Defense Technology (BCDT) · Austin, TX

Physician-scientist leading computational and biophysical research on pH-gated histidine nanochelants. Corresponding author on the public v7 ChemRxiv preprint describing the two-channel 5H-EAF platform — electrostatic interception of polycationic species and soft heavy metals. Prior training and research experience includes neuro / TBI-relevant clinical science; public materials emphasize protective mission and dual-use discipline.

Contact

Request a non-confidential briefing

For research collaboration, preprint discussion, dual-use review, or capability briefings limited to non-confidential scope.

Ideal partners: labs, public agencies, biodefense programs, and industry teams with a protective mission.

Do not send: controlled technical data, classified content, or detailed agent-production information via this form.

Do not submit controlled technical data, classified material, or detailed agent-production information through this form.