Sulfone Bridges Research Articles

Planarizable Push‐Pull Probes with Sulfoximine‐Bridged Dithienothiophene Acceptors

AbstractContrary to sulfides, sulfoxides or sulfones, sulfoximines have been mostly neglected in the design of fluorescent probes until recently. In this study, we elaborate systematically on sulfoximine acceptors in fluorescent flipper probes. Fluorescent flippers have been introduced as mechanosensitive probes to image membrane order and tension. They consist of twisted dithienothiophene dimers with sulfide and sulfone bridges to produce the essential primary dipole of the coupled push‐pull system. The objective of this study was to replace the sulfone acceptor by a series of sulfoximines. This is intriguing as a synthetic challenge and worthwhile because the extra nitrogen substituent offers a variability that is attractive to understand and control the performance of the probes. The new sulfoximine flippers provide corroborative evidence for the importance of the primary dipole of the planarizable push‐pull probe. Partitioning into differently ordered membranes and positioning within these different membranes is shown to correlate directly and dramatically with fluorescence lifetimes and mechanosensitivity. Sufficient partitioning into ordered membranes is confirmed as particularly important to image membrane tension by probe compression in the ground state. Compared to the conventional sulfone homolog, the best sulfoximine flipper has more red‐shifted absorption and emission maxima, longer fluorescence lifetime in cell membranes, and larger difference in lifetime upon application of membrane tension.

Effect of the Sulfonation on the Swollen State Morphology of Styrenic Cross-Linked Polymers.

The chemical structure and morphology of a set of sulfonic gel-type poly(styrene-divinylbenzene) resins (2 mol% DVB) prepared with different synthetic approaches were investigated by solid state NMR, Inverse Size Exclusion Chromatography (ISEC), FT-IR and elemental analysis to compare their swollen state structure. FT-IR and solid state NMR clearly show that the sulfonation mainly occurs in the para- position with respect the main polymer chain. Sensible proportions of sulfone bridges were found in the materials obtained with oleum and chlorosulfonic acid. With oleum, the presence of the sulfone bridges is clearly associated to a reduced ability to swell in the water medium relative to the proton exchange capacity. This highlights the cross-linking action of the sulfone bridges according to ISEC results, showing a high proportion of a dense polymer fraction in the swollen material. An even higher degree of sulfone-bridging, lower swelling ability, and a high proportion of a dense polymer fraction in the swollen material are found in the resin obtained with chlorosulfonic acid. As a matter of fact, Cross Polarization Magic Angle Spinning Nuclear Magnetic Resonance (CP-MAS 13C-NMR), elemental analysis, and ion exchange capacity, show that oleum and chlorosulfonic acid produced resins with remarkably smaller pores and lower swollen gel volume in polar solvents, with respect to concentrated sulfuric acid.

Sulfide, sulfoxide and sulfone bridged acyclic nucleoside phosphonates as inhibitors of the Plasmodium falciparum and human 6-oxopurine phosphoribosyltransferases: Synthesis and evaluation

Hypoxanthine-guanine-xanthine phosphoribosyltransferase (HGXPRT) is a recognized target for antimalarial chemotherapeutics. It synthesises all of the 6-oxopurine nucleoside monophosphates, IMP, GMP and XMP needed by the malarial parasite, Plasmodium falciparum (Pf). PfHGXPRT is also indirectly responsible for the synthesis of the adenosine monophosphate, AMP. The acyclic nucleoside phosphonates (ANPs) are a class of PfHGXPRT inhibitors. Prodrugs of these compounds are able to arrest the growth of Pf in cell culture. In the search for new inhibitors of PfHGXPRT, a series of sulfur containing ANPs (thia-ANPs) has been designed and synthesized. These compounds are based on the structure of 2-(phosphonoethoxy)ethylguanine (PEEG) and PEEHx which consist of a purine base (i.e. guanine or hypoxanthine) linked to a phosphonate group by five atoms i.e. four carbons and one oxygen. Here, PEEG and PEEHx were modified by substituting a sulfide, sulfoxide or a sulfone bridge for the oxygen atom in the linker. The effect of these substitutions on the Ki values for human HGPRT and PfHGXPRT was investigated and showed that most of the thia-ANPs distinctively favour PfHGXPRT. For example, the thia-analogue of PEEHx has a Ki value of 0.2 μM for PfHGXPRT, a value 25-fold lower than for the human counterpart. Prodrugs of these compounds have IC50 values in the 4–6 μM range in antimalarial cell-based assays, making them attractive compounds for further development as antimalarial drug leads.

Structure regulation of ZnS@g-C3N4/TiO2 nanospheres for efficient photocatalytic H2 production under visible-light irradiation

High-quality mesoporous or hollow ZnS@g-C3N4/TiO2 nanospheres were fabricated successfully via structure regulation strategy for efficient photocatalytic H2 production under visible-light irradiation. The entire process was started with the construction of solid ZnS@g-C3N4/TiO2 (S-ZnS@g-C3N4/TiO2) nanospheres. Then, via TiO2 nanosheets (NSs) in situ growth or Ostwald ripening treatment, S-ZnS@g-C3N4/TiO2 could be converted into mesoporous or hollow ZnS@g-C3N4/TiO2 nanospheres automatically. The obtained porous ZnS@g-C3N4/TiO2 nanospheres were featured of regular shape, high porosity, large specific surface area and adjustable g-C3N4 content. In mesoporous ZnS@g-C3N4/TiO2 (M-ZnS-g-C3N4/TiO2) nanospheres, the specially constructed mesoporous served as channels for the access of reactants in heterogeneous catalysis. Besides, the electron-sink function of ZnS NPs and C–SOx–C sulfone bridges between ZnS and g-C3N4 could improve visible-light H2 production of M-ZnS-g-C3N4/TiO2 significantly. Additionally, the prepared hollow ZnS@g-C3N4/TiO2 (H-ZnS@g-C3N4/TiO2) nanospheres showed a lower photocatalytic H2 production than M-ZnS-g-C3N4/TiO2 due to the decreased specific surface area. Compared with traditional g-C3N4 wrapping method, the proposed structure regulation strategy is simple, effective and structural controllable. Finally, a possible photocatalytic mechanism for visible-light H2 production by porous ZnS@g-C3N4/TiO2 nanospheres was tentatively proposed.

ChemInform Abstract: Recent Progress in the Synthesis and Application of Saddle‐Shaped Cyclooctatetrathiophenes and Their Derivatives

AbstractReview: 25 refs.

Recent Progress in the Synthesis and Application of Saddle‐shaped Cyclooctatetrathiophenes and Their Derivatives

AbstractCyclooctatetrathiophene (COTh) shows a novel saddle‐shaped molecular structure, which has been applied in organic synthesis and material science. In this paper, the design and synthesis of COThs and their derivatives were described. The derivatives of COThs include mainly four types. One is isomer with different sequences of the four thiophene rings; the second is oligomer such as dimmer and dendrimer; the third is derivative functionalized by substituent groups at the four α positions; the last is the one planarized by sulfur, silicon or sulfone bridges. The applications of COThs and their derivatives in molecular muscles and field effect transistors were also discussed.

Stabilized Sulfonated Aromatic Polymers by in situ Solvothermal Cross-Linking

The cross-link reaction via sulfone bridges of sulfonated polyetheretherketone (SPEEK) by thermal treatment at 180 °C in presence of dimethylsulfoxide (DMSO) is discussed. The modifications of properties subsequent to the cross-linking are presented. The mechanical strength as well as the hydrolytic stability increased with the thermal treatment time, i.e., with the degree of cross-linking. The proton conductivity was determined as function of temperature, IEC, degree of cross-linking and hydration number. The memory effect, which is the membrane ability to “remember” the water uptake reached at high temperature also at lower temperature, is exploited in order to achieve high values of conductivity. Membranes swelled at 110 °C can reach a conductivity of 0.14 S/cm at 80°C with a hydration number () of 73.

Highly Proton Conducting Electrolyte Membranes Based on Poly(arylene sulfone)s with Tetrasulfonated Segments

A series of fully aromatic polymers having only sulfone bridges linking the aromatic rings have been synthesized via polycondensations and studied as proton-exchange membranes. Mixtures of tetrasulfonated 4,4′-bis[(4-chlorophenyl)sulfonyl]-1,1′-biphenyl (BCPSBP), non-sulfonated BCPSBP, and 4,4′-thiobisbenzenethiol were copolymerized by nucleophilic aromatic substitution reactions to obtain sulfonated poly(arylene thioether sulfone)s (SPATSs) with ion exchange capacities (IECs) between 2.0 and 4.0 mequiv g–1. The thioether bridges of the SPATSs were quantitatively oxidized to sulfone bridges to obtain the corresponding sulfonated poly(arylene sulfone)s (SPASs). Small-angle X-ray scattering of dry SPATS and SPAS membranes showed that the tetrasulfonated segments promoted a distinct phase separation of the ionic groups already at quite low ionic contents. The SPAS polymers degraded between 300 and 340 °C in air, which was significantly above the degradation temperature of the corresponding SPATSs polymers. Moreover, SPAS membranes showed a significantly lower water uptake than the corresponding SPATS membranes. SPATS and SPAS membranes with IEC values of 2.4 and 2.2 mequiv g–1, respectively, maintained high proton conductivity at low relative humidity (RH). At 30% RH and 80 °C, these membranes reached 8 and 10 mS cm–1, respectively. The latter value coincided with that recorded for the state-of-the-art perfluorinated NRE212 membrane under the same conditions. Thus, the SPAS materials combine a straightforward synthetic pathway with a very robust polymer structure giving high proton conductivity at reduced RH.

Multiblock Copolymers Containing Highly Sulfonated Poly(arylene sulfone) Blocks for Proton Conducting Electrolyte Membranes

We report on multiblock copolymers consisting of highly sulfonated hydrophilic poly(arylene sulfone) (SPAS) blocks combined with hydrophobic poly(arylene ether sulfone) (PAES) blocks. Thiol-terminated precursor blocks of sulfonated poly(arylene thioether sulfone) (SPATS) were first prepared via polycondensations involving a novel tetrasulfonated dichlorotetraphenyldisulfone monomer, followed by coupling with pentafluorophenyl end-capped PAES precursor blocks under mild conditions to form SPATS–PAES block copolymers. The thioether bridges of the SPATS blocks were then selectively oxidized to obtain the SPAS–PAES copolymers with hydrophilic blocks containing exclusively sulfone bridges. Thus, the SPAS blocks were designed for high chain stiffness and stability toward desulfonation and had an ion exchange capacity (IEC) of 4.2 mequiv g–1. Membranes of the SPAS–PAES copolymers were phase separated on the nanoscale and showed an increased thermal stability and decreased water uptake in relation to the corresponding SPATS–PAES membranes. Meta-connectivity in the sulfonated blocks gave slightly higher water uptake than pure para-connectivity. At 80 °C and 30% relative humidity, the proton conductivity of a SPAS–PAES membrane with an IEC of 1.8 mequiv g–1 reached 5.1 mS cm–1, which was comparable to that of Nafion and far exceeded that of a sulfonated statistical copolymer membrane with a similar IEC. This class of block copolymers possesses very attractive properties and has great prospective to meet the demands of various electrochemical applications.

Effect of Crosslinking Time on Ion Exchange Capacity of Polystyrene Nanofiber Ion Exchangers

In this study, polystyrene nanofiber ion exchangers (PSNIE) were successfully prepared by a new method comprising of electrospinning and the subsequent crosslinking with formaldehyde and sulfonation in sulfuric acid to create the cation exchange functionality on the fibers surfaces. The PS solution at 15% w/v in dimethylacetamide (DMAc) produced the smallest PS nanofibers (399±38 nm) with good performance. The degree of crosslink and ion exchange capacity (IEC) of PSNIE depended upon the crosslinking time. The longer crosslinking time caused the greater crosslinked PS fibers. At the longest crosslinking time of 75 min, the remaining crosslinked PS fibers in dichloromethane were 94.12%; whereas, the starting fibers completely dissolved. This crosslinking agent (e.g. formaldehyde) might introduce methylene bridges in addition to sulfone bridges into the fibers. However, IEC decreased as crosslinking time increased, probably due to the difficulty of sulfonic functional groups to react with crosslinked PS fibers. The PSNIE crosslinked for 10 min showed the maximum IEC of 2.86 meq/g-dry-PSNIE, and the diameter of the PSNIE after sulfonation increased to 450-460 nm. Since cationic drug could be loaded onto this novel PSNIE, this nanofiber ion exchanger may be applied for controlled release delivery.

Properties and degradation of hydrocarbon fuel cell membranes: a comparative study of sulfonated poly(arylene ether sulfone)s with different positions of the acid groups

Sulfonated fully aromatic polymers with different positions of the acid groups, but with an identical polymer backbone, have been investigated and compared with respect to their properties as proton-exchange membranes. Three different series of sulfonated poly(arylene ether sulfone)s (SPAES) having the same backbone structure were prepared from 4,4′-dichlorodiphenyl sulfone (DCDPS) and 4,4′-dihydroxybiphenyl (BP), each series comprising three levels of the ion exchange capacity (IEC). The first series of SPAES had the sulfonic acid groups placed in ortho positions to the ether bridges (oeSPAES) and were prepared through post-polymerization sulfonation. The second and third series of SPAES carried the sulfonic acid groups in meta (msSPAES) and ortho (osSPAES) positions to the sulfone bridges, respectively, and were prepared by polycondensations of mixtures of BP, DCDPS and either 3,3′-disulfonated or 2,2′-disulfonated DCDPS, respectively. The latter monomer was synthesized via lithiation–sulfination–oxidation of DCDPS. Analysis of solvent cast membranes showed that the osSPAES copolymers had a high dimensional stability in water up to 100 °C, even at high ionic contents. Moreover, the osSPAES and the msSPAES membranes were better at retaining conductivity at reduced relative humidity than the oeSPAES membranes. Thermogravimetry of the membranes in the acid form under air indicated no significant differences based on the placement of the sulfonic acid groups. The resistance towards radical attack was analyzed by 1H NMR spectroscopy after immersing the membranes in Fenton's reagent at 60 °C, and the ability to retain IEC was found to increase in the order oeSPAES < msSPAES < osSPAES. Membrane stability was also studied in an accelerated hydrolysis test by immersing the membranes in 0.1 M aq. HCl at 200 °C in a sealed vessel. The results showed a dramatic loss of sulfonic acid in the oeSPAES membranes, presumably activated by the proximity of the ether bridges. Careful 1H NMR analysis also suggested that the osSPAES polymers degraded by scission of the sulfone bridges. The position of the sulfonic acid groups ortho to the sulfone bridges seemingly destabilized the latter under the severe conditions employed in the test.

Multiblock Copolymers with Highly Sulfonated Blocks Containing Di‐ and Tetrasulfonated Arylene Sulfone Segments for Proton Exchange Membrane Fuel Cell Applications

AbstractMultiblock copoly(arylene ether sulfone)s with different block lengths and ionic contents are tailored for durable and proton‐conducting electrolyte membranes. Two series of fully aromatic copolymers are prepared by coupling reactions between non‐sulfonated hydrophobic precursor blocks and highly sulfonated hydrophilic precursor blocks containing either fully disulfonated diarylsulfone or fully tetrasulfonated tetraaryldisulfone segments. The sulfonic acid groups are exclusively introduced in ortho positions to the sulfone bridges to impede desulfonation reactions and give the blocks ion exchange capacities (IECs) of 4.1 and 4.6 meq. g−1, respectively. Solvent cast block copolymer membranes show well‐connected hydrophilic nanophase domains for proton transport and high decomposition temperatures above 310 °C under air. Despite higher IEC values, membranes containing tetrasulfonated tetraaryldisulfone segments display a markedly lower water uptake than the corresponding ones with disulfonated diarylsulfone segments when immersed in water at 100 °C, presumably because of the much higher chain stiffness and glass transition temperature of the former segments. The former membranes have proton conductivities in level of a perfluorosulfonic acid membrane (NRE212) under fully humidified conditions. A membrane with an IEC of 1.83 meq. g−1 reaches above 6 mS cm−1 under 30% relative humidity at 80 °C, to be compared with 10 mS cm−1 for NRE212 under the same conditions.

Sulfonated poly(arylene ether sulfone) ionomers containing di- and tetrasulfonated arylene sulfone segments

Poly(arylene ether sulfone) (PSU) ionomers containing disulfonated aryl-SO2-aryl and tetrasulfonated aryl-SO2-aryl-aryl-SO2-aryl segments, respectively, were synthesized and studied to establish their structure–property relationships as proton-exchange membranes. High molecular weight PSUs with different distributions of sulfone bridges in the backbone were prepared by nucleophilic aromatic substitution reactions involving 4,4′-dichlorodiphenyl sulfone (DCDPS), 4,4′-bis[(4-chlorophenyl)sulfonyl]-1,1′-biphenyl (BCPSB), 4,4′-isopropylidenediphenol (bisphenol A), and 4,4′-(1,4-phenylenediisopropylidene)bisphenol (bisphenol P). The polymers were sulfonated viametallation and reaction with sulfur dioxide, followed by oxidation of the resulting sulfinates. This procedure allowed the introduction of two sulfonic acid units on electron-deficient aryl rings in ortho positions to each sulfone bridge of the PSUs. Analysis by small angle X-ray scattering of solvent cast membranes showed that ionic clustering was promoted in ionomers containing sulfonated BCPSB residues and flexible bisphenol P residues. The fully sulfonated PSUs had ion-exchange capacities (IECs) of 3.3–4.1 meq g−1 and were water soluble. However, partly sulfonated polymers with IECs of approx. 1.7 meq g−1 showed high proton conductivity at moderate water uptake and decomposed only above 240 °C during heating 1 °C min−1 under air. This work demonstrated that BCPSB residues can be conveniently and fully tetrasulfonated, which opens possibilities to prepare various aromatic copolymers and membranes with locally very high densities of hydrolytically stable sulfonic acid groups.

Fully Aromatic Block Copolymers for Fuel Cell Membranes with Densely Sulfonated Nanophase Domains

Two multiblock copoly(arylene ether sulfone)s with similar block lengths and ion exchange capacities (IECs) were prepared by a coupling reaction between a non-sulfonated precursor block and a highly sulfonated precursor block containing either fully disulfonated diarylsulfone or fully tetrasulfonated tetraaryldisulfone segments. The latter two precursor blocks were sulfonated via lithiation-sulfination reactions whereby the sulfonic acid groups were exclusively placed in ortho positions to the many sulfone bridges, giving these blocks IECs of 4.1 and 4.6 meq·g⁻¹, respectively. Copolymer membranes with IECs of 1.4 meq·g⁻¹ displayed well-connected hydrophilic nanophase domains and had decomposition temperatures at, or above, 300 °C under air. The copolymer with the tetrasulfonated tetraaryldisulfone segments showed a proton conductivity of 0.13 S·cm⁻¹ at 80 °C under fully humidified conditions, and surpassed that of a perfluorosulfonic acid membrane (NRE212) by a factor of 5 at -20 °C over time.

Cyclic Tetrathiophenes Planarized by Silicon and Sulfur Bridges Bearing Antiaromatic Cyclooctatetraene Core: Syntheses, Structures, and Properties

Cyclic tetrathiophenes 1, 2, and 3 planarized by dimethylsilyl, sulfur, and sulfone bridges bearing an antiaromatic cycloocatatetraene (COT) core were designed and synthesized to investigate the relationship among the bent angle, paratropicity, and HOMO-LUMO gap of the COT ring. The bent angles of the central COT rings of 1-3 were theoretically estimated and experimentally determined, and it was found that the planarity of the COT ring was finely adjusted in the order of 2 > 3 > 1 by using the small differences in the bond lengths between the bridging units and thiophene rings. From the comparisons of NICS values and calculated HOMO-LUMO gaps of cyclooctatetraene at various bent angles as well as the optimized structures of cyclic tetrathiophenes 1-3, similar enhancement of the paratropicity and narrowing of the HOMO-LUMO gap with decreasing bent angle of the COT rings were shown in both cyclooctatetraene and cyclic tetrathiophenes 1-3. Such predictions were experimentally proved for the first time by means of (1)H NMR and UV-vis measurements of 1-3. In comparison of the (1)H NMR chemical shifts of 1-3 with those of the corresponding precursors, upfield shifts due to a paratropic ring current in the COT ring were observed and the degree of shift increased with increasing planarity of the COT ring. Furthermore the colors of the solutions of 1 (lambda(max) = 483 nm), 2b (lambda(max) = 618 nm), and 3b (lambda(max) = 575 nm) were orange, purple, and red in CH(2)Cl(2), respectively, indicating that the HOMO-LUMO gaps of 1-3 become increasingly narrow with increasing planarity of the COT ring. Reflecting these electronic properties, CV measurements demonstrated the amphoteric redox properties of 1 and 2b, and the radical cation 1(*+), radical anion 1(*-), and dianion 1(2-) were chemically generated and successfully characterized by means of UV-vis, ESR, and NMR spectroscopies.

Synthesis and characterization of a water-soluble porphyrin with a cyclic sulfone

Water-soluble sulfonated tetraarylporphyrins are studied in a wide variety of contexts including as analytical reagents and as possible agents in cancer photodynamic therapy as well as in antiviral and antidiabetic applications. Herein, we report the first synthesis of a pentasulfonated porphyrin bearing an internal cyclic sulfone ring. Treatment of 5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrin (TPPS4) with fuming H 2SO 4 gave a structure consistent with initial sulfonation followed by dehydration to give a sulfone bridge between an ortho-position of one of the phenyl groups and a β-pyrrole position on the porphine ring (TPPS4Sc). The structure was established by electrospray mass spectrometry and 1H NMR. The Soret UV–visible absorption is red shifted by about 32 nm compared to that of TPPS4.

Thermal decomposition products of copoly(arylene ether sulfone)s characterized by direct pyrolysis mass spectrometry

Pyrolysis products with mass of up to 850 Da were detected by direct pyrolysis mass spectrometric (DPMS) analysis of a series of copoly(arylene ether sulfone)s (PES–PPO) synthesized by nucleophilic condensation of either 4,4′-dichlorodiphenylsulfone (CDPS) or 4,4′-bis-(4-chlorophenyl sulfonyl) biphenyl (long chain dichloride, LCDC) with different molar ratios of hydroquinone (HQ) or dihydroxydiphenylsulfone (HDPS). Pyrolysis products retaining the repeating units of the initial copolymers were formed at temperatures ranging from 420 °C to 470 °C (near the initial decomposition temperature). At temperatures higher than 450 °C were observed products containing biphenyl units, formed by the elimination process of SO 2 from diphenyl sulfone bridges. Products having biphenyl and dibenzofuran moieties were detected in the mass spectra recorded at temperatures above 550 °C. These units were formed by loss of hydrogen atom from diphenyl ether bridges. Although the EI (18 eV) mass spectra of the pyrolysis products of the samples investigated were very similar, it was found that the relative intensity of some ions reflects the molar composition of the copolymers analysed. Cyclic and linear oligomers with very low molecular mass, present in the crude copolymers, were also detected by DPMS. Thermogravimetric analysis also showed their excellent thermal stability below 400 °C. It indicates that the copolymers yield a char residue of 40–45% at 800 °C, which increases with the PPO mole fraction in the samples.

Crosslinked Organic/Inorganic Hybrid Proton Exchange Polymeric Membranes

ABSTRACTA general, efficient and experimentally simple method for the synthesis of covalently crosslinked class II hybrid polymers based on PolyEtherEtherKetone (PEEK) with a high degree of sulfonation (DS = 0.8) was performed. The synthetic strategy foreseen two steps: the first one, direct sulfonation, led to the introduction of sulfonic acid groups and to the formation of sulfone bridges among repeat units. The second step, lithiation and silylation, led to the formation of covalent bonds between the organic backbone and Si(OH)3 moieties. The materials were characterized by 1H NMR Spectroscopy, ATR/FTIR Spectroscopy, Thermogravimetric Analysis (TGA) and Mass Spectrometry. Preliminary proton conduction measurements in dry conditions were performed. The introduction of silicon groups in the system improved thermal stability.

Synthesis and Properties of Oligodeoxynucleotide Analogues with Bis(methylene) Sulfone Bridges.

Synthesis and Properties of Oligodeoxynucleotide Analogues with Bis(methylene) Sulfone Bridges.

Synthesis and Properties of Oligodeoxynucleotide Analogs with Bis(methylene) Sulfone Bridges

AbstractA convergent, solution‐phase synthesis was developed for the bis(methylene) sulfone‐bridged oligodeoxynucleotide analogs (SNA) 5′‐d(HOCH2‐Tso2Tso2Tso2Cso2Tso2Tso2Tso2T‐CH2SO$\rm{_{3}^{-}}$)‐3′ (35b) and 5′‐d(HOCH2‐Tso2Tso2Tso2Tso2Tso2Tso2Tso2T‐CH2SO$\rm{_{3}^{-}}$)‐3′ (34c) (SO2 corresponds to CH2SO2CH2 instead of OP(O)(O−)(O). In these, the phosphodiester linkages are replaced by non‐ionic bis(methylene) sulfone linkers. The general strategy involved convergent coupling of 3′,5′‐bishomo‐β‐D‐deoxyribonucleotide analogs functionalized at the 6′‐end (CH2C(5′)) as bromides or mesylates and at the CH2C(3′) position as thiols, with the resulting thioether being oxidized to the corresponding sulfone. A single charge was introduced at the terminal CH2C(3′) position of the octamers to increase their solubility in water. During the synthesis, it became apparent that the key intermediates generated secondary structures through either folding or aggregation in a variety of solvents. This generated unusual reactivity and was unique for very similar structures. For example, although the dimeric thiol d(BzOCH2‐Tso2C‐CH2SH) (14b) was a well‐behaved synthetic intermediate, the tetrameric thiol d(TrOCH2‐Tso2Tso2Tso2toC‐CH2SH) derived from the corresponding thioacetate was rapidly converted to a disulfide by very small amounts of oxidant (28→29, Scheme 6), while the analogous tetrameric thiol d(BzOCH2‐Tso2TsTso2T‐CH2SH) (26), differing only by a single heterocycle, was oxidized much more slowly (Bz=PhCO, Tr=Ph3C, to=2‐MeC6H4CO (at N4 of dc)). The sequence‐dependent reactivity, well known in many classes of natural products (including polypeptides), is not prominent in natural oligonucleotides. These results are discussed in light of the proposal that the repeating negative charge in nucleic acids is key to their ability to serve as genetic molecules, in particular, their capability to support Darwinian evolution. The ability of 5′‐d(HOCH2‐Tso2Tso2Tso2Cso2Tso2Tso2Tso2T‐CH2SO$\rm{_{3}^{-}}$)‐3′ (35b) to bind as a third strand to duplex DNA was also examined. No triple‐helix‐forming propensity was detected in this molecule.