Base Pairing of 8‐Aza‐7‐deazapurine‐2,6‐diamine Linked via the N(8)‐Position to the DNA Backbone: Universal Base‐Pairing Properties and Formation of Highly Stable Duplexes when Alternating with dT

The unusually N⁸‐glycosylated pyrazolo[3,4‐d]pyrimidine‐4,6‐diamine 2′‐deoxyribonucleoside ( 3 ) was synthesized and converted to the phosphoramidite 11 . Oligonucleotides were prepared by solid‐phase synthesis, and the base pairing of compound 3 was studied. In non‐self‐complementary duplexes containing compound 3 located opposite to the four canonical DNA constituents, strong base pairs are formed that show ambiguous pairing properties. The self‐complementary duplex d( 3 ‐T)₆ ( 34 ⋅ 34 ) is significantly more stable than d(A‐T)₆.     

Conformational analysis of trinucleotides containing a single abasic residue; mimics of DNA damage

The conformations of three deoxytrinucleotide analogues [d(TpXpT), where X = T, tetrahydrofuran (THF) or propyl (Pr)] were investigated using ¹H NMR spectroscopy as part of our studies of DNA‐base damage. The phosphorus‐decoupled ¹H NMR spectrum of each compound was simulated and values for the vicinal proton–proton coupling constants of the sugar ring hydrogens were extracted at several different temperatures, for use in conformational analyses. It was found that the south‐pucker preference of the sugar 3′ to the modification is increased whereas that of the 5′ is decreased relative to the puckers observed for the non‐modified system. The conformational change is <25%. This subtle effect may be sufficient for recognition by DNA repair enzymes. Copyright © 2003 John Wiley & Sons, Ltd.     

Glycosylated Cell‐Penetrating Poly(disulfide)s: Multifunctional Cellular Uptake at High Solubility

The glycosylation of cell‐penetrating poly(disulfide)s (CPDs) is introduced to increase the solubility of classical CPDs and to achieve multifunctional cellular uptake. With the recently developed sidechain engineering, CPDs decorated with α‐d ‐glucose (Glu), β‐d ‐galactose (Gal), d ‐trehalose (Tre), and triethyleneglycol (TEG) were readily accessible. Confocal laser scanning microscopy images of HeLa Kyoto cells incubated with the new CPDs at 2.5 μm revealed efficient uptake into cytosol and nucleoli of all glycosylated CPDs, whereas the original CPDs and TEGylated CPDs showed much precipitation into fluorescent aggregates at these high concentrations. Flow cytometry analysis identified Glu‐CPDs as most active, closely followed by Gal‐CPDs and Tre‐CPDs, and all clearly more active than non‐glycosylated CPDs. In the MTT assay, all glyco‐CPDs were non‐toxic at concentrations as high as 2.5 μm . Consistent with thiol‐mediated uptake, glycosylated CPDs remained dependent on thiols on the cell surface for dynamic covalent exchange, their removal with Ellman's reagent DTNB efficiently inhibited uptake. Multifunctionality was demonstrated by inhibition of Glu‐CPDs with d ‐glucose (IC₅₀ ca. 20 mm ). Insensitivity toward l ‐glucose and d ‐galactose and insensitivity of conventional CPDs toward d ‐glucose supported that glucose‐mediated uptake of the multifunctional Glu‐CPDs involves selective recognition by glucose receptors at the cell surface. Weaker but significant sensitivity of Gal‐CPDs toward d ‐galactose but not d ‐glucose was noted (IC₅₀ ca. 110 mm ). Biotinylation of Glu‐CPDs resulted in the efficient delivery of streptavidin together with a fluorescent model substrate. Protein delivery with Glu‐CPDs was more efficient than with conventional CPDs and remained sensitive to DTNB and d ‐glucose, i.e., multifunctional.     

Functionalized 2‐Hydrazinobenzothiazole with Isatin and Some Carbohydrates under Conventional and Ultrasound Methods and Their Biological Activities

Several chemical reactions were carried out on 3‐(benzothiazol‐2‐yl‐hydrazono)‐1,3‐dihydro‐indol‐2‐one ( 2 ). 3‐(Benzothiazol‐2‐yl‐hydrazono)‐1‐alkyl‐1,3‐dihydro‐indol‐2‐one 3a , 3b , 3c have been achieved. Reaction of compound 2 with ethyl bromoacetate in the presence of K₂CO₃ resulted the uncyclized product 4 . Reaction of compound 2 with benzoyl chloride afforded dibenzoyl derivative 5 . Compound 2 was smoothly acetylated by acetic anhydride in pyridine to give diacetyl derivative 6b . Moreover, when compound 4 reacted with methyl hydrazine, it yielded dihydrazide derivative 7 , whereas the hydrazinolysis of this compound with hydrazine hydrate gave the monohydrazide derivative 8 . {N‐(Benzothiazol‐2‐yl‐N′‐(3‐oxo‐3,4‐dihydro‐2H‐1,2,4‐triaza‐fluoren‐9‐ylidene)hydrazino]‐acetic acid ethyl ester ( 9 ) was prepared by ring closure of compound 8 by the action of glacial acetic acid. In addition, the reaction of 2‐hydrazinobenzothiazole ( 1 ) with d ‐glucose and d ‐arabinose in the presence of acetic acid yielded the hydrazones 10a , 10b , respectively. Acetylation of compound 10b gave compound 11b . On the other hand, compound 13 was obtained by the reaction of compound 1 with gama‐d ‐galactolactone ( 12 ). Acetylation of compound 13 with acetic anhydride in pyridin gave the corresponding N¹‐acetyl‐N²‐(benzothiazolyl)‐2‐yl)‐2,3,4,5,6‐penta‐O‐acetyl‐d ‐galacto‐hydrazide ( 14 ). Better yields and shorter reaction times were achieved using ultrasound irradiation. The structural investigation of the new compounds is based on chemical and spectroscopic evidence. Some selected derivatives were studied for their antimicrobial and antiviral activities.     

trans‐4‐[4‐(Dimethylamino)phenyl­iminomethyl]‐N‐phenylpyridinium hexafluorophosphate

The crystal structure of the dipolar chromophoric title compound, C₂₀H₂₀N₃⁺·PF₆^?, is described. The phenyl­ene and pyridyl rings are almost coplanar [dihedral angle 7.5 (2)°], but the phenyl substituent forms a dihedral angle of 56.6 (1)° with the pyridyl ring. The compound crystallizes in the non‐centrosymmetric space group Cc and is a likely candidate for the display of quadratic non‐linear optical effects.     

Attachment of Chloride Anion to Sugars: Mechanistic Investigation and Discovery of a New Dopant for Efficient Sugar Ionization/Detection in Mass Spectrometers

A new method for efficient ionization of sugars in the negative‐ion mode of electrospray mass spectrometry is presented. Instead of using strongly hydrophobic dopants such as dichloromethane or chloroform, efficient ionization of sugars has been achieved by using aqueous HCl solution for the first time. This methodology makes it possible to use hydrophilic dopants, which are more appropriate for chromatographic separation techniques with efficient sugar ionization and detection in mass spectrometry. The interaction between chloride anions and monosaccharides (glucose and galactose) was studied by DFT in the gas phase and by implementing the polarizable continuum model (PCM) for calculations in solution at the high B3LYP/6‐31+G(d,p)//B3LYP/6‐311+G(2d,p) level of theory. In all optimized geometries of identified [M+Cl]^? anions, a non‐covalent interaction exists. Differences were revealed between monodentate and bidentate complex anions, with the latter having noticeably higher binding energies. The calculated affinity of glucose and galactose toward the chloride anion in the gas phase and their chloride anion binding energies in solution are in excellent agreement with glucose and galactose [M+Cl]^? experimental intensity profiles that are represented as a function of the chloride ion concentration. Density functional calculations of gas‐phase affinities toward chloride anion were also performed for the studied disaccharides sucrose and gentiobiose. All calculations are in excellent agreement with the experimental data. An example is introduced wherein HCl was used to effectively ionize sugars and form chlorinated adduct anions to detect sugars and glycosylated metabolites (anthocyanins) in real biological systems (Vitis vinifera grape extracts and wines), whereas they would not have been easily detectable under standard infusion electrospray mass spectrometry conditions as deprotonated species.     

Increasing the Bioavailability of RuIII Anticancer Complexes through Hydrophobic Albumin Interactions

A series of pyridine‐based derivatives of the clinically successful Ru^III‐based complexes indazolium [trans‐RuCl₄(1 H‐indazole)₂] (KP1019) and sodium [trans‐RuCl₄(1 H‐indazole)₂] (KP1339) have been synthesized to probe the effect of hydrophobic interactions with human serum albumin (hsA) on anticancer activity. The solution behavior and protein interactions of the new compounds were characterized by using electron paramagnetic resonance (EPR) and UV/Vis spectroscopy. These studies have revealed that incorporation of hydrophobic substituents at the 4′‐position of the axial pyridine ligand stabilizes non‐coordinate interactions with hsA. As a consequence, direct coordination to the protein is inhibited, which is expected to increase the bioavailability of the complexes, thus potentially leading to improved anticancer activity. By using this approach, the lifetimes of hydrophobic protein interactions were extended from 2 h for the unsubstituted pyridine complex, to more than 24 h for several derivatives. Free complexes were tested for their anticancer activity against the SW480 human colon carcinoma cell line, exhibiting low cytotoxicity. Pre‐treatment with hsA improved the solubility of every compound and led to some changes in activity. Particularly notable was the difference in activity between the methyl‐ and dibenzyl‐functionalized complexes. The former shows reduced activity after incubation with hsA, indicating reduced bioavailability due to protein coordination. The latter exhibits little activity on its own but, following treatment with hsA, exhibited significant cytotoxicity, which is consistent with its ability to form non‐coordinate interactions with the protein. Overall, our studies demonstrate that non‐coordinate interactions with hsA are a viable target for enhancing the activity of Ru^III‐based complexes in vivo.     

MOF‐Derived Spinel NiCo2O4 Hollow Nanocages for the Construction of Non‐enzymatic Electrochemical Glucose Sensor

Non‐enzymatic glucose sensor is greatly expected to take over its enzymatic counterpart in the future. In this paper, we reported on a facile strategy to construct a non‐enzymatic glucose sensor by use of NiCo₂O₄ hollow nanocages (NiCo₂O₄ HNCs) as catalyst, which was derived from Co‐based zeolite imidazole frame (ZIF‐67). The NiCo₂O₄ HNCs modified glassy carbon electrode (NiCo₂O₄ HNCs/GCE), the key component of the glucose sensor, showed highly electrochemical catalytic activity towards the oxidation of glucose in alkaline media. As a result, the proposed non‐enzymatic glucose sensor afforded excellent analytical performances assessed with the aid of cyclic voltammetry and amperometry (i–t). A wide linear range spanning from 0.18 μΜ to 5.1 mM was achieved at the NiCo₂O₄ HNCs/GCE with a high sensitivity of 1306 μA mM^?1 cm^?2 and a fast response time of 1 s. The calculated limit of detection (LOD) of the sensor was as low as 27 nM (S/N=3). Furthermore, it was demonstrated that the non‐enzymatic glucose sensor showed considerable anti‐interference ability and excellent stability. The practical application of the sensor was also evaluated by determination of glucose levels in real serum samples.     

Highly Stable Double‐Stranded DNA Containing Sequential Silver(I)‐Mediated 7‐Deazaadenine/Thymine Watson–Crick Base Pairs

The oligonucleotide d(TX)₉, which consists of an octadecamer sequence with alternating non‐canonical 7‐deazaadenine (X) and canonical thymine (T) as the nucleobases, was synthesized and shown to hybridize into double‐stranded DNA through the formation of hydrogen‐bonded Watson–Crick base pairs. dsDNA with metal‐mediated base pairs was then obtained by selectively replacing W‐C hydrogen bonds by coordination bonds to central silver(I) ions. The oligonucleotide I adopts a duplex structure in the absence of Ag⁺ ions, and its stability is significantly enhanced in the presence of Ag⁺ ions while its double‐helix structure is retained. Temperature‐dependent UV spectroscopy, circular dichroism spectroscopy, and ESI mass spectrometry were used to confirm the selective formation of the silver(I)‐mediated base pairs. This strategy could become useful for preparing stable metallo‐DNA‐based nanostructures.     

A Multifunctional MnII Phosphonate for Rapid Separation of Methyl Orange and Electron‐Transfer Photochromism

A Mn^II phosphonate of the general formula [Mn(H₂L)₂(H₂O)₂(H₂bibp)] adopts a layered motif with protonated H₂bibp²⁺ cations embedded in the channels (H₄L=thiophene‐2‐phosphonic acid; bibp=4,4′‐bis(1‐imidazolyl)biphenyl). The title compound exhibits excellent adsorptive removal of methyl orange (MO) dye from aqueous solution. Its advantageous features include fast adsorption, high uptake capacity, selective removal, and reusability, which are of great significance for practical application in wastewater treatment. Meanwhile, the compound displays rapid photochromism upon irradiation with visible light at room temperature. Extensive research has demonstrated that such behavior is based on a ligand‐to‐ligand charge‐transfer (LLCT) mechanism. The irradiated sample possesses an ultra‐long‐lived charge‐separated state. Moreover, not only is the compound the first Mn‐based photochromic MOF, but it is also one of the very few examples showing LLCT with non‐photochromic components.     

A Novel Spiro[acridine‐9,9′‐fluorene] Derivatives Containing Phenanthroimidazole Moiety for Deep‐Blue OLED Application

Typical π–π stacking and aggregation‐caused quenching could be suppressed in the film‐state by the spiro conformation molecular design in the field of organic light‐emitting diodes (OLEDs). Herein, a novel deep‐blue fluorescent material with spiro conformation, 1‐(4‐(tert ‐butyl)phenyl)‐2‐(4‐(10‐phenyl‐10H ‐spiro[acridine‐9,9′‐fluoren]‐2‐yl)phenyl)‐1H ‐phenanthro[9,10‐d ]imidazole ( SAF‐BPI ), was designed and synthesized. The compound consists of spiro‐acridine‐fluorene (SAF) as donor part and phenanthroimidazole (BPI) as acceptor part. Owing to the rigid SAF skeleton, this compound exhibits a high thermal stability with a glass transition temperature (T _g) of 198 °C. The compound exhibits bipolar transporting characteristics demonstrated by the single‐carrier devices. The non‐doped OLEDs based on the SAF‐BPI as the emitting layer shows maximum emission at 448 nm, maximum luminance of 2122 cd m⁻², maximum current efficiency (CE) of 3.97 cd A⁻¹, and a maximum power efficiency of 2.08 lm W⁻¹. The chromaticity coordinate is stable at (0.15, 0.10) at the voltage of 7–11 V. The device shows a slow efficiency roll‐off with CE of 3.35 and 2.85 cd A⁻¹ at 100 and 1000 cd m⁻², respectively.     

An Improved Protocol for the Synthesis of 2‐Nitro‐7,8,17,18‐tetrabromo‐5,10,15,20‐tetraphenylporphyrin and its Conformational Aspects by Electrochemistry and Spectroscopy

An improved methodology is reported for the synthesis of 2‐nitro‐7,8,17,18‐tetrabromo‐5,10,15,20‐tetraphenylporphyrin by the β‐mononitration of 2,3,12,13‐tetrabromo‐5,10,15,20‐tetraphenylporphyrin using 50% HNO₃. The copper derivative of this compound showed the expected trend in redox potentials where the free‐base form showed an opposite one on comparing with the corresponding non‐nitro analogs. This opposite trend is ascribed to the role of nitro group in dictating the extent of nonplanarity of the porphyrin as indicated by the electronic and ¹H NMR spectral studies.     

Selective Electrochemical Detection of Pirarubicin by Means of DNA‐modified Graphite Biosensor

Pirarubicin (THP) is an anthracycline drug, which is mainly used in the anticancer treatment. Utilization of THP may be associated with many dangerous side effects, therefore monitoring of drug level in patients’ organism is an important aspect of chemotherapy. In our research we focused on designing of an electrochemical DNA‐based biosensor for selective detection of pirarubicin (THP). Our biosensor utilizes the ability of pirarubicin to interact with DNA double helix and the fact that THP is an electrochemically active compound. Graphite electrodes modified with DNA enable to obtain nearly three thousand times higher sensitivity (41.8⋅10³ A/M) than non‐modified sensors. Furthermore, in the case of THP detection by means of bare graphite electrodes, LOD was 43.6⋅10⁻⁹ M, whereas for developed DNA biosensors ‐112⋅10^‐12 M. A study of selectivity of DNA–modified biosensors was carried out in aqueous solutions containing interferents: acetaminophen (PCT) and ascorbic acid (AA) as well as in samples of fetal bovine serum (FBS) spiked with PCT and AA. In established measurement conditions one peak corresponding to THP reduction was observed, whereas no redox peaks assigned to interferents (PCT, AA) were present. These results indicate that developed biosensors are selective to pirarubicin.     

Impact of the Synergistic Collaboration of Oligothiophene Bridges and Ruthenium Complexes on the Optical Properties of Dumbbell‐Shaped Compounds

The linear and non‐linear optical properties of a family of dumbbell‐shaped dinuclear complexes, in which an oligothiophene chain with various numbers of rings (1, 3, and 6) acts as a bridge between two homoleptic tris(2,2′‐bipyridine)ruthenium(II) complexes, have been fully investigated by using a range of spectroscopic techniques (absorption and luminescence, transient absorption, Raman, and non‐linear absorption), together with density functional theory calculations. Our results shed light on the impact of the synergistic collaboration between the electronic structures of the two chemical moieties on the optical properties of these materials. Experiments on the linear optical properties of these compounds indicated that the length of the oligothiophene bridge was critical for luminescent behavior. Indeed, no emission was detected for compounds with long oligothiophene bridges (compounds 3 and 4 , with 3 and 6 thiophene rings, respectively), owing to the presence of the ³π? π* state of the conjugated bridge below the ³MLCT‐emitting states of the end‐capping Ru^II complexes. In contrast, the compound with the shortest bridge ( 2 , one thiophene ring) shows excellent photophysical features. Non‐linear optical experiments showed that the investigated compounds were strong non‐linear absorbers in wide energy ranges. Indeed, their non‐linear absorption was augmented upon increasing the length of the oligothiophene bridge. In particular, the compound with the longest oligothiophene bridge not only showed strong two‐photon absorption (TPA) but also noteworthy three‐photon‐absorption behavior, with a cross‐section value of 4×10^?78 cm⁶ s² at 1450 nm. This characteristic was complemented by the strong excited‐state absorption (ESA) that was observed for compounds 3 and 4 . As a matter of fact, the overlap between the non‐linear absorption and ESA establishes compounds 3 and 4 as good candidates for optical‐power‐limiting applications.     

Intercalating Nucleic Acids with Insertion of 5‐[(Pyren‐1‐yl)methylidene]hydantoin‐Substituted Butane‐1,2‐diol

Isopropylidene‐protected (S)‐4‐O‐(methylsulfonyl)butane‐1,2,4‐triol was used for alkylation of 5‐[(pyren‐3‐yl)methylidene]hydantoin to give the N³‐monoalkylated product 4 in 29% yield together with a dialkylated product 5 in 12% yield. After deprotection, compound 4 was transformed into a dimethoxytrityl (DMT)‐protected phosphoramidite building block 9 for standard DNA synthesis. When inserted as a bulge in the triplex‐forming oligomer, compound 6 stabilizes a DNA triplex, whereas the corresponding DNA/DNA and DNA/RNA duplexes are slightly destabilized. For the triplex, fluorescence enhancement was observed at 500 nm.     

Development of a targeted adductomic method for the determination of polycyclic aromatic hydrocarbon DNA adducts using online column‐switching liquid chromatography/tandem mass spectrometry

Human exposure to polycyclic aromatic hydrocarbons (PAHs) from sources such as industrial or urban air pollution, tobacco smoke and cooked food is not confined to a single compound, but instead to mixtures of different PAHs. The interaction of different PAHs may lead to additive, synergistic or antagonistic effects in terms of DNA adduct formation and carcinogenic activity resulting from changes in metabolic activation to reactive intermediates and DNA repair. The development of a targeted DNA adductomic approach using liquid chromatography/tandem mass spectrometry (LC/MS/MS) incorporating software‐based peak picking and integration for the assessment of exposure to mixtures of PAHs is described. For method development PAH‐modified DNA samples were obtained by reaction of the anti‐dihydrodiol epoxide metabolites of benzo[a]pyrene, benzo[b]fluoranthene, dibenzo[a,l]pyrene (DB[a,l]P) and dibenz[a,h]anthracene with calf thymus DNA in vitro and enzymatically hydrolysed to 2′‐deoxynucleosides. Positive LC/electrospray ionisation (ESI)‐MS/MS collision‐induced dissociation product ion spectra data showed that the majority of adducts displayed a common fragmentation for the neutral loss of 116 u (2′‐deoxyribose) resulting in a major product ion derived from the adducted base. The exception was the DB[a,l]P dihydrodiol epoxide adduct of 2′‐deoxyadenosine which resulted in major product ions derived from the PAH moiety being detected. Specific detection of mixtures of PAH‐adducted 2′‐deoxynucleosides was achieved using online column‐switching LC/MS/MS in conjunction with selected reaction monitoring (SRM) of the [M+H]⁺ to [M+H–116]⁺ transition plus product ions derived from the PAH moiety for improved sensitivity of detection and a comparison was made to detection by constant neutral loss scanning. In conclusion, different PAH DNA adducts were detected by employing SRM [M+H–116]⁺ transitions or constant neutral loss scanning. However, for improved sensitivity of detection optimised SRM transitions relating to the PAH moiety product ions are required for certain PAH DNA adducts for the development of targeted DNA adductomic methods. Copyright © 2010 John Wiley & Sons, Ltd.     

trans‐4‐[(4‐Di­methyl­amino­phenyl)­imino­methyl]‐N‐methyl­pyridinium para‐toluene­sulfonate

In the title compound, C₁₅H₁₈N₃⁺·C₇H₇O₃S^?, the phenyl­ene and pyridyl rings are somewhat twisted with respect to each other, forming a dihedral angle of 23.49 (6)°. The compound contains a dipolar chromophoric cation, but crystallizes in the centrosymmetric space group P2₁/n and is thus not expected to display quadratic non‐linear optical effects.     

Sensitivity Enhancement in Nickel Hydroxide/3D‐Graphene as Enzymeless Glucose Detection

A nickel hydroxide (Ni(OH)₂)/3D‐graphene composite is used as monolithic free‐standing electrode for enzymeless electrochemical detection of glucose. Ni(OH)₂ nanoflakes are synthesized by using a simple solution growth procedure on 3D‐graphene foam which was grown by chemical vapor deposition (CVD). The pore structure of 3D‐graphene allows easy access to glucose with high surface area, which leads to glucose detection with an ultrahigh sensitivity of 3.49 mA mM^?1 cm^?2 and a significant lower detection limit up to 24 nM. Cyclic voltammetry (CV) and potentionstatic mode is used for non‐enzymatic glucose sensing. The impedance and effective surface area have been studied well. The high sensitivity, low detection limit and simple configuration of Ni(OH)₂/three dimensional (3D)‐graphene composite electrodes can evoke its industrial application in glucose sensing devices.     

Structural and Spectroscopic Characterization of a High‐Spin {FeNO}6 Complex with an Iron(IV)−NO− Electronic Structure

Although the interaction of low‐spin ferric complexes with nitric oxide has been well studied, examples of stable high‐spin ferric nitrosyls (such as those that could be expected to form at typical non‐heme iron sites in biology) are extremely rare. Using the TMG₃tren co‐ligand, we have prepared a high‐spin ferric NO adduct ({FeNO}⁶ complex) via electrochemical or chemical oxidation of the corresponding high‐spin ferrous NO {FeNO}⁷ complex. The {FeNO}⁶ compound is characterized by UV/Visible and IR spectroelectrochemistry, Mössbauer and NMR spectroscopy, X‐ray crystallography, and DFT calculations. The data show that its electronic structure is best described as a high‐spin iron(IV) center bound to a triplet NO^? ligand with a very covalent iron?NO bond. This finding demonstrates that this high‐spin iron nitrosyl compound undergoes iron‐centered redox chemistry, leading to fundamentally different properties than corresponding low‐spin compounds, which undergo NO‐centered redox transformations.     

AFM‐Correlated CSM‐Coupled Raman/Fluorescence Studies on Selective Interactions of Water Soluble Porphyrins with DNA

The Raman and fluorescence spectroscopic properties of water‐soluble oxo‐titanium(IV) mesotetrakis (1‐methyl pyridium‐4‐yl) porphyrin (O=Ti(TMPyP)⁴⁺) bound with calf thymus DNA and artificial DNAs such as double stranded poly[d(A‐T)₂] and poly[d(G‐C)₂] have been investigated on the single DNA molecule basis by AFM‐correlated confocal scanning microscope (CSM)‐coupled Raman and fluorescence spectroscopic techniques as well as the ensemble‐averaged spectroscopy. The ensemble‐averaged spectroscopic studies imply that the porphyrin interacts with DNA in different groove binding patterns depending on the base pairs. AFM‐images of the different DNAs bound with O=Ti(TMPyP)⁴⁺ were measured, and their morphologies are found to depend on kind of base pairs interacting with O=Ti(TMPyP)⁴⁺. Being correlated with the AFM images, the CSM‐coupled Raman and fluorescence spectral properties of the three different single O=Ti(TMPyP)⁴⁺‐DNA complexes were observed to be highly resolved and sensitive to base pair‐dependent axial ligation of Ti‐O bond as compared to the corresponding ensemble‐averaged spectral properties, which affect the groove binding and its strength of the O=Ti(TMPyP)⁴⁺ with DNA. The axial ligation was found to be accompanied by vibration structural change of the porphyrin ring, leading to keep the shape of double stranded poly[d(A‐T)₂] rigid while poly‐[d(G‐C)₂] and calf thymus DNA flexible after binding with the oxo‐titanyl porphyrin. The base pair dependence of the fluorescence decay times of the DNA‐bound porphyrins was also observed, implying that an excited‐state charge transfer takes place in the G‐C rich major groove in calf thymus DNA. These results suggest that binding of O=Ti(TMPyP)⁴⁺ is more preferential with the G‐C rich major groove than with the A‐T rich minor groove in calf thymus DNA so that the morphology of DNA is changed.