\r\n\tBoth diagnosis and clinical manipulation of the patient with vasospasm is a unique and challenging situation. Multi-clinical approach is extremely mandatory. The patient must be treated in a center, which requires a experienced team with both neurological surgeons, interventional radiologists, neurologists and neuroanesthesiologists. Moreover, a well-equiped, isolated neurointensive care is needed for all patients suffering form subarachnoid hemorraghe.
\r\n\tIn their daily practice, both neurological surgeons, interventional radiologists, neurologists, neuroanesthesiologists, and even intensive care providers have to deal and challenge of vasospasm. Numerous studies relevant to pathophysiological mechanisms underlying vasospasm had been published, but we still know little about the exact mechanisms causing vasospasm. In the last decades of modern medical era, despite the technological developments concerning the neurological care of the patients with vasospasm, we still have no effective treatment and preventive care of this devastating entity.
\r\n\tThe aim of this book project is to provide in detailed knowledge to both physicians and scientists dealing with cerebral vasospasm. This book will attract interest of both students, residents, specialists and academics of neurological sciences.
Derived from the Greek prefix hypo (under) and spadon (gap, cleft), the word hypospadias refers to a congenital condition in which the urethral meatus appears proximal to its usual location at the tip of the penis.
The urethral orifice may lie at any level on the embryologic dorsal1 surface of penis, scrotum or even perineum. The foreskin lacks an inferior portion in a way that the remaining semi‐circumferential tissue resembles of a hood. The glans itself may be slightly flattened. Moreover, many cases of hypospadias may present with a curvature named chordee (from Latin chorda, string) between glans and meatus. This chordee is usually produced by an excess of fibrous tissue.
In order to evaluate the location of the urethral meatus, it should be examined under mild retraction of the foreskin and the skin surrounding the orifice. Though there is no total consensus, most urological texts describe the level of the urethral meatus as follows (Figure 1):
Classification of hypospadias according to level of the urethral meatus.
Distal or anterior (glandular and coronal)
Middle (penile)
Proximal or posterior (penoscrotal, scrotal and perineal).
All observations should include the degree of curvature. This is usually expressed by the angle between the main axis from basis and the main axis from the apex of the glans (Figure 2).
Measurement of the angle of penile curvature.
Most historical studies [1, 2, 3] refer to Heliodorus and Antyllus, two alexandrine surgeons who proposed total amputation of the penis distal to the orifice. The first description of hypospadias, however, is attributed to Galen (129‐ca.199 AD). Several isolated observations and treatment proposals followed along the next centuries. The Portuguese Amatus Lusitanus (1511–1568) is usually credited as the first to carve a tunnel between the glans and the ectopical meatus. An illustrious patient was King Henry II of France, who presented with a chordee and underwent some kind of procedure in the hands of royal surgeon Jean Fernel. During the eighteenth century, Morgagni compared the condition to the penile groove of turtles and questioned an association between hypospadias and infertility.
The bulk of current techniques derive from conceptual improvements of the nineteenth century. Bouisson proposed a scrotal skin flap to create the inferior wall of the missing urethral segment in 1861. In 1869, Thiersch described tubularised skin grafts as a means to create a neourethra in epispadias (another unrelated urethral malformation). In 1874, Théophile Anger adapted this technique to obtain a successful correction of a penoscrotal hypospadias. In 1880, Duplay described a two‐stage repair that included the correction of chordee as the first stage and the urethral reconstruction by means of local flaps from the penile ventral skin as a second stage. Nove‐Josserand was the first surgeon to describe free skin grafts to create a neourethra in scrotal hypospadias in 1897.
Former milestones to be cited usually include the works by Matthieu (a flap from proximal skin with parallel sutured lines, 1932), Nesbitt (a technique to treat congenital curvature using fundoplication of the tunica albuginea, 1941), Mustardé (a large flap of perimeatal skin combined with a ‘V’ incision of the glans, 1965), Duckett [Meatal advancement and glanuloplasty (MAGPI) procedure—1981], Koyanagi (a technique for the more complex scrotal cases, 1984) and Snodgrass (an incision of the tubularised urethral plate, 1994). A great number of surgeons have contributed to this field in order to achieve an acceptable correction to any kind of hypospadias and any claim for ‘a new concept’ is difficult to prove.
Hypospadias is a common congenital malformation. A nationwide study from Taiwan [4] for the period from 1997 to 2008 has shown a mean incidence of 3.38 per 1000 live male births. A recent series from Sweden [5] has shown an increase from 4.5 cases per 1000 live male births (1973–1989) to 8 per 1000 live male births (1990–2009).
Fortunately, there is a higher incidence of the less severe variants of the condition. Thus, a Dutch series [6] has shown how 59% of hypospadias are anterior (glanular and coronal), 29% are middle (penile) and 12% are posterior (penoscrotal, scrotal and perineal).
Urethral closing is controlled by androgen receptors that bind to dihydrotestosterone. 5‐alpha reductase II catalyses the conversion from testosterone to dihydrotestosterone. Most authors mention a multifactorial aetiology and a putative influence on genes that control androgen metabolism. Endocrine disruptors as anti‐androgenic substances, hormones or environmental pollutants are heavily suspected as important factors in the pathogenesis of hypospadias in the prenatal period [7]. It is difficult to extrapolate the findings from animals to human beings, however.
Though some genes have been pointed out as causative factors of hypospadias, not many of them have been examined to the point of allowing unequivocal conclusions. There are contradicting studies about the effects of particular drugs on humans, such as the anti‐epileptic valproate or the anti‐hystaminic loratadine [8].
Hypospadias is more frequent among children of men who themselves have had hypospadias. The risk also rises for the brothers of children with hypospadias [9, 10].
Undescended testis in variable degrees and inguinal hernia are the most common anomalies seen in boys with hypospadias. The more proximal the hypospadias, the more frequent these anomalies.
Diverticula of the prostatic portion of the urethra are seen in severe proximal forms. Infection is a frequent complication of this kind of diverticula and is usually addressed with antibiotic treatment. However, some centres still advise routine explorations of the upper urinary tract in proximal forms [11].
Discovery of intersex states is extremely rare but a karyotype is recommended in case of total cryptorchidism, micropenis, penoscrotal transposition (PST) or biphid scrotum [12].
Imperforate anus and myelomeningocele may be associated with hypospadias. Finally, hypospadias may be part of some complex entities such as McKusick‐Kaufman syndrome, Brachmann‐de Lange syndrome, Fryns syndrome, Pallister‐Hall syndrome, Smith‐Lemli‐Opitz syndrome, Rapp‐Hodgkin syndrome, Marden‐Walker syndrome or fronto‐facio‐nasal dysplasia [13].
Technical advances allow operating earlier than in previous decades. Many surgeons advocate intervening in the first 2 years of life for minor distal forms. On the other hand, because increased penile size minimises the risk of producing undesired damage, complicated proximal forms are usually postponed. There is broad consensus to have all procedures done before compulsory school age at 4–5 years with the aim of avoiding psychosocial issues as bullying and comparison with peers [14].
Most surgeons think of magnification loupes as a minimal requisite for this kind of surgery; some of them even favour the use of the surgical microscope. Magnification makes the surgeon aware of the importance of minor vessels. In any case, it minimises the rate of complications and it is indispensable in infants and toddlers.
Many of the instruments used in hypospadias surgery (Castroviejo needle holders, palpebral retractors, microsurgical pincettes) are similar to the ones used in ophthalmic surgery. Depending on centres and individuals, there are some variations but most surgeons apply absorbable polyglactin, polyglycolic acid or monofilament polydioxanone sutures for closing of the neourethra. Nylon or polypropylene are only used in skin sutures and removed after 10–14 days. Surgical calibre of these materials usually varies between 5/0 and 7/0.
Introduced in the 1970s [15], the injection of saline solution facilitates correct appreciation of the chordee during the procedure. Some surgeons use it as an ancillary diagnostic procedure before planning an ultimate corrective operation.
Also starting in the 1970s [16], several techniques have been described to add an extra protective layer of tissue: de‐epithelised skin, external spermatic fascia, Buck’s fascia, tunica vaginalis or most usually dartos fascia flaps. These procedures decrease significatively the rate of postoperative fistulas [17]. Mobilisation of the dartos muscle over the repair allows ‘waterproofing’. Some surgeons use fibrin glue before suturing the final skin layer.
As a precaution to prevent undesired burns of the thin penile structures, most surgeons favour bipolar diathermy.
It is generally accepted that using a transient tourniquet to operate in an almost bloodless field eases visualisation and shortens procedure time. (Needless to say, the surgical team must pay attention not to forget tourniquet removal before dressing at the end of the operation.)
A penile block before the end of the operation, using bupivacaine, diminishes pain and the risk of dangerous manipulations of the dressing. Moreover, due to the extensive use of penile block, some minor procedures can be performed as ambulatory day‐surgery.
Catheters divert the pressure on the suture zone during the immediate postoperative period. They allow bladder voiding in case of clotting or spasm. As they should be least reactive, silicone is the most favoured catheter or stent material. Catheters and stents provide a priceless protection in middle and proximal hypospadias. Bladder spasm can be reduced by using oxybutynin.
Confection of a mildly compressive dressing deserves special attention at the end of the procedure. A certain degree of pressure is needed to maintain haemostasis and diminish local oedema. A modern trend promotes abstention of any kind of dressing [18]. In any case, all eventual dressings should be non‐adhesive to prevent unwanted tearing at the moment of removal.
More than 300 techniques have been described for the correction of the diverse types of hypospadias. This great number probably reflects that no single technique can provide an answer to all situations. The average hypospadias surgeon concentrates on mastering a basic arsenal with a certain number of flexible options. Complicated presentations may need complex grafts of mucosa collected from the bladder (introduced by Memmelaar in 1947 [19]) or buccal cavity (first performed by Sapezhko in the nineteenth century [20]).
Correction of chordee should precede any hypospadias surgery to estimate the real length of the straightened urethra (Figure 3). A common classification includes four types. Type I is an ‘easy’ skin tethering. Type II includes a fibrotic fascia. Type III involves corporal disproportion. Type IV consists of a true urethral tethering [21]. The chordee may appear isolated without hypospadias. All fibrous vestiges running along the penile shaft from glans to meatus must be carefully dissected to avoid damage to the urethral plate and the cavernous bodies. Many surgeons prefer a two‐stage repair in cases of hypospadias with severe chordee.
Dissection of a chordee without hypospadias.
The MAGPI technique was described by Duckett in 1981 [22]. It may be useful in the more distal types of hypospadias without chordee that present good skin quality. After liberating the ventral skin, the surgeon performs a triangular suprameatal incision from the point where the new meatus is intended. The centre of the hypospadic meatus is sutured to the vertex of the triangle in order to achieve ascension. The preputial frenulum is simulated by suturing in an inverted ‘V’, the edges of the missing balanopreputial groove (Figure 4).
The initial stage and four different phases in the MAGPI technique.
Though described by Mathieu in 1932 [23], it bears a strong resemblance to previous operations and has undergone subtle modifications and refinements by surgeons as Gibbons, Devine, Horton, Barcat or van der Meulen to adapt to diverse situations. When the meatus lies subcoronal (or even in the most distal third of the penile shaft), this technique uses a flap of the perimeatal skin to create the missing wall of the urethra in a tubularised way (Figure 5).
The Mathieu technique.
As described in 1955 [24], this technique is still used on penoscrotal or proximal third types. It is inspired by the concepts of Thiersch and Duplay. The incised edges of the open urethral plate are sewn together and tubularised (Figure 6). As usual, there are many variations to this technique.
Different stages of the Byars procedure.
Warren Snodgrass introduced a substantial variation [25] that is now becoming the most usual procedure in any kind of hypospadias. He proposed a longitudinal incision of the urethral plate all along the midline. This incision allows easier approaching of the edges of the open urethral plate (Figure 7).
Longitudinal transection of the urethral plate in the Snodgrass procedure.
These are delicate procedures that involve the crafting of a new urethra by using the foreskin [26, 27]. The vascularisation of the preputial flap stems from the basis of the penis and must be preserved to avoid flap necrosis and failure (Figure 8). The size of the flap is precisely measured having in sight an undesired retraction (when too short) or diverticula (when too wide). There are different available options for the pedicle.
Different stages in the Duckett island flap procedure.
Penoscrotal transposition (PST) represents a rare congenital abnormality of external genitalia in which the scrotum is positioned superiorly or anteriorly in relation to the penis (Figure 9). It includes a large spectrum of anomalies, ranging from the mild bifid scrotum form to the complete penoscrotal transposition (CPST) where the scrotum is located cephalic to the penis [28].
A moderate degree of complete penoscrotal transposition.
Usually patients present other associated anomalies. Hypospadias, chordee and renal dysplasia as well as anal abnormalities are frequently associated in most patients. Cardiac, gastrointestinal, craniofacial, skeletal and central nervous system malformations have to be ruled out in most severe cases of CPST. Aetiology remains uncertain. A genetic background finds the largest consensus in literature. It is probably linked to an abnormal genital tubercle development around the fifth to sixth week of gestation which might affect the migration and fusion of the scrotum.
Prenatal diagnosis of PST is difficult but it should be considered in the differential diagnosis when ambiguous genitalia or a major urogenital abnormality is suspected on the ultrasound [29].
Surgical correction is challenging and is usually performed around the 15th–18th month of birth. The size of the phallus and its potential to develop into a sexually satisfactory penis at puberty should be carefully evaluated before surgery. Reassignment to female gender may even be a prudent therapeutic option in a small number of extreme penoscrotal transposition cases due to the unsatisfactory results obtained with penile repositioning and reconstruction [30].
Repairs of penoscrotal transposition rely on the creation of rotational flaps to mobilise the scrotum downwards or transpose the penis to a neo meatus created in the skin of the mons pubis. All procedures entail a complete circular incision around the root of the penis. This usually results in severe and massive oedema of the penile skin, which delays correction of the associated hypospadias and increases the incidence of complications. The skin vascularity and lymphatics may be impaired by the designed incision.
Several surgical techniques are described in the literature for the incomplete PST. The modified Glenn‐Anderson [31] techniques are commonly used. In these techniques, the two halves of the scrotum are completely mobilised as a rotational flap and relocated in the right position. The penis can be transposed to a neo hole created in the skin of the mons pubis. To reduce the incidence of oedema of the penile skin consequent upon a circular incision around the root of the penis, Saleh suggests to maintain the penile skin connected to the skin of the lower abdomen by a small strip of skin (Figure 10); thus, aids in obtaining a good outcome [32].
Design of scrotal flaps in a modified Glenn‐Anderson procedure.
Many years ago, operating on hypospadias was said to be a sure way to ruin one’s reputation in a paediatric department. Complications such as fistulas are unavoidable but fortunately there is remarkable improvement in this area when the above‐mentioned general principles are routinely applied [33, 34]. Diverticula are less frequent when appropriate planning is carried out. Skin flap (or even glans!) necrosis and persistent chordee are becoming very rare complications.
Perioperative antibiotics may help to reduce the risk of infection, especially with indwelling catheters and adult patients.
Usually, it may be prevented with appropriate dressings and non‐adherent materials. Instructing the parents and a correct postoperative analgesia would prevent the child to scrub the area.
Urethrocutaneous fistulas arise from the suture line of the crafted neourethra in all series but their proportion is reported to be from 3 to 20%. Fortunately, this incidence is far from the high values (as much as 45%) observed 40 years ago [35, 36]. Higher fistulisation rates are observed after tubulised free grafts. The most common causes of fistulisation include ischaemia, infection, intolerance to the suture material, distal obstruction to the urine outflow and poor surgical technique. Most teams prefer a waiting period of 6 months before any reoperation. A little number of small early fistulas seems to heal spontaneously. When repairing a fistula, a well‐vascularised layer should cover the area (Figure 11).
Closing of urethral fistula with a rotating flap.
Most cases of narrow urethra may be treated by dilation in the first preoperative months. Complicated cases may require a new operation that may involve mucosal grafts.
Nitrogen-containing heterocyclic compounds are indispensable for life as they are part of essential building blocks like amino acids, nucleotides, etc. 1,2,3-Triazoles are one of the most important nitrogen-containing five-membered heterocycles and have a wide range of applications in pharmaceuticals, supramolecular chemistry, organic synthesis, chemical biology and industry [1, 2, 3, 4, 5, 6]. The 1,2,3-triazoles has numerous useful properties like high chemical stability (usually inert to acidic or basic hydrolysis as well as oxidizing and reducing conditions even at high temperature), aromatic character, strong dipole moment (4.8–5.6 Debye), and hydrogen bonding ability [7]. These spectacular features make the substituted 1,2,3-triazole motif structurally resembling to the amide bond, mimicking an E or a Z amide bond. Many prominent medicinal compounds having a 1,2,3-triazole core are available in the market like anticonvulsant drug Rufinamide, broad spectrum cephalosporin antibiotic cefatrizine, an anticancer drug carboxyamidotriazole and
Owing to its versatile applications, the synthesis of 1,2,3-triazoles has been a subject of extensive research. The synthetic methodologies for the preparation of this important scaffold can be broadly divided into four categories (Figure 1) [9]:
Huisgen 1,3-dipolar cycloaddition
Metal-catalyzed 1,3-dipolar cycloaddition
Strain-promoted azide alkyne cycloaddition
Metal-free synthesis of 1,2,3-triazoles
Strategy of the synthesis of 1,2,3-triazoles.
Huisgen 1,3-dipolar cycloaddition was the most straightforward and atom-economical synthesis of 1,2,3-triazoles. However, elevated reaction temperature and poor regioselectivity (mixtures of 1,4- and 1,5-isomers) make this process unsatisfactory [10].
In 2001, Sharpless et al. coined the term “Click Chemistry,” a set of highly reliable, practical, and selective reactions for the rapid synthesis of valuable new compounds and combinatorial libraries. The click reaction should be modular, with high yield, wide in scope, generate only innocuous by-products (that can be removed without chromatography), stereospecific, easy to carry out and that need benign solvent [11]. In 2002, the groups of Sharpless and Meldal independently revealed a copper-catalyzed variant of Huisgen’s azide-alkyne cycloaddition (CuAAC reaction) identified as one of the prime example of click chemistry in the literature [12, 13]. The unique advantages of CuAAC reaction are excellent substrate scope, prominent atom economy, good regioselectivity (only 1,4-isomer), high yield of products and mild reaction conditions [14, 15, 16, 17].
In 2005, Fokin and coworkers devised an efficient approach for the construction of 1,5-disubstituted 1,2,3-triazoles by ruthenium cyclopentadienyl complexes (RuAAC). In addition, internal alkynes also effective in this protocol leading to fully substituted 1,2,3-triazoles [18].
The McNulty group reported a well-defined Ag(I) complex for the regioselective synthesis of 1,4-disubstituted 1,2,3-triazoles at room temperature [19].
An interesting Zn(OAc)2-catalyzed azide-alkyne cycloaddition was developed by Postnikov and his research group affording 1,4-disubstituted 1,2,3-triazoles [20].
In 2017, Kim et al. devised Cp2Ni/Xantphos catalytic method to access 1,5-disubstituted 1,2,3-triazoles under mild condition [21].
Sun and coworkers reported intermolecular iridium-catalyzed azide-alkyne cycloaddition reaction (IrAAC) of electron-rich internal alkynes [22].
Despite the overwhelming popularity of click chemistry in modern science and technology, the using of metals creates serious concern in biological system due to cellular toxicity. The Bertozzi group explored an interesting protocol of strain-promoted azide-alkyne cycloaddition (SPAAC) reaction for bioconjugation. The driving force for this reaction was the release of large ring strain in the cycloalkynes which proceeds under physiological condition without any catalyst [23].
Organocatalytic reactions has gained considerable attention in the synthesis of 1,2,3-triazoles using enamines, enolates as dipolarophiles. Besides, activated alkenes were established as a useful substrate for triazole formation.
Ramachary and coworkers developed L-proline-catalyzed synthesis of 1,2,3-triazoles via an enamine mediated [3 + 2]-cycloaddition reaction [24].
In 2011, the regioselective synthesis of 1,4,5-trisubstituted 1,2,3-triazoles was achieved by Wang et al. using an organocatalytic enamine azide reaction [25].
The Bressy group reported synthesis of substituted 1,2,3-triazoles from unactivated ketone and aromatic azide using microwave condition [26].
Wang and coworkers devised an organocatalytic method for the preparation of fully substituted 1,2,3-triazoles by diethylamine-catalyzed reaction of azides and allyl ketones [27].
Iodine mediated, oxidant free synthesis of 1,5-disubstituted 1,2,3-triazoles was reported by the Wan group using primary amines, enamines and tosylhydrazine [28].
Using potassium carbonate, Kannan and co-workers developed a protocol for the synthesis of 4-acetyl-5-methyl-1,2,3-triazoles from acetylacetone and aromatic azides [29].
The Ramachary group described an efficient methodology for the preparation of 1,4-disubstituted 1,2,3-triazoles using organocatalytic azide-aldehyde [3 + 2] cycloaddition reaction [30].
Paixão et al. reported the use of alkylidenemalononitriles in 1,3-dipolar cycloaddition with aromatic azides mediated by DBU [31].
In their another pioneering work, Ramachary and coworkers reported an interesting organocatalytic [3 + 2]-cycloaddition reaction of ketones with azides for synthesis of fully substituted 1,2,3-triazoles [32].
In a methodology published in 1986, Sakai et al. used primary amines and α,α-dichloro ketone derived tosylhydrazones for the metal free synthesis of 1,2,3-triazoles [33].
Westermann and co-workers developed a cascade reaction using α,α-dichlorotosylhydrazones and primary amines in the presence of diisopropylethylamine [34].
Metal free regioselective synthesis of 1,4,5-trisubstituted 1,2,3-triazoles was reported by Dehaen et al. from aldehydes, nitroalkanes and organic azides [35].
The Guan group developed p-toluenesulfonic acid-catalyzed 1,3-dipolar cycloaddition reaction for the synthesis of 4-aryl-NH-1,2,3-triazoles from nitroolefins with sodium azide [36].
1,2,3-triazoles are stable towards metabolic degradation and easily form hydrogen bonding which can increase solubility favoring the binding of biomolecular targets. Owing to their unique properties, 1,2,3-triazoles are attractive building blocks in drug discovery.
Cancer is a major public health concern and second leading cause of mortality globally. Despite that numerous anticancer agents including taxol, vincristine, vinblastine, camptothecin derivatives, topotecan are available, search for novel compounds with different modes of actions has received significant interest.
Kallander et al. reported 4-aryl-1,2,3-triazoles 1 as inhibitors of human methionine aminopeptidase type 2 (hMetAP2). The anticancer activity of these molecules is due to the N1 and N2 nitrogen atoms of the triazole moiety that actively contribute in binding to the active site of enzyme [37].
Odlo and coworkers disclosed a series of cis-restricted 1,5-disubstituted 1,2,3-triazole analogues of combretastatin A-4. One of the triazole derivatives 2 showed effective cytotoxic activity against various cancer cell lines with IC50 values in the nanomolar range. Molecular docking study shows that the triazole moiety interacts with β-tubulin via H-bonding with numerous amino acids [38].
The series of triazole-modified 20,30-dideoxy-20,30-diethanethioribonucleosides 3 displayed considerably better antitumor activity towards HepG2, A549, and Hela cell lines and higher cytotoxicity towards HepG2, LAC, and Hela cell lines compared to the control drug floxuridine [39].
Rangappa and coworkers prepared a series of 1,2-benzisoxazole tethered 1,2,3-triazoles 4 and established its noteworthy antiproliferative effect against human acute myeloid leukemia (AML) cells. Using MTT assay, 3-(4-(4-phenoxyphenyl)-1H-1,2,3-triazol-1-yl)benzo[d]isoxazole was found to be the most potent antiproliferative agent with an
Using “click chemistry” approach, the Miller group prepared a series of N-((1-benzyl-1H-1,2,3-triazol-4-yl)methyl)arylamides and examined their antiproliferative activity. One of the compound 5 displayed an
Lin and coworkers synthesized a series of heterocycle-fused 1,2,3-triazoles and evaluated their cytotoxic activity. With IC50 values lower than
1,2,3-triazole derivatives of betulinic acid were synthesized by Koul et al. and their cytotoxic activity against nine human cancer cell lines was evaluated (Figure 2). Two molecules 7 and 8 exhibited notable
Some examples of 1,2,3-triazole containing molecules with anticancer activity.
Inflammation is particularly complex biological process of body tissues, where membrane-bound phospholipids release arachidonic acid (AA), followed by biotransformation processes using cycloxygenase (COX) and 5-lipoxygenase (5-LOX) pathways. Several non-steroidal anti-inflammatory drugs (NSAIDs) such as indomethacin, ibuprofen, and naproxen block arachidonic acid metabolism by obstructing cycloxygenase. Nevertheless the side effects associated with these drugs prompted medicinal chemists to develop alternative scaffolds.
The Jung group synthesized twenty-four phenyl-1H-1,2,3-triazole derivatives and studied their biological activity. At the same dose of 25 mg/kg, compound 9 showed more compelling effects than the existing anti-inflammatory drug diclofenac [44].
Yar and coworkers reported 1,2,3-triazole tethered Indole-3-glyoxamide derivatives for in vivo anti-inflammatory activity using click chemistry approach. Two compounds 10 and 11 displayed excellent inhibition of COX-2 (
Various examples of 1,2,3-triazole containing molecules with anti-inflammatory activity.
Tuberculosis (TB) caused by Mycobacterium tuberculosis is one of the infectious contagious disease and remains a serious risk to public health worldwide. Generally, the direct observed therapy strategy (DOTS) is the treatment for TB, but the emergence of multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) developed challenges. Therefore identifying of effective anti-TB drug candidates has received enormous interest.
Labadie and coworkers used click chemistry to synthesize a small library of 1,2,3-triazole derivatives and screened them against Mycobacterium tuberculosis and Mycobacterium avium. The biological screening indicated that the triazole 12 displayed more significant activity against M. tuberculosis than standard drug [46].
Using click chemistry, the Boechat group reported 4-substituted N-phenyl-1,2,3-triazole derivatives for antimicrobial activity against Mycobacterium tuberculosis strain H37Rv (ATCC 27294). Derivatives of isoniazid, (E)-N′-[(1-aryl)-1H-1,2,3-triazole-4-yl)methylene] isonicotinoyl hydrazides, 13 revealed significant activity with minimum inhibitory concentration (MIC) value of
The Kantevari group described a molecular hybridization approach for the synthesis of triazole clubbed dibenzo[b,d]thiophene-based Mycobacterium tuberculosis inhibitors. The most potent compounds 14 and 15 in check of their in vitro activity against M. tuberculosis strain H37Rv exhibited
Zhang et al. synthesized triazole-based library of benzofuran salicylic acid derivatives using click chemistry strategy. The compound 16 was found to be potent antiTB therapeutic with efficient cellular activity (Figure 4) [49].
Representative examples of 1,2,3-triazole containing molecules with antitubercular activity.
Fungal and bacterial infections create severe apprehension for human and animal survival. The inefficacy of available drugs and rising resistant strains demand significant interest into new classes of antimicrobial agents.
Agarwal and coworkers synthesized 1,2,3-triazole derivatives of chalcones and flavones by click chemistry and screened their antimicrobial and antiplasmodial activity. Several compound including 17 showed promising antifungal and antibacterial activity [50].
The Murugulla group studied antimicrobial activity of theophylline containing 1,2,3-triazoles with variant nucleoside derivatives. Compound 18 was shown to be potent and effective against three bacterial strains B. cereus, Escherichia coli and P. aureoginosa with MIC values of 0.0156, 0.03125, 0.0625 mg/mL and compound 19 with MIC values of 0.03125, 0.0156, 0.0625 mg/mL was found to be effective against S. aureus, B. cereus and Escherichia coli, respectively [51].
Diaryl sulfone containing novel 1,2,3-triazoles were synthesized by Jørgensen and coworkers and their biological evaluation was carried out as well. Compound 20 was found to be the most potent antifungal agents with MIC at
Zhou et al. reported a series of 1,2,3-triazole-derived naphthalimides for potential antimicrobial activity. Bioactive assay revealed that 21 showed better anti-Escherichia coli activity than existing drugs Norfloxacin and Chloromycin [53].
5-nitrofuran—triazole congener—was prepared by the Kamal group and its biological activity was studied. Among the other compounds, 22 exhibited promising antibacterial activity (MIC value of
Representative examples of 1,2,3-triazole containing molecules with antimicrobial activity.
Viral diseases are caused by viruses infecting an organism body. Although vaccines and antiviral drugs are used for treating viral infections, advance of novel viruses creates health risk over the world. Therefore development of alternative antiviral agents is of significant interest.
Boechat and coworkers reported the synthesis of 1,2,3-triazole nucleoside ribavirin analogs and studied their antiviral activity. The synthesized compound 23 displayed potent activity with
Ribavirin analogues—4,5-disubstituted 1,2,3-triazole nucleosides—were synthesized by Zeidler et al. and screened for their biological activity. 5-ethynyl nucleoside 24 exhibited effective virus-inhibitory activity against influenza A (H1N1, H3N2 and H5N1), influenza B, measles and respiratory syncytial viruses [56].
The Ding group targeted virus nucleoprotein and synthesized 1,2,3-triazole-4-carboxamide derivatives for anti-influenza drug development. The compound 25, inhibited the replication of various H3N2 and H1N1 influenza A virus strains with IC50 values ranging from 0.5 to 4.6 μM (Figure 6) [57].
Examples of 1,2,3-triazole containing molecules with antiviral activity.
In summary, 1,2,3-triazole moiety has proven to be a privileged scaffolds in medicinal chemistry. The exceptional properties of this promising heterocycle facilitate its wide range of applications from material science to bioconjugation. Thanks to Sharpless for introducing “Click Chemistry,” one of the most prevailing tools in drug discovery, chemical biology, and proteomic applications and undoubtedly opens new avenue to the scientific community towards the improvement of life.
The author is thankful for the financial support by CSIR, New Delhi, India.
There are no conflicts to declare.
IntechOpen aims to ensure that original material is published while at the same time giving significant freedom to our Authors. To that end we maintain a flexible Copyright Policy guaranteeing that there is no transfer of copyright to the publisher and Authors retain exclusive copyright to their Work.
',metaTitle:"Publication Agreement - Chapters",metaDescription:"IN TECH aims to guarantee that original material is published while at the same time giving significant freedom to our authors. For that matter, we uphold a flexible copyright policy meaning that there is no transfer of copyright to the publisher and authors retain exclusive copyright to their work.\n\nWhen submitting a manuscript the Corresponding Author is required to accept the terms and conditions set forth in our Publication Agreement as follows:",metaKeywords:null,canonicalURL:"/page/publication-agreement-chapters",contentRaw:'[{"type":"htmlEditorComponent","content":"The Corresponding Author (acting on behalf of all Authors) and INTECHOPEN LIMITED, incorporated and registered in England and Wales with company number 11086078 and a registered office at 5 Princes Gate Court, London, United Kingdom, SW7 2QJ conclude the following Agreement regarding the publication of a Book Chapter:
\\n\\n1. DEFINITIONS
\\n\\nCorresponding Author: The Author of the Chapter who serves as a Signatory to this Agreement. The Corresponding Author acts on behalf of any other Co-Author.
\\n\\nCo-Author: All other Authors of the Chapter besides the Corresponding Author.
\\n\\nIntechOpen: IntechOpen Ltd., the Publisher of the Book.
\\n\\nBook: The publication as a collection of chapters compiled by IntechOpen including the Chapter. Chapter: The original literary work created by Corresponding Author and any Co-Author that is the subject of this Agreement.
\\n\\n2. CORRESPONDING AUTHOR'S GRANT OF RIGHTS
\\n\\n2.1 Subject to the following Article, the Corresponding Author grants and shall ensure that each Co-Author grants, to IntechOpen, during the full term of copyright and any extensions or renewals of that term the following:
\\n\\nThe aforementioned licenses shall survive the expiry or termination of this Agreement for any reason.
\\n\\n2.2 The Corresponding Author (on their own behalf and on behalf of any Co-Author) reserves the following rights to the Chapter but agrees not to exercise them in such a way as to adversely affect IntechOpen's ability to utilize the full benefit of this Publication Agreement: (i) reprographic rights worldwide, other than those which subsist in the typographical arrangement of the Chapter as published by IntechOpen; and (ii) public lending rights arising under the Public Lending Right Act 1979, as amended from time to time, and any similar rights arising in any part of the world.
\\n\\nThe Corresponding Author confirms that they (and any Co-Author) are and will remain a member of any applicable licensing and collecting society and any successor to that body responsible for administering royalties for the reprographic reproduction of copyright works.
\\n\\nSubject to the license granted above, copyright in the Chapter and all versions of it created during IntechOpen's editing process (including the published version) is retained by the Corresponding Author and any Co-Author.
\\n\\nSubject to the license granted above, the Corresponding Author and any Co-Author retains patent, trademark and other intellectual property rights to the Chapter.
\\n\\n2.3 All rights granted to IntechOpen in this Article are assignable, sublicensable or otherwise transferrable to third parties without the Corresponding Author's or any Co-Author’s specific approval.
\\n\\n2.4 The Corresponding Author (on their own behalf and on behalf of each Co-Author) will not assert any rights under the Copyright, Designs and Patents Act 1988 to object to derogatory treatment of the Chapter as a consequence of IntechOpen's changes to the Chapter arising from translation of it, corrections and edits for house style, removal of problematic material and other reasonable edits.
\\n\\n3. CORRESPONDING AUTHOR'S DUTIES
\\n\\n3.1 When distributing or re-publishing the Chapter, the Corresponding Author agrees to credit the Book in which the Chapter has been published as the source of first publication, as well as IntechOpen. The Corresponding Author warrants that each Co-Author will also credit the Book in which the Chapter has been published as the source of first publication, as well as IntechOpen, when they are distributing or re-publishing the Chapter.
\\n\\n3.2 When submitting the Chapter, the Corresponding Author agrees to:
\\n\\nThe Corresponding Author will be held responsible for the payment of the Open Access Publishing Fees.
\\n\\nAll payments shall be due 30 days from the date of the issued invoice. The Corresponding Author or the payer on the Corresponding Author's and Co-Authors' behalf will bear all banking and similar charges incurred.
\\n\\n3.3 The Corresponding Author shall obtain in writing all consents necessary for the reproduction of any material in which a third-party right exists, including quotations, photographs and illustrations, in all editions of the Chapter worldwide for the full term of the above licenses, and shall provide to IntechOpen upon request the original copies of such consents for inspection (at IntechOpen's option) or photocopies of such consents.
\\n\\nThe Corresponding Author shall obtain written informed consent for publication from people who might recognize themselves or be identified by others (e.g. from case reports or photographs).
\\n\\n3.4 The Corresponding Author and any Co-Author shall respect confidentiality rights during and after the termination of this Agreement. The information contained in all correspondence and documents as part of the publishing activity between IntechOpen and the Corresponding Author and any Co-Author are confidential and are intended only for the recipient. The contents may not be disclosed publicly and are not intended for unauthorized use or distribution. Any use, disclosure, copying, or distribution is prohibited and may be unlawful.
\\n\\n4. CORRESPONDING AUTHOR'S WARRANTY
\\n\\n4.1 The Corresponding Author represents and warrants that the Chapter does not and will not breach any applicable law or the rights of any third party and, specifically, that the Chapter contains no matter that is defamatory or that infringes any literary or proprietary rights, intellectual property rights, or any rights of privacy. The Corresponding Author warrants and represents that: (i) the Chapter is the original work of themselves and any Co-Author and is not copied wholly or substantially from any other work or material or any other source; (ii) the Chapter has not been formally published in any other peer-reviewed journal or in a book or edited collection, and is not under consideration for any such publication; (iii) they themselves and any Co-Author are qualifying persons under section 154 of the Copyright, Designs and Patents Act 1988; (iv) they themselves and any Co-Author have not assigned and will not during the term of this Publication Agreement purport to assign any of the rights granted to IntechOpen under this Publication Agreement; and (v) the rights granted by this Publication Agreement are free from any security interest, option, mortgage, charge or lien.
\\n\\nThe Corresponding Author also warrants and represents that: (i) they have the full power to enter into this Publication Agreement on their own behalf and on behalf of each Co-Author; and (ii) they have the necessary rights and/or title in and to the Chapter to grant IntechOpen, on behalf of themselves and any Co-Author, the rights and licenses expressed to be granted in this Publication Agreement. If the Chapter was prepared jointly by the Corresponding Author and any Co-Author, the Corresponding Author warrants and represents that: (i) each Co-Author agrees to the submission, license and publication of the Chapter on the terms of this Publication Agreement; and (ii) they have the authority to enter into this Publication Agreement on behalf of and bind each Co-Author. The Corresponding Author shall: (i) ensure each Co-Author complies with all relevant provisions of this Publication Agreement, including those relating to confidentiality, performance and standards, as if a party to this Publication Agreement; and (ii) remain primarily liable for all acts and/or omissions of each such Co-Author.
\\n\\nThe Corresponding Author agrees to indemnify and hold IntechOpen harmless against all liabilities, costs, expenses, damages and losses and all reasonable legal costs and expenses suffered or incurred by IntechOpen arising out of or in connection with any breach of the aforementioned representations and warranties. This indemnity shall not cover IntechOpen to the extent that a claim under it results from IntechOpen's negligence or willful misconduct.
\\n\\n4.2 Nothing in this Publication Agreement shall have the effect of excluding or limiting any liability for death or personal injury caused by negligence or any other liability that cannot be excluded or limited by applicable law.
\\n\\n5. TERMINATION
\\n\\n5.1 IntechOpen has a right to terminate this Publication Agreement for quality, program, technical or other reasons with immediate effect, including without limitation (i) if the Corresponding Author or any Co-Author commits a material breach of this Publication Agreement; (ii) if the Corresponding Author or any Co-Author (being an individual) is the subject of a bankruptcy petition, application or order; or (iii) if the Corresponding Author or any Co-Author (being a company) commences negotiations with all or any class of its creditors with a view to rescheduling any of its debts, or makes a proposal for or enters into any compromise or arrangement with any of its creditors.
\\n\\nIn case of termination, IntechOpen will notify the Corresponding Author, in writing, of the decision.
\\n\\n6. INTECHOPEN’S DUTIES AND RIGHTS
\\n\\n6.1 Unless prevented from doing so by events outside its reasonable control, IntechOpen, in its discretion, agrees to publish the Chapter attributing it to the Corresponding Author and any Co-Author.
\\n\\n6.2 IntechOpen has the right to use the Corresponding Author’s and any Co-Author’s names and likeness in connection with scientific dissemination, retrieval, archiving, web hosting and promotion and marketing of the Chapter and has the right to contact the Corresponding Author and any Co-Author until the Chapter is publicly available on any platform owned and/or operated by IntechOpen.
\\n\\n6.3 IntechOpen is granted the authority to enforce the rights from this Publication Agreement, on behalf of the Corresponding Author and any Co-Author, against third parties (for example in cases of plagiarism or copyright infringements). In respect of any such infringement or suspected infringement of the copyright in the Chapter, IntechOpen shall have absolute discretion in addressing any such infringement which is likely to affect IntechOpen's rights under this Publication Agreement, including issuing and conducting proceedings against the suspected infringer.
\\n\\n7. MISCELLANEOUS
\\n\\n7.1 Further Assurance: The Corresponding Author shall and will ensure that any relevant third party (including any Co-Author) shall, execute and deliver whatever further documents or deeds and perform such acts as IntechOpen reasonably requires from time to time for the purpose of giving IntechOpen the full benefit of the provisions of this Publication Agreement.
\\n\\n7.2 Third Party Rights: A person who is not a party to this Publication Agreement may not enforce any of its provisions under the Contracts (Rights of Third Parties) Act 1999.
\\n\\n7.3 Entire Agreement: This Publication Agreement constitutes the entire agreement between the parties in relation to its subject matter. It replaces and extinguishes all prior agreements, draft agreements, arrangements, collateral warranties, collateral contracts, statements, assurances, representations and undertakings of any nature made by or on behalf of the parties, whether oral or written, in relation to that subject matter. Each party acknowledges that in entering into this Publication Agreement it has not relied upon any oral or written statements, collateral or other warranties, assurances, representations or undertakings which were made by or on behalf of the other party in relation to the subject matter of this Publication Agreement at any time before its signature (together "Pre-Contractual Statements"), other than those which are set out in this Publication Agreement. Each party hereby waives all rights and remedies which might otherwise be available to it in relation to such Pre-Contractual Statements. Nothing in this clause shall exclude or restrict the liability of either party arising out of its pre-contract fraudulent misrepresentation or fraudulent concealment.
\\n\\n7.4 Waiver: No failure or delay by a party to exercise any right or remedy provided under this Publication Agreement or by law shall constitute a waiver of that or any other right or remedy, nor shall it preclude or restrict the further exercise of that or any other right or remedy. No single or partial exercise of such right or remedy shall preclude or restrict the further exercise of that or any other right or remedy.
\\n\\n7.5 Variation: No variation of this Publication Agreement shall be effective unless it is in writing and signed by the parties (or their duly authorized representatives).
\\n\\n7.6 Severance: If any provision or part-provision of this Publication Agreement is or becomes invalid, illegal or unenforceable, it shall be deemed modified to the minimum extent necessary to make it valid, legal and enforceable. If such modification is not possible, the relevant provision or part-provision shall be deemed deleted.
\\n\\nAny modification to or deletion of a provision or part-provision under this clause shall not affect the validity and enforceability of the rest of this Publication Agreement.
\\n\\n7.7 No partnership: Nothing in this Publication Agreement is intended to, or shall be deemed to, establish or create any partnership or joint venture or the relationship of principal and agent or employer and employee between IntechOpen and the Corresponding Author or any Co-Author, nor authorize any party to make or enter into any commitments for or on behalf of any other party.
\\n\\n7.8 Governing law: This Publication Agreement and any dispute or claim (including non-contractual disputes or claims) arising out of or in connection with it or its subject matter or formation shall be governed by and construed in accordance with the law of England and Wales. The parties submit to the exclusive jurisdiction of the English courts to settle any dispute or claim arising out of or in connection with this Publication Agreement (including any non-contractual disputes or claims).
\\n\\nLast updated: 2020-11-27
\\n\\n\\n\\n
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The Corresponding Author (acting on behalf of all Authors) and INTECHOPEN LIMITED, incorporated and registered in England and Wales with company number 11086078 and a registered office at 5 Princes Gate Court, London, United Kingdom, SW7 2QJ conclude the following Agreement regarding the publication of a Book Chapter:
\n\n1. DEFINITIONS
\n\nCorresponding Author: The Author of the Chapter who serves as a Signatory to this Agreement. The Corresponding Author acts on behalf of any other Co-Author.
\n\nCo-Author: All other Authors of the Chapter besides the Corresponding Author.
\n\nIntechOpen: IntechOpen Ltd., the Publisher of the Book.
\n\nBook: The publication as a collection of chapters compiled by IntechOpen including the Chapter. Chapter: The original literary work created by Corresponding Author and any Co-Author that is the subject of this Agreement.
\n\n2. CORRESPONDING AUTHOR'S GRANT OF RIGHTS
\n\n2.1 Subject to the following Article, the Corresponding Author grants and shall ensure that each Co-Author grants, to IntechOpen, during the full term of copyright and any extensions or renewals of that term the following:
\n\nThe aforementioned licenses shall survive the expiry or termination of this Agreement for any reason.
\n\n2.2 The Corresponding Author (on their own behalf and on behalf of any Co-Author) reserves the following rights to the Chapter but agrees not to exercise them in such a way as to adversely affect IntechOpen's ability to utilize the full benefit of this Publication Agreement: (i) reprographic rights worldwide, other than those which subsist in the typographical arrangement of the Chapter as published by IntechOpen; and (ii) public lending rights arising under the Public Lending Right Act 1979, as amended from time to time, and any similar rights arising in any part of the world.
\n\nThe Corresponding Author confirms that they (and any Co-Author) are and will remain a member of any applicable licensing and collecting society and any successor to that body responsible for administering royalties for the reprographic reproduction of copyright works.
\n\nSubject to the license granted above, copyright in the Chapter and all versions of it created during IntechOpen's editing process (including the published version) is retained by the Corresponding Author and any Co-Author.
\n\nSubject to the license granted above, the Corresponding Author and any Co-Author retains patent, trademark and other intellectual property rights to the Chapter.
\n\n2.3 All rights granted to IntechOpen in this Article are assignable, sublicensable or otherwise transferrable to third parties without the Corresponding Author's or any Co-Author’s specific approval.
\n\n2.4 The Corresponding Author (on their own behalf and on behalf of each Co-Author) will not assert any rights under the Copyright, Designs and Patents Act 1988 to object to derogatory treatment of the Chapter as a consequence of IntechOpen's changes to the Chapter arising from translation of it, corrections and edits for house style, removal of problematic material and other reasonable edits.
\n\n3. CORRESPONDING AUTHOR'S DUTIES
\n\n3.1 When distributing or re-publishing the Chapter, the Corresponding Author agrees to credit the Book in which the Chapter has been published as the source of first publication, as well as IntechOpen. The Corresponding Author warrants that each Co-Author will also credit the Book in which the Chapter has been published as the source of first publication, as well as IntechOpen, when they are distributing or re-publishing the Chapter.
\n\n3.2 When submitting the Chapter, the Corresponding Author agrees to:
\n\nThe Corresponding Author will be held responsible for the payment of the Open Access Publishing Fees.
\n\nAll payments shall be due 30 days from the date of the issued invoice. The Corresponding Author or the payer on the Corresponding Author's and Co-Authors' behalf will bear all banking and similar charges incurred.
\n\n3.3 The Corresponding Author shall obtain in writing all consents necessary for the reproduction of any material in which a third-party right exists, including quotations, photographs and illustrations, in all editions of the Chapter worldwide for the full term of the above licenses, and shall provide to IntechOpen upon request the original copies of such consents for inspection (at IntechOpen's option) or photocopies of such consents.
\n\nThe Corresponding Author shall obtain written informed consent for publication from people who might recognize themselves or be identified by others (e.g. from case reports or photographs).
\n\n3.4 The Corresponding Author and any Co-Author shall respect confidentiality rights during and after the termination of this Agreement. The information contained in all correspondence and documents as part of the publishing activity between IntechOpen and the Corresponding Author and any Co-Author are confidential and are intended only for the recipient. The contents may not be disclosed publicly and are not intended for unauthorized use or distribution. Any use, disclosure, copying, or distribution is prohibited and may be unlawful.
\n\n4. CORRESPONDING AUTHOR'S WARRANTY
\n\n4.1 The Corresponding Author represents and warrants that the Chapter does not and will not breach any applicable law or the rights of any third party and, specifically, that the Chapter contains no matter that is defamatory or that infringes any literary or proprietary rights, intellectual property rights, or any rights of privacy. The Corresponding Author warrants and represents that: (i) the Chapter is the original work of themselves and any Co-Author and is not copied wholly or substantially from any other work or material or any other source; (ii) the Chapter has not been formally published in any other peer-reviewed journal or in a book or edited collection, and is not under consideration for any such publication; (iii) they themselves and any Co-Author are qualifying persons under section 154 of the Copyright, Designs and Patents Act 1988; (iv) they themselves and any Co-Author have not assigned and will not during the term of this Publication Agreement purport to assign any of the rights granted to IntechOpen under this Publication Agreement; and (v) the rights granted by this Publication Agreement are free from any security interest, option, mortgage, charge or lien.
\n\nThe Corresponding Author also warrants and represents that: (i) they have the full power to enter into this Publication Agreement on their own behalf and on behalf of each Co-Author; and (ii) they have the necessary rights and/or title in and to the Chapter to grant IntechOpen, on behalf of themselves and any Co-Author, the rights and licenses expressed to be granted in this Publication Agreement. If the Chapter was prepared jointly by the Corresponding Author and any Co-Author, the Corresponding Author warrants and represents that: (i) each Co-Author agrees to the submission, license and publication of the Chapter on the terms of this Publication Agreement; and (ii) they have the authority to enter into this Publication Agreement on behalf of and bind each Co-Author. The Corresponding Author shall: (i) ensure each Co-Author complies with all relevant provisions of this Publication Agreement, including those relating to confidentiality, performance and standards, as if a party to this Publication Agreement; and (ii) remain primarily liable for all acts and/or omissions of each such Co-Author.
\n\nThe Corresponding Author agrees to indemnify and hold IntechOpen harmless against all liabilities, costs, expenses, damages and losses and all reasonable legal costs and expenses suffered or incurred by IntechOpen arising out of or in connection with any breach of the aforementioned representations and warranties. This indemnity shall not cover IntechOpen to the extent that a claim under it results from IntechOpen's negligence or willful misconduct.
\n\n4.2 Nothing in this Publication Agreement shall have the effect of excluding or limiting any liability for death or personal injury caused by negligence or any other liability that cannot be excluded or limited by applicable law.
\n\n5. TERMINATION
\n\n5.1 IntechOpen has a right to terminate this Publication Agreement for quality, program, technical or other reasons with immediate effect, including without limitation (i) if the Corresponding Author or any Co-Author commits a material breach of this Publication Agreement; (ii) if the Corresponding Author or any Co-Author (being an individual) is the subject of a bankruptcy petition, application or order; or (iii) if the Corresponding Author or any Co-Author (being a company) commences negotiations with all or any class of its creditors with a view to rescheduling any of its debts, or makes a proposal for or enters into any compromise or arrangement with any of its creditors.
\n\nIn case of termination, IntechOpen will notify the Corresponding Author, in writing, of the decision.
\n\n6. INTECHOPEN’S DUTIES AND RIGHTS
\n\n6.1 Unless prevented from doing so by events outside its reasonable control, IntechOpen, in its discretion, agrees to publish the Chapter attributing it to the Corresponding Author and any Co-Author.
\n\n6.2 IntechOpen has the right to use the Corresponding Author’s and any Co-Author’s names and likeness in connection with scientific dissemination, retrieval, archiving, web hosting and promotion and marketing of the Chapter and has the right to contact the Corresponding Author and any Co-Author until the Chapter is publicly available on any platform owned and/or operated by IntechOpen.
\n\n6.3 IntechOpen is granted the authority to enforce the rights from this Publication Agreement, on behalf of the Corresponding Author and any Co-Author, against third parties (for example in cases of plagiarism or copyright infringements). In respect of any such infringement or suspected infringement of the copyright in the Chapter, IntechOpen shall have absolute discretion in addressing any such infringement which is likely to affect IntechOpen's rights under this Publication Agreement, including issuing and conducting proceedings against the suspected infringer.
\n\n7. MISCELLANEOUS
\n\n7.1 Further Assurance: The Corresponding Author shall and will ensure that any relevant third party (including any Co-Author) shall, execute and deliver whatever further documents or deeds and perform such acts as IntechOpen reasonably requires from time to time for the purpose of giving IntechOpen the full benefit of the provisions of this Publication Agreement.
\n\n7.2 Third Party Rights: A person who is not a party to this Publication Agreement may not enforce any of its provisions under the Contracts (Rights of Third Parties) Act 1999.
\n\n7.3 Entire Agreement: This Publication Agreement constitutes the entire agreement between the parties in relation to its subject matter. It replaces and extinguishes all prior agreements, draft agreements, arrangements, collateral warranties, collateral contracts, statements, assurances, representations and undertakings of any nature made by or on behalf of the parties, whether oral or written, in relation to that subject matter. Each party acknowledges that in entering into this Publication Agreement it has not relied upon any oral or written statements, collateral or other warranties, assurances, representations or undertakings which were made by or on behalf of the other party in relation to the subject matter of this Publication Agreement at any time before its signature (together "Pre-Contractual Statements"), other than those which are set out in this Publication Agreement. Each party hereby waives all rights and remedies which might otherwise be available to it in relation to such Pre-Contractual Statements. Nothing in this clause shall exclude or restrict the liability of either party arising out of its pre-contract fraudulent misrepresentation or fraudulent concealment.
\n\n7.4 Waiver: No failure or delay by a party to exercise any right or remedy provided under this Publication Agreement or by law shall constitute a waiver of that or any other right or remedy, nor shall it preclude or restrict the further exercise of that or any other right or remedy. No single or partial exercise of such right or remedy shall preclude or restrict the further exercise of that or any other right or remedy.
\n\n7.5 Variation: No variation of this Publication Agreement shall be effective unless it is in writing and signed by the parties (or their duly authorized representatives).
\n\n7.6 Severance: If any provision or part-provision of this Publication Agreement is or becomes invalid, illegal or unenforceable, it shall be deemed modified to the minimum extent necessary to make it valid, legal and enforceable. If such modification is not possible, the relevant provision or part-provision shall be deemed deleted.
\n\nAny modification to or deletion of a provision or part-provision under this clause shall not affect the validity and enforceability of the rest of this Publication Agreement.
\n\n7.7 No partnership: Nothing in this Publication Agreement is intended to, or shall be deemed to, establish or create any partnership or joint venture or the relationship of principal and agent or employer and employee between IntechOpen and the Corresponding Author or any Co-Author, nor authorize any party to make or enter into any commitments for or on behalf of any other party.
\n\n7.8 Governing law: This Publication Agreement and any dispute or claim (including non-contractual disputes or claims) arising out of or in connection with it or its subject matter or formation shall be governed by and construed in accordance with the law of England and Wales. The parties submit to the exclusive jurisdiction of the English courts to settle any dispute or claim arising out of or in connection with this Publication Agreement (including any non-contractual disputes or claims).
\n\nLast updated: 2020-11-27
\n\n\n\n
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I am also a member of the team in charge for the supervision of Ph.D. students in the fields of development of silicon based planar waveguide sensor devices, study of inelastic electron tunnelling in planar tunnelling nanostructures for sensing applications and development of organotellurium(IV) compounds for semiconductor applications. I am a specialist in data analysis techniques and nanosurface structure. 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Today his focus is on defining the growth and development strategy for the company.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"19816",title:"Prof.",name:"Alexander",middleName:null,surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/19816/images/1607_n.jpg",biography:"Alexander I. Kokorin: born: 1947, Moscow; DSc., PhD; Principal Research Fellow (Research Professor) of Department of Kinetics and Catalysis, N. Semenov Institute of Chemical Physics, Russian Academy of Sciences, Moscow.\r\nArea of research interests: physical chemistry of complex-organized molecular and nanosized systems, including polymer-metal complexes; the surface of doped oxide semiconductors. He is an expert in structural, absorptive, catalytic and photocatalytic properties, in structural organization and dynamic features of ionic liquids, in magnetic interactions between paramagnetic centers. The author or co-author of 3 books, over 200 articles and reviews in scientific journals and books. He is an actual member of the International EPR/ESR Society, European Society on Quantum Solar Energy Conversion, Moscow House of Scientists, of the Board of Moscow Physical Society.",institutionString:null,institution:{name:"Semenov Institute of Chemical Physics",country:{name:"Russia"}}},{id:"62389",title:"PhD.",name:"Ali Demir",middleName:null,surname:"Sezer",slug:"ali-demir-sezer",fullName:"Ali Demir Sezer",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62389/images/3413_n.jpg",biography:"Dr. Ali Demir Sezer has a Ph.D. from Pharmaceutical Biotechnology at the Faculty of Pharmacy, University of Marmara (Turkey). 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