Click chemistry and drug delivery:A bird's-eye view

Click chemistry has been proven to be very useful in drug delivery.Due to the availability of a large number of click reactions with a various characteristics,selection of appropriate chemistry for a given application is often not a trivial task.This review is written for pharmaceutical researchers who are interested in click chemistry applications and yet may not be click chemistry experts.For this,the review gives an overview of available click reactions organized by application types.Further,the general understanding of click reactions being fast and high yielding sometimes overshadows the need to analyze reaction kinetics in assessing suitability of a given reaction for certain applications.For this,we highlight the need to analyze the relationship among reaction kinetics,concentration effects,and reaction time scales,knowing that lack of such analysis could easily lead to failures.Further,possible issues such as chemical stability with various click reagents are also discussed to aid experimental designs.Recent examples and extensive references are also provided to aid in-depth understanding of technical details.We hope this review will help those interested in using click chemistry in drug delivery to select the appropriate reactions/reagents and minimize the number of pitfalls.

Preface The Sino-US chemistry professors conference:history and outlook

On June 29–30, 2009, the Fifth Sino-US Chemistry Professors Conference, co-organized by Lanzhou University and the Chinese-American Chemistry & Chemical Biology Professors Association (CAPA, USA), was held in Lanzhou. About 150 professors from China, USA and other

Evaluation of the transfer function of human pulse system based on signal detection

On the basis of the pulse source-system model, a convenient and effective method used to evaluate the transfer function of human pulse system has been proposed by using the principle of signal detection and system analysis. The experimental results show that the pulse system of the normal pulse has 3 formants; the smooth pulse, 2 formants; the wiry pulse, 4 formants; and the thready pulse, only 1 formant. Formant frequencies reflect the resonance behaviour of the arterial system.

Hydrogen sulfide prodrugs—a review

Hydrogen sul fi de(H_2S) is recognized as one of three gasotransmitters together with nitric oxide(NO) and carbon monoxide(CO). As a signaling molecule, H_2S plays an important role in physiology and shows great potential in pharmaceutical applications. Along this line, there is a need for the development of H_2S prodrugs for various reasons. In this review, we summarize different H_2S prodrugs, their chemical properties, and some of their potential therapeutic applications.

Nature’s marvels endowed in gaseous molecules Ⅰ:Carbon monoxide and its physiological and therapeutic roles

Nature has endowed gaseous molecules such as O_(2),CO_(2),CO,NO,H2 S,and N2 with critical and diverse roles in sustaining life,from supplying energy needed to power life and building blocks for life ’s physical structure to mediating and coordinating cellular functions.In this article,we give a brief introduction of the complex functions of the various gaseous molecules in life and then focus on carbon monoxide as a specific example of an endogenously produced signaling molecule to highlight the importance of this class of molecules.The past twenty years have seen much progress in understanding CO’s mechanism(s) of action and pharmacological effects as well as in developing delivery methods for easy administration.One remarkable trait of CO is its pleiotropic effects that have few parallels,except perhaps its sister gaseous signaling molecules such as nitric oxide and hydrogen sulfide.This review will delve into the sophistication of CO-mediated signaling as well as its validated pharmacological functions and possible therapeutic applications.

Organic carbon monoxide prodrug, BW-CO-111, in protection against chemically-induced gastric mucosal damage

Metal-based carbon monoxide(CO)-releasing molecules have been shown to exert antiinflammatory and anti-oxidative properties maintaining gastric mucosal integrity.We are interested in further development of metal-free CO-based therapeutics for oral administration.Thus,we examine the protective effect of representative CO prodrug,BW-CO-111.in rat models of gastric damage induced by necrotic ethanol or aspirin,a representative non-steroidal anti-inflammatory drug.Treatment effectiveness was assessed by measuring the microscopic/macroscopic gastric damage area and gastric blood flow by laser flowmetry.Gastric mucosal mRNA and/or protein expressions of HMOX1,HMOX2,nuclear factor erythroid 2-related factor 2,COX1,COX2,iNos,Anxa1 and serum contents of TGFB1,TGFB2,IL1 B,IL2,IL4,IL5,IL6,IL10,IL12,tumor necrosis factorα,interferonγ,and GM-CSF were determined.CO content in gastric mucosa was assessed by gas chromatography.Pretreatment with BW-CO-111(0.1 mg/kg,i.g.)increased gastric mucosal content of CO and reduced gastric lesions area in both models followed by increased GBF.These protective effects of the CO prodrug were supported by changes in expressions of molecular biomarkers.However,because the pathomechanisms of gastric damage differ between topical administration of ethanol and aspirin,the possible protective and anti-inflammatory mechanisms of BW-CO-111 may be somewhat different in these models.